{ "libraryEn": { "v": "4c0646a1", "counts": { "paperSummaries": 864, "trialSummaries": 667, "commentaries": 337, "featured": 15 } }, "site": { "name": "IATHEON", "tagline": "Gastric & Breast Cancer Research", "owner": "RISCON Labs", "built": "2026-09-28", "lang": { "ui": "en", "records": "ko" }, "generated": "2026-11-13", "scaleBundle": "3161e08c" }, "retrieved": { "papers": "2026-10-30", "trials": "2026-10-30", "proteins": "2026-10-05", "structures": "2026-09-28", "indicators": "2026-11-06", "integrity": "2026-11-13", "analyses": "2026-09-28" }, "quality": { "about": "Measured quality of the IATHEON records: random-sample audits, cross-family judge passes with decoy-measured sensitivity, and the corrections they produced. Numbers here are counts from the audit files, not estimates.", "method": [ "Every number in a summary must appear in the stored source (PubMed abstract, saved ClinicalTrials.gov snapshot or saved reference page); the site build fails otherwise.", "Random-sample audits read every sentence of randomly drawn records against the stored sources and grade errors as fatal (a reader would draw a wrong clinical or scientific conclusion), major (an unsupported fact, wrong count or date) or minor (misleading wording).", "Cross-family judge passes run models from a different family than the model that wrote the record. Each pass includes decoys, older versions of records that are known to contain errors, so the share of decoys a judge flags measures how much it catches.", "A judge's flag is not a correction. Every flagged sentence is checked again against the stored source before the record is changed, and the record's byline names the check that changed it.", "Clinical readings are checked on every build: each quote must be the abstract's own words, every number must be in the abstract, and the absolute difference, the number needed to treat or harm and the certainty grade are recomputed by code. A test plants each kind of error and the build must catch all of them." ], "audits": [ { "date": "2026-11-06", "kind": "cross-family judge", "scope": "233 new paper summaries and commentaries", "judges": "Qwen3 235B (batch), Kimi K3.1 Pro", "decoys": 21, "decoysCaught": { "Qwen3 235B": 4, "Kimi K3.1 Pro": 14 }, "flagged": 106, "confirmed": 26, "fatalConfirmed": 0 }, { "date": "2026-11-06", "kind": "cross-family judge", "scope": "279 new trial summaries", "judges": "Kimi K3.1 Pro", "decoys": 0, "flagged": 338, "confirmed": 78, "fatalConfirmed": 1 }, { "date": "2026-11-07", "kind": "random-sample audit", "scope": "60 records (25 paper summaries, 20 trial summaries, 15 commentaries), 773 sentences", "judges": "Claude Opus 5.5 (four independent auditors)", "records": 60, "sentences": 773, "fatal": 3, "major": 28, "minor": 31, "confirmed": 48, "note": "Measured before the fixes. All three fatal errors were in trial summaries; 12 of the major findings were registry facts that became checkable once the missing registry snapshots were stored." }, { "date": "2026-11-07", "kind": "cross-family judge", "scope": "all 667 trial summaries", "judges": "Claude Sonnet 4.6 (batch), Kimi K3.1 Pro, Claude Sonnet 5.5, Gemini 4", "decoys": 25, "decoysCaught": { "Claude Sonnet 4.6": 17, "Gemini 4": 21 }, "flagged": 463, "confirmed": 356, "fatalConfirmed": 9 }, { "date": "2026-11-07", "kind": "cross-family judge", "scope": "124 Korean judgments", "judges": "Claude Sonnet 4.6 (batch)", "decoys": 0, "flagged": 9, "confirmed": 4, "fatalConfirmed": 1 }, { "date": "2026-11-07", "kind": "structural check", "scope": "All 140 clinical readings: 517 quotes and every number", "judges": "Build gate 13 (code)", "decoys": 0, "flagged": 197, "confirmed": 197, "fatalConfirmed": 0, "note": "190 quotes had source notes inside the quotation; the notes now sit beside the verbatim quote. Two English takeaways were vaguer than the abstract (KAITLIN, HER2CLIMB-02) and five confidence levels were unnamed. Rows where the control arm did better now show the number needed to harm." }, { "date": "2026-11-08", "kind": "cross-family judge", "scope": "all 864 paper summaries and 337 commentaries", "judges": "Claude Haiku 5.5 (batch)", "decoys": 25, "decoysCaught": { "Claude Haiku 5.5": 5 }, "flagged": 81, "confirmed": 43, "fatalConfirmed": 0, "note": "Haiku flagged 81 sentences as major or fatal; Claude Opus 5.5 checked each against the stored abstract, registry snapshot and cited sources and fixed 43 (20 major, 23 minor). The most common error was a sentence saying a result was not reported when the stored registry record posts it. Eight more flags were true (six per the live ClinicalTrials.gov record, two per a stored registry record behind a cited summary), so those sentences stay. Haiku caught only 5 of 25 planted errors, so passing this check says little about the records it did not flag." } ], "certaintyRule": { "summary": "IATHEON grades the certainty of the reported primary result of one randomized trial with the GRADE domains that an abstract can show. Each grade starts at high and moves down one level for each concern below; consistency across trials is judged in the commentaries, not here.", "steps": [ "Start at high for a randomized comparison.", "Risk of bias: down one when the abstract states the trial was open-label and the primary endpoint was not overall survival and was not assessed by blinded independent central review.", "Imprecision: down one when the confidence interval of the primary effect includes no effect (1 for a ratio, 0 for a difference), or when no confidence interval is reported.", "Imprecision: down one when fewer than 300 patients were randomized (at most two levels for imprecision in total).", "Indirectness: down one when the primary endpoint is pathological complete response or objective response, which stand in for survival.", "Levels: high, moderate, low, very low. The grade describes the primary result as the abstract reports it; it is not a recommendation." ] }, "coverage": { "units": 348, "unitsWithStoredSource": 348, "clinicalReadings": 139, "clinicalRctUnits": 143, "paperSummaries": 864, "paperSummariesWithAbstract": 864, "paperSummariesLinkedToTrial": 397, "paperSummariesWithSnapshot": 397, "trialSummaries": 667, "trialSummariesWithSnapshot": 667, "commentaries": 337, "pairs": 129, "correctedRecords": 504 } }, "menu": [ { "id": "overview", "label": "Overview", "shortLabel": "Overview", "code": "OVERVIEW", "summary": "Gastric and breast cancer core programmes, the colorectal extension, newest evidence and next checks.", "summary_ko": "위암·유방암 핵심 프로그램과 대장암 확장, 최신 근거와 다음 검증.", "motif": "ONCOLOGY RESEARCH DESK · SOURCE-LINKED EVIDENCE", "items": [ { "id": "desk", "label": "Research Desk", "state": "built", "note": "Landing view: the core gastric and breast cancer programmes, the colorectal extension, current questions, newest evidence and next checks.", "route": "#desk" }, { "id": "mission", "label": "Mission & Priorities", "state": "built", "note": "What the project is for, what it will not claim, and the standing questions.", "route": "#mission" }, { "id": "progress", "label": "Progress", "state": "built", "note": "Counts of what exists, by state. No score.", "route": "#progress" }, { "id": "quality", "label": "Quality Report", "state": "built", "note": "Measured error rates from random-sample audits, cross-family judge passes with decoy-measured sensitivity, source coverage and the corrections they produced.", "route": "#quality" }, { "id": "briefs", "label": "Research Briefs", "state": "built", "note": "Dated research syntheses with study comparisons, linked evidence, uncertainties and next checks.", "route": "#briefs" } ] }, { "id": "forecasting", "label": "Question → Forecast", "shortLabel": "Forecast", "code": "PROGNOSIS", "summary": "Core competency: prospective questions, frozen forecasts recorded before trial readouts, and rigorous result comparison.", "summary_ko": "핵심 역량: 임상시험 결과 공개 전 질문과 예측을 동결하고 엄격하게 결과를 대조합니다.", "motif": "PROSPECTIVE FREEZE · HASH-PINNED PREDICTIONS · ZERO SIGHT OF RESULTS", "items": [ { "id": "workbench", "label": "Research Workbench", "state": "built", "note": "Start a question, link evidence, and write the forecast and its assumptions; research files and drafts saved in this browser are also kept here.", "route": "#workbench" }, { "id": "hypotheses", "label": "Hypothesis Board", "state": "built", "note": "Standing hypotheses with the evidence that would change each one.", "route": "#hypotheses" }, { "id": "forecasts", "label": "Forecast Ledger", "state": "built", "note": "Every frozen forecast with its stage, comparison rules and dated result checks. Incorrect forecasts stay in the ledger.", "route": "#forecasts" }, { "id": "readouts", "label": "Readout Watch", "state": "built", "note": "Registry primary-completion dates and posted-result flags for every trial in the library, with the forecasts and judgments that wait on each.", "route": "#readouts" }, { "id": "review", "label": "Comparison & Review", "state": "built", "note": "Result comparisons, dated checks that found no eligible result, judgment-state changes and reviewed correction notices.", "route": "#review" }, { "id": "roadmap", "label": "Validation Roadmap", "state": "built", "note": "Searchable judgment plans with recorded next checks, review criteria, planning dependencies and links to completed evaluations, plus a filter for held judgments.", "route": "#roadmap" } ] }, { "id": "programs", "label": "Programs", "shortLabel": "Programs", "code": "CLINICAL", "summary": "Core programmes in gastric and breast malignancies, with authorised colorectal and exploratory thyroid collections.", "summary_ko": "위암·유방암 핵심 프로그램과 대장암·갑상선암 확장 연구 수집.", "motif": "ADENOCARCINOMA · HER2 SUBTYPES · RESISTANCE TARGETS", "items": [ { "id": "gastric", "label": "Gastric Cancer", "state": "built", "note": "Core gastric adenocarcinoma research programme: targets, trials and biomarker stratification.", "route": "#program/gastric" }, { "id": "breast", "label": "Breast Cancer", "state": "built", "note": "Core breast cancer research programme: luminal, HER2-low/positive and triple-negative subtypes.", "route": "#program/breast" }, { "id": "colorectal", "label": "Colorectal Cancer", "state": "built", "note": "Searchable, authorised colorectal collection with source records, a research file and linked judgments. Scientific coverage remains partial.", "route": "#program/colorectal" }, { "id": "thyroid", "label": "Thyroid Cancer", "state": "built", "note": "A separate, exploratory thyroid collection that keeps treatment and screening questions apart by driver mutation; scientific coverage remains partial.", "route": "#program/thyroid" }, { "id": "gxb", "label": "Gastric × Breast", "state": "built", "note": "Side-by-side comparison of targets in the two cancers, with the extra evidence needed to carry each finding from one cancer to the other.", "route": "#program/gxb" } ] }, { "id": "discovery", "label": "Discovery", "shortLabel": "Discovery", "code": "DISCOVERY", "summary": "Target and biomarker exploration, biological pathways, and therapeutic modalities across both cancers.", "summary_ko": "두 암종에 걸친 표적 및 바이오마커 탐색, 생물학적 경로와 치료 양식.", "motif": "FIVE-AXIS READINESS · UNBIASED EVIDENCE DOSSIERS", "items": [ { "id": "targets", "label": "Target Atlas", "state": "built", "note": "One research file per target: evidence by cancer, biomarkers, approaches, resistance, open questions, and readiness on five separate axes.", "route": "#targets" }, { "id": "biomarkers", "label": "Biomarker Atlas", "state": "built", "note": "Biomarkers kept separate from targets on purpose, each with its assay and threshold.", "route": "#biomarkers" }, { "id": "pathways", "label": "Pathway Explorer", "state": "built", "note": "Diagrams in which any edge without a curated source is labelled 'background'.", "route": "#pathways" }, { "id": "therapeutics", "label": "Therapeutic Landscape", "state": "built", "note": "Approach classes used across the two cancers.", "route": "#therapeutics" } ] }, { "id": "insilico", "label": "In Silico", "shortLabel": "In Silico", "code": "COMPUTE", "summary": "Computational analyses, AlphaFold structure dossiers, public datasets, and fully reproducible verification scripts.", "summary_ko": "계산 분석 등록부, 알파폴드 구조 분석실, 공개 데이터셋 및 완전 재현 스크립트.", "motif": "REPRODUCIBLE PIPELINES · PDB & ALPHAFOLD DB · RUN AUDITS", "items": [ { "id": "analyses", "label": "Analysis Registry", "state": "built", "note": "Every analysis and cohort evaluation by stage — planned, blocked, executed, reproduced, evaluated — with its plan, inputs and outcome.", "route": "#analyses" }, { "id": "structures", "label": "Structure Lab", "state": "built", "note": "Dossiers reading live values from the structure and prediction APIs.", "route": "#structures" }, { "id": "data", "label": "Public Data Explorer", "state": "built", "note": "Datasets with a connection state, not a wish list.", "route": "#data" }, { "id": "repro", "label": "Reproducibility", "state": "built", "note": "Coverage, paired analysis, cohort evaluations, reproductions and the commands that rebuild every number.", "route": "#repro" } ] }, { "id": "evidence", "label": "Evidence", "shortLabel": "Evidence", "code": "EVIDENCE", "summary": "Clinical trial tracking, literature observatory, resistance mechanisms, and negative findings.", "summary_ko": "임상시험 추적, 문헌 관측소, 내성 아틀라스 및 실패·분할 임상시험 기록.", "motif": "PRIMARY SOURCES ONLY · RETRACTION CHECK · NEGATIVE RESULTS KEPT", "items": [ { "id": "literature", "label": "Literature Observatory", "state": "built", "note": "Every cited paper with its identifier, date and correction status.", "route": "#literature" }, { "id": "trials", "label": "Clinical Trial Radar", "state": "built", "note": "Registry records as fetched, including status and whether results are posted.", "route": "#trials" }, { "id": "papersum", "label": "Paper Summaries", "state": "built", "note": "One English summary per PubMed paper, with every number checked against the saved abstract.", "route": "#papersum" }, { "id": "trialsum", "label": "Trial Summaries", "state": "built", "note": "One English summary per registered trial, written from a saved ClinicalTrials.gov record.", "route": "#trialsum" }, { "id": "resistance", "label": "Resistance Atlas", "state": "built", "note": "Search by mechanism, cancer and target, with source-linked records, a reset option and empty-result states.", "route": "#resistance" }, { "id": "negative", "label": "Negative Findings", "state": "built", "note": "Trials that failed or had mixed results, kept as first-class evidence.", "route": "#negative" }, { "id": "gaps", "label": "Items Needing Review", "state": "built", "note": "Evidence, judgments and data access needing further review.", "route": "#gaps" } ] }, { "id": "library", "label": "Library & Maps", "shortLabel": "Library", "code": "ATLAS", "summary": "Curated evidence units, question–judgment pairs, 2D decision relationship graph, and 3D WebGL scale atlas.", "summary_ko": "정제된 근거 단위, 질문-판단 쌍, 2차원 결정지도 및 3차원 WebGL 스케일 아틀라스.", "motif": "EVIDENCE GRAPH · 185 UNITS · 45 PAIRS · 748 EDGES", "items": [ { "id": "cases", "label": "Case Library", "state": "built", "note": "Evidence units as cards, by kind. No invented patients.", "route": "#cases" }, { "id": "pairs", "label": "Question Pairs", "state": "built", "note": "Korean question–judgment records with basis, objection and next checks; English versions where they exist.", "route": "#pairs" }, { "id": "commentary", "label": "Judgment Commentary", "state": "built", "note": "English research judgments on the units and paper summaries they cite, beside the Korean pairs.", "route": "#commentary" }, { "id": "map", "label": "Decision Map", "state": "built", "note": "2D dot map; edges carry a relation and a source.", "route": "#map" }, { "id": "scale", "label": "Scale Mode", "state": "built", "note": "Molecule → Pathway → Tumour → Cohort → Programme. Evidence reachable at every level.", "route": "#scale" } ] }, { "id": "benchmark", "label": "Benchmark", "shortLabel": "Benchmark", "code": "BENCHMARK", "summary": "Structured comparison against thirty world-leading cancer research institutions and program rankings.", "summary_ko": "세계 30대 암 연구기관과의 정량 비교 및 5대 영역별 프로그램 평가.", "motif": "DERIVED METRICS · INDEPENDENT RETRIEVAL · NO SUMMED SCORE", "items": [ { "id": "bench", "label": "Comparison Set 30", "state": "built", "note": "Thirty institutions with published queries and a retrieval date.", "route": "#bench" }, { "id": "profiles", "label": "Institution Profiles", "state": "built", "note": "Derived counts plus a written reason for inclusion.", "route": "#profiles" }, { "id": "rankings", "label": "Program Rankings", "state": "built", "note": "Five areas ranked separately, never summed.", "route": "#rankings" }, { "id": "position", "label": "RISCON Position", "state": "built", "note": "Entered on the same indicators. Marked Not Assessed, with a note on what would change that.", "route": "#position" }, { "id": "collab", "label": "Collaboration Map", "state": "built", "note": "Search sponsor and collaborator roles in trial registries by institution, trial and programme, with source dates, registry links and institution profiles. No RISCON partnership is claimed.", "route": "#collab" } ] }, { "id": "about", "label": "Methods & About", "shortLabel": "Methods", "code": "METHODS", "summary": "Operational methodology, transparent data sources, audit ledger, and AI research council governance.", "summary_ko": "연구 방법론, 공개 데이터 출처, 연구 검증 원장 및 AI 연구평의회 거버넌스.", "motif": "STANDARDS OF PROOF · SCRIPT LOGS · AUTONOMOUS AGENT ROLES", "items": [ { "id": "methods", "label": "Methodology", "state": "built", "note": "How a claim gets in, how a judgment is recorded, how independence is counted.", "route": "#methods" }, { "id": "sources", "label": "Data Sources", "state": "built", "note": "Every API and page, with the exact query and the retrieval date.", "route": "#sources" }, { "id": "ledger", "label": "Research Ledger", "state": "built", "note": "What was checked, when, and by which script.", "route": "#ledger" }, { "id": "council", "label": "AI Research Council", "state": "built", "note": "The nine roles with what actually ran and what did not.", "route": "#council" }, { "id": "riscon", "label": "About RISCON Labs", "state": "built", "note": "The lab's own page at risconlabs.com, in the language you are reading.", "route": "https://risconlabs.com/" } ] } ], "extras": [ { "id": "X-MIND", "label": "What Would Change Our Mind?", "state": "built", "note": "Every pair records the condition that would change it, and the hypothesis board indexes these conditions." }, { "id": "X-NEXT", "label": "Next Best Research Action", "state": "partial", "note": "Derived from the judgments that rest on a single calculation or a single institution. Items are ordered by a stated rule, not by a model." }, { "id": "X-READY", "label": "Target Readiness Profile", "state": "built", "note": "Five axes shown separately: disease relevance, structure, function, clinical, known limits." }, { "id": "X-CONTRA", "label": "Contradiction Board", "state": "built", "note": "Conflicting pairs with the four differences that must be checked first." }, { "id": "X-RECUR", "label": "Recurrence & Metastasis", "state": "partial", "note": "An initial library on recurrence and residual disease has been curated; tumour-specific coverage, external validation and research files remain incomplete." }, { "id": "X-COMBO", "label": "Combination Rationale", "state": "partial", "note": "Combination trials have been curated, but no view comparing rationale with results has been built." }, { "id": "X-REPL", "label": "Replication Queue", "state": "built", "note": "Generated from the claims this library cites as its own (QP-05)." }, { "id": "X-RES", "label": "Research Resource Planner", "state": "planned", "note": "Not built. Only the five gap actions carry an effort label." }, { "id": "X-COLLAB", "label": "Collaboration Map", "state": "built", "note": "Searchable registry roles with source dates, institution profiles and trial links; no RISCON partnership claim." }, { "id": "X-HIST", "label": "Decision History", "state": "partial", "note": "Every judgment carries an asOf date and a change condition; no judgment has been revised yet, so each judgment's history has only one row." } ], "metrics": [ { "id": "M-PATIENT", "label": "Patient records analysed", "how": "verified selected patient identifiers, deduplicated within each study; global cross-study donor identity unverified", "kind": "count" }, { "id": "M-STUDY", "label": "Study datasets analysed", "how": "distinct source study datasets contributing verified patient records", "kind": "count" }, { "id": "M-SRC", "label": "Cited identifiers re-fetched from source", "how": "papers + trials + proteins + structures in data/sources", "kind": "count" }, { "id": "M-INT", "label": "Retraction and duplicate check", "how": "integrity.json: retractions, expressions of concern, duplicate ids", "kind": "state" }, { "id": "M-ERR", "label": "Corrections found and still unreviewed", "how": "integrity.json errata with reviewed = false", "kind": "count" }, { "id": "M-RUN", "label": "Analyses executed, not described", "how": "registered analysis outputs with verified artifact hashes", "kind": "count" }, { "id": "M-COMP", "label": "Analyses computationally reproduced", "how": "unique analyses passing complete comparison and input/code/output hash checks", "kind": "count" }, { "id": "M-COHORT", "label": "External-cohort evaluations completed", "how": "unique completed prespecified patient-cohort evaluations, with supported, opposite-direction and inconclusive outcomes counted separately", "kind": "count" }, { "id": "M-HELD", "label": "Judgments held rather than concluded", "how": "pairs whose judgment states a hold", "kind": "count" }, { "id": "M-REJ", "label": "Hypotheses rejected or revised", "how": "pairs with a recorded revision", "kind": "count" }, { "id": "M-GAP", "label": "Items needing review", "how": "derived review entries; the same question may appear for more than one reason", "kind": "count" }, { "id": "M-NEG", "label": "Negative or mixed evidence units kept", "how": "units with result negative or mixed", "kind": "count" }, { "id": "M-NC", "label": "Features waiting on access or terms", "how": "features and datasets in state not-connected", "kind": "count" } ], "counts": { "evidence": 348, "byResult": { "positive": 132, "descriptive": 122, "negative": 40, "mixed": 54 }, "byLevel": { "clinical": 274, "literature": 20, "computational": 21, "preclinical": 33 }, "byProgram": { "gastric": 89, "expansion": 1, "breast": 144, "method": 6, "structure": 5, "data": 4, "gxb": 2, "colorectal": 49, "thyroid": 48 }, "predictionRecords": 6, "predictionComparisons": 0, "targets": 12, "biomarkers": 19, "pairs": 129, "briefs": 13, "dossiers": 4, "papers": 1314, "trials": 199, "proteins": 33, "structures": 21, "identifiers": 1567, "institutions": 30, "analysesExecuted": 8, "computationalReproduced": 2, "patientRecords": 21479, "studyDatasets": 18, "cohortEvaluated": 12, "cohortSupported": 6, "cohortOpposite": 0, "cohortInconclusive": 6, "replicated": 0, "corrections": 108, "correctionsUnreviewed": 66, "retractions": 0, "gaps": 118, "held": 113, "revised": 0, "datasetsConnected": 15, "datasetsNotConnected": 1, "featuresBuilt": 46, "featuresTotal": 46, "mapNodes": 536, "mapEdges": 1390 }, "researchProgramme": { "version": 1, "asOf": "2026-09-30", "owner": "RISCON Labs", "mission": { "en": "A continuing RISCON Labs programme to discover and validate treatment approaches that could contribute to curing gastric and breast cancer, with an authorised colorectal extension. Finishing the website or enlarging the library does not, on its own, complete this research.", "ko": "위암·유방암의 완치에 기여할 치료 접근을 발견하고 검증하기 위한 RISCON Labs의 지속 연구이며, 승인된 대장·직장암 확장을 포함한다. 사이트 완성이나 자료 증가만으로 이 연구를 완료하지 않는다." }, "scope": { "core": [ "gastric", "breast" ], "extensions": [ "colorectal" ], "summary": { "en": "Gastric and breast cancer remain the core programmes. Colorectal research starts with residual disease, mismatch repair deficiency, response durability and organ preservation. Existing thyroid records form a separate exploratory collection, apart from the core programmes and the authorised colorectal extension. Programmes for other cancers require an explicit decision.", "ko": "위암과 유방암을 핵심 연구축으로 유지한다. 대장·직장암은 잔존 질환, 불일치 복구 결핍, 반응의 지속성, 장기 보존부터 시작한다. 기존 갑상선암 기록은 주 연구나 대장암 확장과 별도의 탐색 자료로 둔다. 다른 암종의 프로그램 확장은 명시적인 결정 뒤 진행한다." } }, "successCriteria": [ { "id": "S-REPRO", "label": { "en": "Independent computational replication", "ko": "독립적인 계산 재현" }, "definition": { "en": "A prespecified question is evaluated with frozen inputs and an independent, held-out biological cohort; the same patients or cell lines re-measured on another platform are not counted twice as independent subjects.", "ko": "사전 정의한 질문을 고정된 입력과 별도 생물학적 검증군에서 평가한다. 같은 환자나 세포주를 다른 플랫폼에서 다시 측정한 자료는 독립 대상으로 두 번 세지 않는다." }, "status": "not_evaluated" }, { "id": "S-BIO", "label": { "en": "External biological validation", "ko": "외부 생물학적 검증" }, "definition": { "en": "A qualified external laboratory tests a supported hypothesis with appropriate controls; a literature claim or simulation alone does not satisfy this stage.", "ko": "적절한 대조군을 갖춘 검증을 외부 전문 실험기관에서 수행한다. 문헌 주장이나 시뮬레이션만으로 이 단계가 충족되지는 않는다." }, "status": "not_evaluated" }, { "id": "S-CLIN", "label": { "en": "Clinically validated benefit", "ko": "임상적으로 검증된 이득" }, "definition": { "en": "Treatment benefit, harms and durable outcomes must be established in an appropriate clinical setting. Response, clearance of the residual signal and a period without recurrence are not automatically called a cure.", "ko": "적절한 임상 맥락에서 치료 이득·위해·지속성을 확인해야 한다. 반응, 잔존 신호 소실, 일정 기간의 무재발을 자동으로 완치라 부르지 않는다." }, "status": "not_evaluated" } ], "capabilities": [ { "id": "CAP-SOURCE", "claim": { "en": "New evidence batches are tied to fetched source records and checked before acceptance.", "ko": "새 근거 배치는 받아 둔 원출처 기록과 연결하고 수록 전에 검사한다." }, "status": "documented_internal", "evidence": [ { "label": { "en": "Methods and source boundaries", "ko": "방법론과 출처 범위" }, "href": "#methods" } ], "validation": { "en": "This is an internally documented process, not a measured advantage over other research groups. Even when a check confirms that a number appears in the source, its context is reviewed separately.", "ko": "이는 내부에서 확인한 운영 방식이며 다른 연구팀보다 우수하다는 비교 결과는 아니다. 숫자 존재 검사를 통과해도 수치의 맥락을 따로 검토한다." } }, { "id": "CAP-CODE", "claim": { "en": "Public-data analyses have saved code and recorded outputs.", "ko": "공개 데이터 분석의 실행 코드와 결과를 보관한다." }, "status": "documented_internal", "evidence": [ { "label": { "en": "Reproducibility record", "ko": "재현성 기록" }, "href": "#repro" } ], "validation": { "en": "A1 and A3 were recalculated with separate Python code on newly frozen official inputs and checked against the original results. Whether the new inputs are byte-identical to the original raw inputs has not been verified. Internal computational reproduction is distinct from held-out biological validation and clinical prediction. An evaluation of the direction of the A1 observation in a separate public patient cohort is recorded on the Reproducibility screen, together with its assay and sample-size limits. It is not a new experiment and does not establish predictive accuracy.", "ko": "A1·A3는 새로 고정한 공식 입력을 별도 Python 코드로 계산해 원래 결과와 대조했다. 과거 원시 입력과 바이트 단위로 같은지는 미확인이다. 내부 계산 재현은 별도 생물학적 검증·임상 예측과 구별한다. A1 관찰의 방향을 별도 공개 환자 코호트에서 평가한 기록과 측정법·표본 한계는 재현성 화면에 남겼다. 새 실험이나 예측 정확도를 입증한 것은 아니다." } }, { "id": "CAP-DECISION", "claim": { "en": "Each research judgment is recorded with its counterarguments and the evidence that would change it.", "ko": "연구 판단에 반론과 판단을 바꿀 근거를 함께 남긴다." }, "status": "documented_internal", "evidence": [ { "label": { "en": "Question and judgment records", "ko": "질문·판단 기록" }, "href": "#pairs" } ], "validation": { "en": "Accumulated decisions may become a useful research asset. Their effect on decision quality has not yet been measured against a baseline.", "ko": "축적된 판단 기록은 연구 자산이 될 수 있다. 실제 판단의 질을 높이는지는 비교 기준을 두고 아직 측정하지 않았다." } }, { "id": "CAP-ADVANTAGE", "claim": { "en": "Hypothesis: an audited, cross-cancer evidence-and-refutation history can improve the quality of follow-up research choices.", "ko": "가설: 감사 가능한 암종 간 근거·반증 이력이 후속 연구 선택의 질을 높일 수 있다." }, "status": "unvalidated", "evidence": [ { "label": { "en": "Validation roadmap", "ko": "검증 로드맵" }, "href": "#roadmap" } ], "validation": { "en": "On a frozen set of research questions, compare work done with this curated history against work done with the same tools but without it, assessing source errors by blinded review, independent reproducibility and time to a reviewable result. Do not claim uniqueness, superior accuracy or clinical efficacy before that comparison.", "ko": "같은 도구를 쓰되 축적된 이력이 없는 조건과 고정된 연구 질문을 비교한다. 출처 오류의 눈가림 검토, 독립 재현, 검토 가능한 결과까지의 시간을 평가한다. 비교 전에는 유일성·정확도 우위·임상 효능을 주장하지 않는다." } } ], "questions": [ { "id": "RQ-ERBB2-CCNE1", "program": "gxb", "question": { "en": "Within gastric and breast cancer models separately, is CCNE1 copy number associated with ERBB2 dependency after accounting for ERBB2 copy number?", "ko": "위암·유방암 모델 각각에서 ERBB2 복제수를 고려한 뒤에도 CCNE1 복제수에 따라 ERBB2 의존성이 다른가" }, "status": "blocked_access", "next": { "en": "Obtain the remaining pinned DepMap 24Q4 v1 inputs through a permitted download path, verify their hashes and profile/culture mapping, then complete and lock the analysis plan before reading outcomes.", "ko": "허용된 경로로 DepMap 24Q4 v1의 남은 파일을 받고 해시·프로필·배양 조건의 연결을 확인한 뒤, 결과를 열기 전에 분석계획을 확정한다." }, "limits": { "en": "Only 1 of 5 required data files has been verified. Checking metadata is not the same as running the analysis. No dependency regression or drug-response analysis has been run, and a CRISPR knockout is not the same as a patient's response to treatment.", "ko": "필수 자료 5개 중 1개만 수신·검증했다. 메타데이터 확인은 분석 실행이 아니다. 의존성 회귀·약물반응 분석은 실행하지 않았으며 CRISPR 유전자 제거는 환자의 치료 반응과 다르다." }, "accessCheckId": "ACCESS-A4-20260930" }, { "id": "RQ-ESR1-CONTEXT", "program": "breast", "question": { "en": "Does the ESR1 difference between primary and metastatic samples persist after patient overlap and differences in treatment history are accounted for?", "ko": "환자 중복과 치료이력 차이를 확인한 뒤에도 원발·전이 표본의 ESR1 차이가 유지되는가" }, "status": "planned", "next": { "en": "Audit patient identifiers, sample relationships and available treatment fields before a confirmatory analysis.", "ko": "확증 분석 전에 환자 식별자, 반복 표본 관계, 이용 가능한 치료이력 필드를 점검한다." }, "limits": { "en": "The existing A2 analysis is cross-sectional and does not estimate the effect of a treatment or a mutation on survival.", "ko": "기존 A2는 단면 비교이며 치료나 변이가 생존에 미치는 효과를 추정하지 않는다." } }, { "id": "RQ-CRC-MRD", "program": "colorectal", "question": { "en": "Which colorectal MRD-guided strategies have demonstrated clinical utility, and which findings remain prognostic associations?", "ko": "대장·직장암 잔존 질환 검사 기반 전략 중 임상적 유용성을 보인 것과 예후 연관성에 머문 것은 무엇인가" }, "status": "planned", "next": { "en": "Compare study populations, decision rules, randomisation, assay timing and recurrence outcomes before proposing a scenario model.", "ko": "가정 기반 모형을 만들기 전에 대상군·의사결정 규칙·무작위 배정·검사 시점·재발 결과를 비교한다." }, "limits": { "en": "A trial in stage II colon cancer does not validate a strategy in rectal, gastric or breast cancer.", "ko": "2기 결장암 연구가 직장암·위암·유방암의 전략을 검증해 주지는 않는다." } } ], "simulationPolicy": { "en": "Keep observed-data analysis, assumption-based scenario simulation and externally validated prediction separate. Register the question, inputs, assumptions, code, validation split and stopping rules before a run. Keep the planned, awaiting-access and executed states distinct, and do not treat a score or agreement among AI models as evidence of treatment efficacy.", "ko": "관측 데이터 분석, 가정 기반 시나리오 시뮬레이션, 외부 검증된 예측을 구분한다. 실행 전에 질문·입력·가정·코드·검증 분리·중단 기준을 등록한다. 계획·접근 대기·실행 상태를 구별하며, 점수나 여러 AI의 동의를 치료 효능으로 바꾸지 않는다." } }, "researchRecords": { "executions": [ { "analysisId": "A1", "kind": "legacy-recorded-output", "date": "2026-09-28", "output": { "path": "data/analyses/A1-erbb2-amplification.json", "sha256": "c83954d7abd4d4acead4ae726dae486961e55759ed644032985b60d7017e5221" }, "implementation": { "path": "scripts/run-analyses.mjs", "sha256": "24fb246a5ea1d9a3a2f7f352195596767e7001011b1132f631eafb5e1ee94dec" } }, { "analysisId": "A2", "kind": "legacy-recorded-output", "date": "2026-09-28", "output": { "path": "data/analyses/A2-esr1-pik3ca-primary-vs-metastatic.json", "sha256": "781a9ec61cf32a9ee24ee85529741f9fb22325ea9b0ee1c89a245e2625af9d83" }, "implementation": { "path": "scripts/run-analyses.mjs", 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genes were re-fetched. The original run did not retain raw-input hashes; byte-identical historical input is not established." }, "implementation": { "script": "scripts/reproduce-a1.py", "sha256": "c08236f469d10accfb4d78c458beea40f1821c87f987eabfb528daac54378da2", "language": "Python", "version": "3.13.5", "author": "Codex (GPT-6)", "method": "Validate a complete sample-by-gene matrix; derive amplification sets, set intersections and selected-gene union; Decimal rounding." }, "comparison": { "passed": true, "checkedFields": 84, "failedFields": 0, "originalHashMatches": true, "checks": [ { "expectedPath": "/results/0/study", "actualPath": "/results/0/study", "expected": "stad_tcga_pan_can_atlas_2018", "actual": "stad_tcga_pan_can_atlas_2018", "pass": true }, { "expectedPath": "/results/0/sampleList", "actualPath": "/results/0/sampleList", "expected": "stad_tcga_pan_can_atlas_2018_cna", "actual": "stad_tcga_pan_can_atlas_2018_cna", "pass": true }, { "expectedPath": "/results/0/profile", "actualPath": "/results/0/profile", "expected": "stad_tcga_pan_can_atlas_2018_gistic", "actual": "stad_tcga_pan_can_atlas_2018_gistic", "pass": true }, { "expectedPath": "/results/0/samples", "actualPath": "/results/0/samples", "expected": 438, "actual": 438, "pass": true }, { "expectedPath": "/results/0/erbb2Amplified", "actualPath": "/results/0/erbb2Amplified", "expected": 58, "actual": 58, "pass": true }, { "expectedPath": "/results/0/genes/ERBB2/amplified", "actualPath": "/results/0/genes/ERBB2/amplified", "expected": 58, "actual": 58, "pass": true }, { "expectedPath": "/results/0/genes/ERBB2/pct", "actualPath": "/results/0/genes/ERBB2/pct", "expected": 13.2, "actual": 13.2, "pass": true }, { "expectedPath": "/results/0/genes/GRB7/amplified", "actualPath": "/results/0/genes/GRB7/amplified", "expected": 58, "actual": 58, "pass": true }, { "expectedPath": "/results/0/genes/GRB7/pct", "actualPath": "/results/0/genes/GRB7/pct", "expected": 13.2, "actual": 13.2, "pass": true }, { "expectedPath": "/results/0/genes/GRB7/withERBB2", "actualPath": "/results/0/genes/GRB7/withERBB2", "expected": 58, "actual": 58, "pass": true }, { "expectedPath": "/results/0/genes/GRB7/pctOfERBB2amp", "actualPath": "/results/0/genes/GRB7/pctOfERBB2amp", "expected": 100, "actual": 100, "pass": true }, { "expectedPath": "/results/0/genes/CDK12/amplified", "actualPath": "/results/0/genes/CDK12/amplified", "expected": 39, "actual": 39, "pass": true }, { "expectedPath": "/results/0/genes/CDK12/pct", "actualPath": "/results/0/genes/CDK12/pct", "expected": 8.9, "actual": 8.9, "pass": true }, { "expectedPath": "/results/0/genes/CDK12/withERBB2", "actualPath": "/results/0/genes/CDK12/withERBB2", "expected": 39, "actual": 39, "pass": true }, { "expectedPath": "/results/0/genes/CDK12/pctOfERBB2amp", "actualPath": "/results/0/genes/CDK12/pctOfERBB2amp", "expected": 67.2, "actual": 67.2, "pass": true }, { "expectedPath": "/results/0/genes/EGFR/amplified", "actualPath": "/results/0/genes/EGFR/amplified", "expected": 23, "actual": 23, "pass": true }, { "expectedPath": "/results/0/genes/EGFR/pct", "actualPath": "/results/0/genes/EGFR/pct", "expected": 5.3, "actual": 5.3, "pass": true }, { "expectedPath": "/results/0/genes/EGFR/withERBB2", "actualPath": "/results/0/genes/EGFR/withERBB2", "expected": 4, "actual": 4, "pass": true }, { "expectedPath": "/results/0/genes/EGFR/pctOfERBB2amp", "actualPath": "/results/0/genes/EGFR/pctOfERBB2amp", "expected": 6.9, "actual": 6.9, "pass": true }, { "expectedPath": "/results/0/genes/MET/amplified", "actualPath": "/results/0/genes/MET/amplified", "expected": 12, "actual": 12, "pass": true }, { "expectedPath": "/results/0/genes/MET/pct", "actualPath": "/results/0/genes/MET/pct", "expected": 2.7, "actual": 2.7, "pass": true }, { "expectedPath": "/results/0/genes/MET/withERBB2", "actualPath": "/results/0/genes/MET/withERBB2", "expected": 3, "actual": 3, "pass": true }, { "expectedPath": "/results/0/genes/MET/pctOfERBB2amp", "actualPath": "/results/0/genes/MET/pctOfERBB2amp", "expected": 5.2, "actual": 5.2, "pass": true }, { "expectedPath": "/results/0/genes/FGFR2/amplified", "actualPath": "/results/0/genes/FGFR2/amplified", "expected": 19, "actual": 19, "pass": true }, { "expectedPath": "/results/0/genes/FGFR2/pct", "actualPath": "/results/0/genes/FGFR2/pct", "expected": 4.3, "actual": 4.3, "pass": true }, { "expectedPath": "/results/0/genes/FGFR2/withERBB2", "actualPath": "/results/0/genes/FGFR2/withERBB2", "expected": 4, "actual": 4, "pass": true }, { "expectedPath": "/results/0/genes/FGFR2/pctOfERBB2amp", "actualPath": "/results/0/genes/FGFR2/pctOfERBB2amp", "expected": 6.9, "actual": 6.9, "pass": true }, { "expectedPath": "/results/0/genes/KRAS/amplified", "actualPath": "/results/0/genes/KRAS/amplified", "expected": 35, "actual": 35, "pass": true }, { "expectedPath": "/results/0/genes/KRAS/pct", "actualPath": "/results/0/genes/KRAS/pct", "expected": 8, "actual": 8, "pass": true }, { "expectedPath": "/results/0/genes/KRAS/withERBB2", "actualPath": "/results/0/genes/KRAS/withERBB2", "expected": 2, "actual": 2, "pass": true }, { "expectedPath": "/results/0/genes/KRAS/pctOfERBB2amp", "actualPath": "/results/0/genes/KRAS/pctOfERBB2amp", "expected": 3.4, "actual": 3.4, "pass": true }, { "expectedPath": "/results/0/genes/CCNE1/amplified", "actualPath": "/results/0/genes/CCNE1/amplified", "expected": 49, "actual": 49, "pass": true }, { "expectedPath": "/results/0/genes/CCNE1/pct", "actualPath": "/results/0/genes/CCNE1/pct", "expected": 11.2, "actual": 11.2, "pass": true }, { "expectedPath": "/results/0/genes/CCNE1/withERBB2", "actualPath": "/results/0/genes/CCNE1/withERBB2", "expected": 18, "actual": 18, "pass": true }, { "expectedPath": "/results/0/genes/CCNE1/pctOfERBB2amp", "actualPath": "/results/0/genes/CCNE1/pctOfERBB2amp", "expected": 31, "actual": 31, "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/genes/0", "actualPath": "/results/0/erbb2WithAnyOf/genes/0", "expected": "EGFR", "actual": "EGFR", "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/genes/1", "actualPath": "/results/0/erbb2WithAnyOf/genes/1", "expected": "MET", "actual": "MET", "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/genes/2", "actualPath": "/results/0/erbb2WithAnyOf/genes/2", "expected": "FGFR2", "actual": "FGFR2", "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/genes/3", "actualPath": "/results/0/erbb2WithAnyOf/genes/3", "expected": "KRAS", "actual": "KRAS", "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/genes/4", "actualPath": "/results/0/erbb2WithAnyOf/genes/4", "expected": "CCNE1", "actual": "CCNE1", "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/n", "actualPath": "/results/0/erbb2WithAnyOf/n", "expected": 27, "actual": 27, "pass": true }, { "expectedPath": "/results/0/erbb2WithAnyOf/pct", "actualPath": "/results/0/erbb2WithAnyOf/pct", "expected": 46.6, "actual": 46.6, "pass": true }, { "expectedPath": "/results/1/study", "actualPath": "/results/1/study", "expected": "brca_tcga_pan_can_atlas_2018", "actual": "brca_tcga_pan_can_atlas_2018", "pass": true }, { "expectedPath": "/results/1/sampleList", "actualPath": "/results/1/sampleList", "expected": "brca_tcga_pan_can_atlas_2018_cna", "actual": "brca_tcga_pan_can_atlas_2018_cna", "pass": true }, { "expectedPath": "/results/1/profile", "actualPath": "/results/1/profile", "expected": "brca_tcga_pan_can_atlas_2018_gistic", "actual": "brca_tcga_pan_can_atlas_2018_gistic", "pass": true }, { "expectedPath": "/results/1/samples", "actualPath": "/results/1/samples", "expected": 1070, "actual": 1070, "pass": true }, { "expectedPath": "/results/1/erbb2Amplified", "actualPath": "/results/1/erbb2Amplified", "expected": 123, "actual": 123, "pass": true }, { "expectedPath": "/results/1/genes/ERBB2/amplified", "actualPath": "/results/1/genes/ERBB2/amplified", "expected": 123, "actual": 123, "pass": true }, { "expectedPath": "/results/1/genes/ERBB2/pct", "actualPath": "/results/1/genes/ERBB2/pct", "expected": 11.5, "actual": 11.5, "pass": true }, { "expectedPath": "/results/1/genes/GRB7/amplified", "actualPath": "/results/1/genes/GRB7/amplified", "expected": 122, "actual": 122, "pass": true }, { "expectedPath": "/results/1/genes/GRB7/pct", "actualPath": "/results/1/genes/GRB7/pct", "expected": 11.4, "actual": 11.4, "pass": true }, { "expectedPath": "/results/1/genes/GRB7/withERBB2", "actualPath": "/results/1/genes/GRB7/withERBB2", "expected": 122, "actual": 122, "pass": true }, { "expectedPath": "/results/1/genes/GRB7/pctOfERBB2amp", "actualPath": "/results/1/genes/GRB7/pctOfERBB2amp", "expected": 99.2, "actual": 99.2, "pass": true }, { "expectedPath": "/results/1/genes/CDK12/amplified", "actualPath": "/results/1/genes/CDK12/amplified", "expected": 111, "actual": 111, "pass": true }, { "expectedPath": "/results/1/genes/CDK12/pct", "actualPath": "/results/1/genes/CDK12/pct", "expected": 10.4, "actual": 10.4, "pass": true }, { "expectedPath": "/results/1/genes/CDK12/withERBB2", "actualPath": "/results/1/genes/CDK12/withERBB2", "expected": 109, "actual": 109, "pass": true }, { "expectedPath": "/results/1/genes/CDK12/pctOfERBB2amp", "actualPath": "/results/1/genes/CDK12/pctOfERBB2amp", "expected": 88.6, "actual": 88.6, "pass": true }, { "expectedPath": "/results/1/genes/EGFR/amplified", "actualPath": "/results/1/genes/EGFR/amplified", "expected": 17, "actual": 17, "pass": true }, { "expectedPath": "/results/1/genes/EGFR/pct", "actualPath": "/results/1/genes/EGFR/pct", "expected": 1.6, "actual": 1.6, "pass": true }, { "expectedPath": "/results/1/genes/EGFR/withERBB2", "actualPath": "/results/1/genes/EGFR/withERBB2", "expected": 2, "actual": 2, "pass": true }, { "expectedPath": "/results/1/genes/EGFR/pctOfERBB2amp", "actualPath": "/results/1/genes/EGFR/pctOfERBB2amp", "expected": 1.6, "actual": 1.6, "pass": true }, { "expectedPath": "/results/1/genes/MET/amplified", "actualPath": "/results/1/genes/MET/amplified", "expected": 4, "actual": 4, "pass": true }, { "expectedPath": "/results/1/genes/MET/pct", "actualPath": "/results/1/genes/MET/pct", "expected": 0.4, "actual": 0.4, "pass": true }, { "expectedPath": "/results/1/genes/MET/withERBB2", "actualPath": "/results/1/genes/MET/withERBB2", "expected": 0, "actual": 0, "pass": true }, { "expectedPath": "/results/1/genes/MET/pctOfERBB2amp", "actualPath": "/results/1/genes/MET/pctOfERBB2amp", "expected": 0, "actual": 0, "pass": true }, { "expectedPath": "/results/1/genes/FGFR2/amplified", "actualPath": "/results/1/genes/FGFR2/amplified", "expected": 16, "actual": 16, "pass": true }, { "expectedPath": "/results/1/genes/FGFR2/pct", "actualPath": "/results/1/genes/FGFR2/pct", "expected": 1.5, "actual": 1.5, "pass": true }, { "expectedPath": "/results/1/genes/FGFR2/withERBB2", "actualPath": "/results/1/genes/FGFR2/withERBB2", "expected": 2, "actual": 2, "pass": true }, { "expectedPath": "/results/1/genes/FGFR2/pctOfERBB2amp", "actualPath": "/results/1/genes/FGFR2/pctOfERBB2amp", "expected": 1.6, "actual": 1.6, "pass": true }, { "expectedPath": "/results/1/genes/KRAS/amplified", "actualPath": "/results/1/genes/KRAS/amplified", "expected": 15, "actual": 15, "pass": true }, { "expectedPath": "/results/1/genes/KRAS/pct", "actualPath": "/results/1/genes/KRAS/pct", "expected": 1.4, "actual": 1.4, "pass": true }, { "expectedPath": "/results/1/genes/KRAS/withERBB2", "actualPath": "/results/1/genes/KRAS/withERBB2", "expected": 2, "actual": 2, "pass": true }, { "expectedPath": "/results/1/genes/KRAS/pctOfERBB2amp", "actualPath": "/results/1/genes/KRAS/pctOfERBB2amp", "expected": 1.6, "actual": 1.6, "pass": true }, { "expectedPath": "/results/1/genes/CCNE1/amplified", "actualPath": "/results/1/genes/CCNE1/amplified", "expected": 33, "actual": 33, "pass": true }, { "expectedPath": "/results/1/genes/CCNE1/pct", "actualPath": "/results/1/genes/CCNE1/pct", "expected": 3.1, "actual": 3.1, "pass": true }, { "expectedPath": "/results/1/genes/CCNE1/withERBB2", "actualPath": "/results/1/genes/CCNE1/withERBB2", "expected": 4, "actual": 4, "pass": true }, { "expectedPath": "/results/1/genes/CCNE1/pctOfERBB2amp", "actualPath": "/results/1/genes/CCNE1/pctOfERBB2amp", "expected": 3.3, "actual": 3.3, "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/genes/0", "actualPath": "/results/1/erbb2WithAnyOf/genes/0", "expected": "EGFR", "actual": "EGFR", "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/genes/1", "actualPath": "/results/1/erbb2WithAnyOf/genes/1", "expected": "MET", "actual": "MET", "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/genes/2", "actualPath": "/results/1/erbb2WithAnyOf/genes/2", "expected": "FGFR2", "actual": "FGFR2", "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/genes/3", "actualPath": "/results/1/erbb2WithAnyOf/genes/3", "expected": "KRAS", "actual": "KRAS", "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/genes/4", "actualPath": "/results/1/erbb2WithAnyOf/genes/4", "expected": "CCNE1", "actual": "CCNE1", "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/n", "actualPath": "/results/1/erbb2WithAnyOf/n", "expected": 9, "actual": 9, "pass": true }, { "expectedPath": "/results/1/erbb2WithAnyOf/pct", "actualPath": "/results/1/erbb2WithAnyOf/pct", "expected": 7.3, "actual": 7.3, "pass": true } ] }, "computed": { "results": [ { "study": "stad_tcga_pan_can_atlas_2018", "sampleList": "stad_tcga_pan_can_atlas_2018_cna", "profile": "stad_tcga_pan_can_atlas_2018_gistic", "samples": 438, "erbb2Amplified": 58, "genes": { "ERBB2": { "amplified": 58, "pct": 13.2 }, "GRB7": { "amplified": 58, "pct": 13.2, "withERBB2": 58, "pctOfERBB2amp": 100 }, "CDK12": { "amplified": 39, "pct": 8.9, "withERBB2": 39, "pctOfERBB2amp": 67.2 }, "EGFR": { "amplified": 23, "pct": 5.3, "withERBB2": 4, "pctOfERBB2amp": 6.9 }, "MET": { "amplified": 12, "pct": 2.7, "withERBB2": 3, "pctOfERBB2amp": 5.2 }, "FGFR2": { "amplified": 19, "pct": 4.3, "withERBB2": 4, "pctOfERBB2amp": 6.9 }, "KRAS": { "amplified": 35, "pct": 8, "withERBB2": 2, "pctOfERBB2amp": 3.4 }, "CCNE1": { "amplified": 49, "pct": 11.2, "withERBB2": 18, "pctOfERBB2amp": 31 } }, "erbb2WithAnyOf": { "genes": [ "EGFR", "MET", "FGFR2", "KRAS", "CCNE1" ], "n": 27, "pct": 46.6 } }, { "study": "brca_tcga_pan_can_atlas_2018", "sampleList": "brca_tcga_pan_can_atlas_2018_cna", "profile": "brca_tcga_pan_can_atlas_2018_gistic", "samples": 1070, "erbb2Amplified": 123, "genes": { "ERBB2": { "amplified": 123, "pct": 11.5 }, "GRB7": { "amplified": 122, "pct": 11.4, "withERBB2": 122, "pctOfERBB2amp": 99.2 }, "CDK12": { "amplified": 111, "pct": 10.4, "withERBB2": 109, "pctOfERBB2amp": 88.6 }, "EGFR": { "amplified": 17, "pct": 1.6, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "MET": { "amplified": 4, "pct": 0.4, "withERBB2": 0, "pctOfERBB2amp": 0 }, "FGFR2": { "amplified": 16, "pct": 1.5, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "KRAS": { "amplified": 15, "pct": 1.4, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "CCNE1": { "amplified": 33, "pct": 3.1, "withERBB2": 4, "pctOfERBB2amp": 3.3 } }, "erbb2WithAnyOf": { "genes": [ "EGFR", "MET", "FGFR2", "KRAS", "CCNE1" ], "n": 9, "pct": 7.3 } } ] }, "dataQuality": [ { "study": "stad_tcga_pan_can_atlas_2018", "inputRows": 3504, "uniqueSamples": 438, "genes": 8, "expectedCells": 3504, "observedCells": 3504, "duplicateCells": 0, "missingCells": 0, "invalidCalls": 0, "allRowsCorrectStudyAndProfile": true, "allGeneSymbolsVerified": true }, { "study": "brca_tcga_pan_can_atlas_2018", "inputRows": 8560, "uniqueSamples": 1070, "genes": 8, "expectedCells": 8560, "observedCells": 8560, "duplicateCells": 0, "missingCells": 0, "invalidCalls": 0, "allRowsCorrectStudyAndProfile": true, "allGeneSymbolsVerified": true } ], "limitations": [ "Independent implementation of the same descriptive calculation on the same named public cohorts; not a new independent study.", "Original raw-input hashes were not retained. Current official input identity is pinned here, but byte-identical inputs across the historical and reproduction runs cannot be demonstrated.", "Counts use tumour samples, not a deduplicated patient denominator; they do not estimate clinical HER2 positivity, drug response, causality or cure.", "Exact agreement of output fields is computational reproduction only; no independent biological or external laboratory validation was performed.", "Title, retrieval date and prose method metadata are outside numerical comparison; all fields under original results are compared exactly, including reported percentages." ], "rerunCommand": "python3 scripts/reproduce-a1.py --output-dir data/reproductions/2026-09-30/A1", "report": { "path": "data/reproductions/2026-09-30/A1/result.json", "sha256": "668592ea447c9fde21d692729659962602afccae89621d0033044068a4fd6858" } }, { "schemaVersion": 1, "id": "A3-2026-09-30", "analysisId": "A3", "kind": "computational-reproduction", "scope": "same-cohort-independent-implementation", "scopeDetail": "Same named UniProt isoform pair and biological record; no patient cohort is involved.", "independentBiologicalValidation": false, "by": "Codex (GPT-6), A3 reproduction agent", "added": "2026-09-30", "date": "2026-09-30", "rerunCommand": "python3 scripts/reproduce-a3.py", "fetchedAtUtc": "2026-09-29T18:58:06Z", "original": { "path": "data/analyses/A3-cldn18-isoforms.json", "sha256": "7a7899b3b53da728777f624a57c9c308a71444f53df8d47bb3314f3ad036c14d" }, "inputs": { "path": "data/reproductions/2026-09-30/A3/manifest.json", "sha256": "20fc097e53743af76529caed9b5674ce736c1db3ba91ccc9b70d0de7883d41d4" }, "implementation": { "script": "scripts/reproduce-a3.py", "sha256": "1734d3e642bb257a9b09ecc27b1c2873783f0cef85287adfbccb482bfdcb2cea", "author": "Codex (GPT-6), A3 reproduction agent", "language": "Python", "independentOfOriginalCode": true }, "originalRawInputIdentity": { "status": "unverified", "reason": "No original raw FASTA/entry snapshots accompany the original A3 artifact in data/analyses or data/sources. Byte identity with the original 2026-09-28 inputs is unverified; agreement is with the saved scientific results using a freshly frozen official snapshot." }, "referenceArtifactUnchanged": true, "limitations": [ "New Python implementation on the same named UniProt isoform pair; computational reproduction only.", "No original raw FASTA/entry snapshots accompany the original A3 artifact in data/analyses or data/sources. Byte identity with the original 2026-09-28 inputs is unverified; agreement is with the saved scientific results using a freshly frozen official snapshot.", "Canonical topology is an annotation, not independently measured here. This calculation does not establish that canonical topology holds for isoform A2.", "No sequence alignment is inferred: equal-length sequences are compared at identical 1-based positions. Unequal lengths are treated as incomparable for this method.", "Alternative-sequence annotation drift or topology drift makes the whole analysis incomparable to the original annotation snapshot; individual sequence checks remain reported.", "No independent biological cohort, experiment, binding, therapeutic efficacy, safety, or clinical benefit is evaluated." ], "computed": { "lengths": { "P56856-1": 261, "P56856-2": 261 }, "differingPositions": 21, "span": { "first": 2, "last": 69 }, "identicalFrom": 70, "differences": [ { "pos": 2, "a1": "S", "a2": "A" }, { "pos": 3, "a1": "T", "a2": "V" }, { "pos": 5, "a1": "T", "a2": "A" }, { "pos": 8, "a1": "V", "a2": "G" }, { "pos": 9, "a1": "V", "a2": "L" }, { "pos": 10, "a1": "A", "a2": "G" }, { "pos": 12, "a1": "L", "a2": "V" }, { "pos": 13, "a1": "L", "a2": "V" }, { "pos": 15, "a1": "I", "a2": "L" }, { "pos": 16, "a1": "L", "a2": "I" }, { "pos": 18, "a1": "L", "a2": "I" }, { "pos": 21, "a1": "C", "a2": "I" }, { "pos": 26, "a1": "G", "a2": "C" }, { "pos": 29, "a1": "M", "a2": "Q" }, { "pos": 37, "a1": "D", "a2": "N" }, { "pos": 42, "a1": "S", "a2": "A" }, { "pos": 45, "a1": "Q", "a2": "N" }, { "pos": 47, "a1": "E", "a2": "Q" }, { "pos": 56, "a1": "Q", "a2": "E" }, { "pos": 65, "a1": "P", "a2": "G" }, { "pos": 69, "a1": "I", "a2": "L" } ], "topology": [ { "type": "Topological domain", "start": 1, "end": 6, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 7, "end": 27, "description": "Helical" }, { "type": "Topological domain", "start": 28, "end": 80, "description": "Extracellular" }, { "type": "Transmembrane", "start": 81, "end": 101, "description": "Helical" }, { "type": "Topological domain", "start": 102, "end": 122, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 123, "end": 143, "description": "Helical" }, { "type": "Topological domain", "start": 144, "end": 174, "description": "Extracellular" }, { "type": "Transmembrane", "start": 175, "end": 195, "description": "Helical" }, { "type": "Topological domain", "start": 196, "end": 261, "description": "Cytoplasmic" } ], "alternativeSequence": [ { "start": 1, "end": 69, "description": "in isoform A2" } ], "regionsTouched": [ "Topological domain 1-6 (Cytoplasmic)", "Transmembrane 7-27 (Helical)", "Topological domain 28-80 (Extracellular)" ] }, "comparison": { "passed": true, "checkedFields": [ "lengths", "differingPositions", "span", "identicalFrom", "differences", "topology", "alternativeSequence", "regionsTouched" ], "failedFields": [], "checkCount": 148, "checks": [ { "expectedPath": "/alternativeSequence", "actualPath": "/alternativeSequence", "expected": [ { "start": 1, "end": 69, "description": "in isoform A2" } ], "actual": [ { "start": 1, "end": 69, "description": "in isoform A2" } ], "pass": true }, { "expectedPath": "/alternativeSequence/0", "actualPath": "/alternativeSequence/0", "expected": { "start": 1, "end": 69, "description": "in isoform A2" }, "actual": { "start": 1, "end": 69, "description": "in 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"expectedPath": "/differences/5", "actualPath": "/differences/5", "expected": { "pos": 10, "a1": "A", "a2": "G" }, "actual": { "pos": 10, "a1": "A", "a2": "G" }, "pass": true }, { "expectedPath": "/differences/5/a1", "actualPath": "/differences/5/a1", "expected": "A", "actual": "A", "pass": true }, { "expectedPath": "/differences/5/a2", "actualPath": "/differences/5/a2", "expected": "G", "actual": "G", "pass": true }, { "expectedPath": "/differences/5/pos", "actualPath": "/differences/5/pos", "expected": 10, "actual": 10, "pass": true }, { "expectedPath": "/differences/6", "actualPath": "/differences/6", "expected": { "pos": 12, "a1": "L", "a2": "V" }, "actual": { "pos": 12, "a1": "L", "a2": "V" }, "pass": true }, { "expectedPath": "/differences/6/a1", "actualPath": "/differences/6/a1", "expected": "L", "actual": "L", "pass": true }, { "expectedPath": "/differences/6/a2", "actualPath": "/differences/6/a2", "expected": "V", "actual": "V", "pass": true }, { "expectedPath": 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The two required matrices and both profile mapping tables were not received; therefore full-source hashes, CN units, default-profile/2D joins, complete-case eligibility and the A4 association cannot be evaluated. 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This report contains stable public URLs and repository-relative paths; signed download query strings have been removed.", "report": { "path": "data/analyses/inputs/A4/access-report.json", "sha256": "dc8cdac0238cbbf31026b9f164b66ff1311882fc2701c62b48b27d2649543759" } } ], "cohortValidations": [ { "id": "CV-A1-20260930", "parentAnalysisId": "A1", "status": "completed", "scope": "independent-patient-cohort-descriptive-evaluation", "conclusion": "supported", "countingKey": "A1|stad_oncosg_2018:SG+ICGC+HK|brca_metabric:2012", "by": "Codex (GPT-6)", "added": "2026-09-30", "executedAtUtc": "2026-09-29T20:18:43.800449+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "title": { "en": "ERBB2 co-amplification in independent gastric and breast cohorts", "ko": "별도 위암·유방암 코호트의 ERBB2 공동증폭" }, "question": { "en": "Among ERBB2-amplified patients, is amplification of EGFR, MET, FGFR2, KRAS or CCNE1 more frequent in the selected gastric than breast cohorts?", "ko": "ERBB2 증폭 환자에서 EGFR·MET·FGFR2·KRAS·CCNE1 중 하나 이상의 공동증폭이 선택한 유방암 코호트보다 위암 코호트에서 더 흔한가" }, "summary": { "en": "The prespecified directional comparison was supported in these selected independent patient cohorts. This is a retrospective observational evaluation by the internal team.", "ko": "선택한 독립 환자 코호트에서 사전에 정한 비교 방향이 지지됐습니다. 내부 연구팀이 공개 관측 자료를 후향적으로 분석한 결과입니다." }, "cohorts": [ { "role": "gastric", "studyId": "stad_oncosg_2018", "label": "OncoSG · SG/ICGC/HK", "patients": 108, "erbb2Amplified": 17, "coamplified": 11, "proportion": 0.6470588235294118, "ci95": [ 0.4130036348521868, 0.8269027960275626 ] }, { "role": "breast", "studyId": "brca_metabric", "label": "METABRIC · original 2012", "patients": 1980, "erbb2Amplified": 298, "coamplified": 42, "proportion": 0.14093959731543623, "ci95": [ 0.10598990042575775, 0.18502863348901327 ] } ], "primary": { "riskDifference": 0.5061192262139755, "ci95": [ 0.2679477030264912, 0.6893276751364966 ], "fisherP": 0.000006552166340383826 }, "secondary": { "perGeneByCohort": [ { "role": "gastric", "denominator": 17, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 5, "proportion": 0.29411764705882354 }, { "gene": "MET", "coamplifiedPatients": 1, "proportion": 0.058823529411764705 }, { "gene": "FGFR2", "coamplifiedPatients": 0, "proportion": 0 }, { "gene": "KRAS", "coamplifiedPatients": 2, "proportion": 0.11764705882352941 }, { "gene": "CCNE1", "coamplifiedPatients": 8, "proportion": 0.47058823529411764 } ], "inference": "descriptive_only_no_per_gene_tests" }, { "role": "breast", "denominator": 298, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 12, "proportion": 0.040268456375838924 }, { "gene": "MET", "coamplifiedPatients": 3, "proportion": 0.010067114093959731 }, { "gene": "FGFR2", "coamplifiedPatients": 6, "proportion": 0.020134228187919462 }, { "gene": "KRAS", "coamplifiedPatients": 7, "proportion": 0.02348993288590604 }, { "gene": "CCNE1", "coamplifiedPatients": 18, "proportion": 0.06040268456375839 } ], "inference": "descriptive_only_no_per_gene_tests" } ], "gastricSourceStrata": [ { "sourceCohort": "SG", "eligiblePatients": 31, "ERBB2AmplifiedPatients": 5, "distantLocusCoamplifiedPatients": 3, "proportion": 0.6, "inference": "descriptive_only_no_stratum_tests" }, { "sourceCohort": "ICGC", "eligiblePatients": 23, "ERBB2AmplifiedPatients": 4, "distantLocusCoamplifiedPatients": 3, "proportion": 0.75, "inference": "descriptive_only_no_stratum_tests" }, { "sourceCohort": "HK", "eligiblePatients": 54, "ERBB2AmplifiedPatients": 8, "distantLocusCoamplifiedPatients": 5, "proportion": 0.625, "inference": "descriptive_only_no_stratum_tests" } ] }, "flow": [ { "role": "gastric", "studyId": "stad_oncosg_2018", "portalSamples": 147, "cnaListSamples": 108, "eligibilityListSamples": 108, "intersectedSamples": 108, "patientsSelectedBeforeOutcomes": 108, "completePatients": 108, "missingCallPatients": 0, "sourceCohorts": { "ICGC": 23, "HK": 54, "SG": 31 }, "samplePatientOneToOne": true }, { "role": "breast", "studyId": "brca_metabric", "portalSamples": 2509, "cnaListSamples": 2173, "eligibilityListSamples": 1980, "intersectedSamples": 1980, "patientsSelectedBeforeOutcomes": 1980, "completePatients": 1980, "missingCallPatients": 0, "sourceCohorts": { "1": 521, "2": 288, "3": 763, "4": 238, "5": 170 }, "samplePatientOneToOne": true } ], "plan": { "path": "docs/CV-A1-PLAN-2026-09-30.json", "sha256": "bd8192e7531de4446c04218121b4e4ceb15873429e5e282d686abee0cf5a625a" }, "inputs": { "path": "data/cohort-validations/2026-09-30/CV-A1/inputs/manifest.json", "sha256": "0178cf6169db653796c768ac584fa55c5777b84a90415a71cf7474fdd9b6a8b3" }, "rawResult": { "path": "data/cohort-validations/2026-09-30/CV-A1/stats-result.json", "sha256": "ade77f9e6bb0ae8c33ba627261426b678fb5856953cc42c3cc2c07ddc2b2d9aa" }, "implementation": { "path": "scripts/run-cohort-validation.py", "sha256": "d91f21e3a7f42d7c6710142008e3e68a7e907d17025f46069b0c477dde824e4e" }, "independence": { "path": "data/cohort-validations/2026-09-30/CV-A1/provenance/provenance.json", "sha256": "bbfa5c05fddf7550d6e824d1c1f1fe19f6c6a4f3d07b3d2d2184fad9c5d413f4" }, "limitations": [ { "en": "Independent patient collections are supported by source provenance and identifier checks; global donor deduplication across anonymous datasets was not possible.", "ko": "출처와 식별자 대조로 별도 환자군임을 확인했지만, 서로 다르게 익명화된 자료 사이의 동일인을 완전히 배제하지는 못했습니다." }, { "en": "Only SG, ICGC and HK gastric samples were used. The full gastric publication also included TCGA; those discovery patients were excluded.", "ko": "위암 자료는 SG·ICGC·HK 출처만 사용했습니다. 해당 논문 전체에는 TCGA도 포함되므로 그 환자군은 검증 대상에서 제외했습니다." }, { "en": "Gastric WGS/GISTIC and breast SNP6/DNAcopy differ. The same discrete amplification label does not guarantee identical thresholds; cancer type and assay are confounded.", "ko": "위암의 WGS/GISTIC과 유방암의 SNP6/DNAcopy는 측정 방식이 다릅니다. 같은 증폭 표지가 같은 절대 기준을 보장하지 않아 암종 효과와 측정법 효과를 분리할 수 없습니다." }, { "en": "Upstream gastric GISTIC threshold fitting may include the original publication collection; independent preprocessing was not established.", "ko": "위암 GISTIC 기준 산출에 원논문의 다른 표본이 포함됐을 가능성이 남아 있습니다. 전처리 과정 전체의 독립성은 확인하지 못했습니다." }, { "en": "The gastric ERBB2-amplified subgroup is small; its proportion interval is wide. The minimum subgroup count was a prespecified guard, not proof of adequate power.", "ko": "위암의 ERBB2 증폭 하위집단은 작고 비율의 신뢰구간이 넓습니다. 사전에 정한 최소 표본 기준을 넘은 것이 충분한 검정력을 뜻하지는 않습니다." }, { "en": "Gastric specimens are labelled Tumor, without verified primary status for every patient. Recruitment, geography, stage, prior therapy and purity are not matched.", "ko": "위암 검체는 종양으로 표기돼 있으나 모두 원발암인지 개별 확인되지는 않았습니다. 모집 방식·지역·병기·이전 치료·종양 순도는 맞추지 않았습니다." }, { "en": "The plan was locally locked before molecular retrieval, after the original result and publications were known; this was not an externally registered prospective study.", "ko": "기존 결과와 논문을 알고 있는 상태에서 분자 자료 수신 전에 계획을 고정했습니다. 외부에 사전 등록한 전향적 연구는 아닙니다." }, { "en": "Genomic co-amplification does not establish clinical HER2 positivity, a resistance mechanism, predictive accuracy or treatment benefit. No new biological experiment was performed.", "ko": "유전체 공동증폭만으로 임상 HER2 양성·내성 기전·예측 정확도·치료 이득을 입증하지 않습니다. 새 생물학적 실험은 수행하지 않았습니다." } ], "sources": [ { "label": "Guo et al. · gastric source collections", "url": "https://www.nature.com/articles/s41467-018-03828-2" }, { "label": "Curtis et al. · original METABRIC", "url": "https://www.nature.com/articles/nature10983" }, { "label": "cBioPortal · OncoSG metadata", "url": "https://www.cbioportal.org/api/studies/stad_oncosg_2018" }, { "label": "cBioPortal · METABRIC metadata", "url": "https://www.cbioportal.org/api/studies/brca_metabric" } ], "report": { "path": "data/cohort-validations/2026-09-30/CV-A1/result.json", "sha256": "cf12f1e8eb5794f77e95b4490df70d88f9ef976c19ec1c1426c138ccdc597d53" } }, { "id": "CV-A2-20260930", "parentAnalysisId": "A2", "status": "completed", "scope": "external-patient-cohort-descriptive-evaluation", "conclusion": "inconclusive", "countingKey": "A2|MBCPROJECT-2022:unique-primary-vs-distant-metastatic", "by": "Codex (GPT-6)", "added": "2026-09-30", "executedAtUtc": "2026-09-30T00:32:27.875621+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ESR1 detection in the external MBCproject cohort", "ko": "외부 MBCproject 코호트의 ESR1 검출 비교" }, "question": { "en": "Is reported ESR1 mutation detection more frequent in distant metastatic specimens than in pre-metastatic breast specimens, with one specimen per patient?", "ko": "환자별 검체 하나를 선택했을 때 ESR1 변이 검출이 전이 확인 전 유방 조직보다 원격전이 조직에서 더 흔한가" }, "summary": { "en": "The observed direction was higher in distant metastatic tissue, but the prespecified confidence-interval and exact-test criteria were not met. The result is inconclusive, with few detected events.", "ko": "원격전이 조직의 관찰 비율이 더 높았지만 사전에 정한 신뢰구간·정확검정 기준을 충족하지 못했습니다. 검출 사건이 적어 판단 불가로 기록합니다." }, "plan": { "path": "docs/CV-A2-PLAN-2026-09-30.json", "sha256": "e756a161ac5e002fbf97dbc9d12d4e3484a8935d638c3200c839d3178d43d6a3" }, "inputs": { "path": "data/cohort-validations/2026-09-30/CV-A2/outcomes/manifest.json", "sha256": "33ca5b03fd25afd041fe5186aa2feadbb4af48effa5e3664c0d76f19ede18464" }, "implementation": { "path": "scripts/run-cohort-a2.py", "sha256": "334d5b713158f3f9a3cff8fe08025dcd209276524f56f2325314f6701b722196" }, "rawResult": { "path": "data/cohort-validations/2026-09-30/CV-A2/run/stats-result.json", "sha256": "ae46aeaee47a4a348f70fcd99dd04fdd4ee086336fb4f50206c92aa404968d5d" }, "independence": { "path": "data/cohort-validations/2026-09-30/CV-A2/independence.json", "sha256": "13889ed1742a65f9ab4b9d4f21ad93324cbc20eb02ab2460829832cb9d83945e" }, "limitations": [ { "en": "The comparator is inferred from breast location and absence of metastatic disease at the specimen time. It is not confirmed to be the initial primary tumour and may include local recurrence; this is a directional evaluation with a proxy phenotype, not exact A2 replication.", "ko": "비교군은 유방 위치와 검체 시점의 전이 미확인 상태로 추정했습니다. 최초 원발암으로 확인되지 않았고 국소 재발이 포함될 수 있습니다. 대리 분류에 따른 방향 평가이며 A2의 정확한 재현은 아닙니다." }, { "en": "All participants entered a metastatic-breast-cancer project. Archived pre-metastatic samples are not an unselected nonmetastatic patient cohort.", "ko": "모든 참여자는 전이성 유방암 연구 사업에 등록됐습니다. 과거 전이 전 검체를 일반 비전이 환자 모집단으로 해석하지 않습니다." }, { "en": "A separately recruited and assayed project is documented, with no visible identifier overlap with MSK/TCGA. Anonymous donor overlap across projects remains unresolved.", "ko": "별도로 모집·측정한 연구 사업이며 공개 식별자는 MSK·TCGA와 겹치지 않았습니다. 연구 간 익명 환자의 실제 중복은 완전히 확인하지 못했습니다." }, { "en": "WXS assignment confirms profiling scope, not per-base ESR1 callability. No reported qualifying variant is non-detection, not proven biological absence. WES and the original MSK panel have different sensitivity.", "ko": "WXS 표시는 분석 범위를 확인할 뿐 ESR1의 모든 염기에서 충분한 측정을 보장하지 않습니다. 허용 변이 행의 부재는 비검출이며 생물학적 부재가 아닙니다. 원래 MSK 패널과 검출 민감도가 다릅니다." }, { "en": "Small event counts, specimen type, receptor subtype, timing and treatment exposure limit precision and comparability. HR+/HER2− subsets are descriptive only; missing values are not imputed.", "ko": "검출 사건이 적고 검체 유형·아형·시점·치료 노출이 달라 정밀도와 비교 가능성이 제한됩니다. HR+/HER2− 하위군은 기술 집계만 하며 결측을 추정해 채우지 않습니다." }, { "en": "Original A2 and related literature were known before this local protocol lock. No prospective blinding, new experiment, treatment effect or clinical prediction is claimed.", "ko": "내부 계획 고정 전에 기존 A2와 관련 문헌을 알고 있었습니다. 전향적 맹검·새 실험·치료 효과·임상 예측을 입증한 것으로 주장하지 않습니다." } ], "sources": [ { "label": "MBCproject public study and source version", "url": "https://github.com/cBioPortal/datahub/tree/86690e1ed9752b1dcd50b5657f5f05eafa4b6b78/public/brca_mbcproject_2022" }, { "label": "MBCproject cohort description · 2023 preprint", "url": "https://www.medrxiv.org/content/10.1101/2023.06.07.23291117v1" }, { "label": "Source data license · ODbL", "url": "https://github.com/cBioPortal/datahub/blob/86690e1ed9752b1dcd50b5657f5f05eafa4b6b78/public/brca_mbcproject_2022/LICENSE" } ], "reuse": { "license": "ODbL-1.0", "source": "cBioPortal DataHub / The Metastatic Breast Cancer Project", "notice": "Aggregate derived research data; source attribution retained. Shared adapted data are offered under the source ODbL terms." }, "cohorts": [ { "role": "primary", "studyId": "brca_mbcproject_2022", "label": { "en": "Pre-metastatic breast tissue", "ko": "전이 확인 전 유방 조직" }, "patients": 84, "mutated": 1, "proportion": 0.011904761904761904, "ci95": [ 0.002104583087549218, 0.06439543750771401 ] }, { "role": "metastatic", "studyId": "brca_mbcproject_2022", "label": { "en": "Distant metastatic tissue", "ko": "원격 전이 조직" }, "patients": 33, "mutated": 3, "proportion": 0.09090909090909091, "ci95": [ 0.03140394152458163, 0.23572605646469735 ] } ], "primary": { "endpoint": "reported_nonsynonymous_ESR1_variant", "contrast": "metastatic_minus_primary", "riskDifference": 0.07900432900432901, "newcombeWilson95CI": [ -0.0003438519989373279, 0.2241525188572619 ], "twoSidedFisherExactP": 0.06733799092356653, "numberOfPrimaryTests": 1, "contingencyTable": [ [ 3, 30 ], [ 1, 83 ] ], "tableRows": [ "metastatic", "primary" ], "tableColumns": [ "reported_variant", "no_reported_accepted_variant" ], "testStatus": "calculated" }, "secondary": { "hrPositiveHer2Negative": { "inference": "descriptive_only_no_secondary_tests", "cohorts": [ { "role": "primary", "studyId": "brca_mbcproject_2022", "label": { "en": "Pre-metastatic breast tissue", "ko": "전이 확인 전 유방 조직" }, "patients": 19, "mutated": 0, "proportion": 0, "ci95": [ 1.3877787807814457e-17, 0.16817922405261632 ] }, { "role": "metastatic", "studyId": "brca_mbcproject_2022", "label": { "en": "Distant metastatic tissue", "ko": "원격 전이 조직" }, "patients": 11, "mutated": 2, "proportion": 0.18181818181818182, "ci95": [ 0.051367689746085105, 0.47698056196084426 ] } ] } }, "flow": { "portalSamples": 379, "sequencedSamples": 379, "candidatePrimaryPatients": 89, "candidateMetastaticPatients": 33, "overlappingPatientsAssignedMetastatic": 5, "selectedPrimaryPatients": 84, "selectedMetastaticPatients": 33, "uniqueSelectedPatients": 117, "excludedSamples": { "notEligibleTissueOrSetting": 243, "notSequencedOrWxs": 0, "missingNumericTime": 0 }, "sampleSelectionUsesOutcomes": false }, "report": { "path": "data/cohort-validations/2026-09-30/CV-A2/result.json", "sha256": "31887fd5049d84914211516776692d0cda8eea808d82170974c6c98b044b12db" } }, { "id": "CV-A3", "parentAnalysisId": "A1", "status": "completed", "scope": "independent-patient-cohort-descriptive-evaluation", "countingKey": "A1|egc_msk_2023:anatomical_gastric248|brca_metabric:2012:reused", "title": { "en": "EGC-MSK gastric reported-CNA contrast with a reused METABRIC comparator", "ko": "새 위암 자료와 재사용 유방암 비교군의 증폭 관찰" }, "question": { "en": "Among ERBB2-amplified complete cases, are reported amplifications at any of five distant loci more frequent in anatomically concordant EGC-MSK gastric cases than in the frozen original METABRIC breast comparator?", "ko": "여섯 유전자의 측정값이 모두 있는 ERBB2 증폭 환자에서, 다른 다섯 유전자 중 하나 이상의 증폭이 새 EGC-MSK 위암 자료에서 고정된 기존 METABRIC 유방암 비교군보다 더 흔한가?" }, "summary": { "en": "The prespecified primary contrast is inconclusive: 3/26 gastric versus 42/298 reused breast amplified complete cases. The risk difference is -2.56 percentage points, with a 95% interval spanning -11.29 to +15.23 points; the two-sided Fisher p value is approximately 1. A negative point estimate alone is not evidence of an opposite direction.", "ko": "사전 고정한 주분석은 판단 불가다. 여섯 유전자가 완전 관측된 ERBB2 증폭 환자 중 공동증폭은 새 위암군 26명 중 3명, 재사용 유방암군 298명 중 42명이었다. 비율 차이는 -2.56퍼센트포인트이며 95% 구간은 -11.29~+15.23퍼센트포인트, 양측 피셔 검정 p값은 약 1이다. 음의 점추정치만으로 반대 방향을 입증한 것은 아니다." }, "by": "Codex (GPT-6)", "added": "2026-09-30", "executedAtUtc": "2026-09-30T06:02:24.849947+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "plan": { "path": "docs/campaigns/2026-09-30-24h/cohort-final-plan/analysis-plan.locked.json", "sha256": "85ab16ed3861a59e6d1fed8f1f37520c5f43b4ecb741c55331413f080c9cbfaf" }, "inputs": { "path": "data/cohort-validations/2026-09-30/CV-A3/inputs/attempt01/manifest.json", "sha256": "c41662f54ea7a7c8047f63350df5231c07d899fe749ca2acefd7edc453185f1e" }, "rawResult": { "path": "data/cohort-validations/2026-09-30/CV-A3/run01/result.json", "sha256": "77610d90f697b582e83e44214c6b271d2a1652d0b8060f6545472d885ca088c2" }, "implementation": { "path": "docs/campaigns/2026-09-30-24h/cohort-code-review/run-egc-cohort.py", "sha256": "3b4f341181e46225ce7779c3e8e856cb29726219ac659d8d1629315852b3629a" }, "acquisitionImplementation": { "path": "docs/campaigns/2026-09-30-24h/cohort-acquisition-draft/acquire-egc-cna.py", "sha256": "aa0bef04cc448c6477aa47c6f4d55908865873bc36ca75a6f48b2f374f959ac3" }, "independence": { "path": "docs/campaigns/2026-09-30-24h/cohort-preflight/independence-audit.json", "sha256": "ea7a9c2cc27449b373d99690525b49e06605a99531bbcad86a70cbc114c0a6cb" }, "independentReview": { "path": "docs/campaigns/2026-09-30-24h/cohort-raw-independent/comparison-review.json", "sha256": "6289a5da02e8c29eacc44b20aa560cc2cd35aab9d3997d3968e74af82a73c75f" }, "independentResult": { "path": "docs/campaigns/2026-09-30-24h/cohort-raw-independent/independent-result.json", "sha256": "248c7b65de3ab63ec7b5db566f244afffe673608d61fe32f7ea19b53028137e9" }, "independentImplementation": { "path": "docs/campaigns/2026-09-30-24h/cohort-raw-independent/reconstruct.py", "sha256": "d9270ab791212a1b833c5bf2d83645eef07c4bc397d342b69720631dc55ff19b" }, "cohorts": [ { "role": "gastric", "studyId": "egc_msk_2023", "label": "EGC-MSK 2023 · anatomically concordant gastric", "patients": 248, "erbb2Amplified": 26, "coamplified": 3, "proportion": 0.11538461538461539, "ci95": [ 0.04003244623610615, 0.2897590321171364 ], "reusedComparator": false }, { "role": "breast", "studyId": "brca_metabric", "label": "METABRIC 2012 · reused frozen comparator", "patients": 1980, "erbb2Amplified": 298, "coamplified": 42, "proportion": 0.14093959731543623, "ci95": [ 0.10598990042575776, 0.18502863348901324 ], "reusedComparator": true } ], "flow": [ { "role": "gastric", "studyId": "egc_msk_2023", "patientsSelectedBeforeOutcomes": 248, "completePatients": 248, "missingCallPatients": 0, "samplePatientOneToOne": true, "reusedComparator": false }, { "role": "breast", "studyId": "brca_metabric", "patientsSelectedBeforeOutcomes": 1980, "completePatients": 1980, "missingCallPatients": 0, "samplePatientOneToOne": true, "reusedComparator": true } ], "primary": { "riskDifference": -0.02555498193082084, "ci95": [ -0.11285785992519473, 0.15228741606101714 ], "fisherP": 0.9999999999997333, "numberOfPrimaryTests": 1, "minimumAmplifiedCountMet": true, "estimable": true }, "secondary": { "cohortSummaries": { "gastric": { "candidatePatients": 248, "completeCasePatients": 248, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 26, "distantLocusCoamplifiedPatients": 3, "proportion": 0.11538461538461539, "wilson95CI": [ 0.04003244623610615, 0.2897590321171364 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 26 }, "MET": { "patients": 1, "denominator": 26 }, "FGFR2": { "patients": 0, "denominator": 26 }, "KRAS": { "patients": 0, "denominator": 26 }, "CCNE1": { "patients": 2, "denominator": 26 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 26, "definitePositive": 3, "definiteNegative": 23, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.11538461538461539, 0.11538461538461539 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "breastReusedComparator": { "candidatePatients": 1980, "completeCasePatients": 1980, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 298, "distantLocusCoamplifiedPatients": 42, "proportion": 0.14093959731543623, "wilson95CI": [ 0.10598990042575776, 0.18502863348901324 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 12, "denominator": 298 }, "MET": { "patients": 3, "denominator": 298 }, "FGFR2": { "patients": 6, "denominator": 298 }, "KRAS": { "patients": 7, "denominator": 298 }, "CCNE1": { "patients": 18, "denominator": 298 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 298, "definitePositive": 42, "definiteNegative": 256, "unresolved": 0, "eventCountBounds": [ 42, 42 ], "proportionBounds": [ 0.14093959731543623, 0.14093959731543623 ], "inference": "descriptive_missing_target_extremes_no_test" } } }, "sensitivity": { "original_portal_label_280": { "gastric": { "candidatePatients": 280, "completeCasePatients": 280, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 28, "distantLocusCoamplifiedPatients": 4, "proportion": 0.14285714285714285, "wilson95CI": [ 0.05699005319749392, 0.31489802163525293 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 1, "denominator": 28 }, "MET": { "patients": 1, "denominator": 28 }, "FGFR2": { "patients": 0, "denominator": 28 }, "KRAS": { "patients": 0, "denominator": 28 }, "CCNE1": { "patients": 2, "denominator": 28 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 28, "definitePositive": 4, "definiteNegative": 24, "unresolved": 0, "eventCountBounds": [ 4, 4 ], "proportionBounds": [ 0.14285714285714285, 0.14285714285714285 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "contrast": { "riskDifference": 0.0019175455417066167, "newcombeWilson95CI": [ -0.09460706374179773, 0.1774725092522915 ], "estimable": true, "inference": "descriptive_only_no_test_or_direction_label" } }, "primary_specimens": { "gastric": { "candidatePatients": 177, "completeCasePatients": 177, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 21, "distantLocusCoamplifiedPatients": 3, "proportion": 0.14285714285714285, "wilson95CI": [ 0.04981012499725268, 0.34636060280620945 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 21 }, "MET": { "patients": 1, "denominator": 21 }, "FGFR2": { "patients": 0, "denominator": 21 }, "KRAS": { "patients": 0, "denominator": 21 }, "CCNE1": { "patients": 2, "denominator": 21 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 21, "definitePositive": 3, "definiteNegative": 18, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.14285714285714285, 0.14285714285714285 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "contrast": { "riskDifference": 0.0019175455417066167, "newcombeWilson95CI": [ -0.10104648042529656, 0.2084003281748399 ], "estimable": true, "inference": "descriptive_only_no_test_or_direction_label" } }, "adeno_or_signet_histology": { "gastric": { "candidatePatients": 238, "completeCasePatients": 238, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 25, "distantLocusCoamplifiedPatients": 3, "proportion": 0.12, "wilson95CI": [ 0.04166817150440358, 0.2995579392092732 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 25 }, "MET": { "patients": 1, "denominator": 25 }, "FGFR2": { "patients": 0, "denominator": 25 }, "KRAS": { "patients": 0, "denominator": 25 }, "CCNE1": { "patients": 2, "denominator": 25 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 25, "definitePositive": 3, "definiteNegative": 22, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.12, 0.12 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "contrast": { "riskDifference": -0.020939597315436237, "newcombeWilson95CI": [ -0.11082685150744341, 0.16198807922849587 ], "estimable": true, "inference": "descriptive_only_no_test_or_direction_label" } }, "matched_normal": { "gastric": { "candidatePatients": 246, "completeCasePatients": 246, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 26, "distantLocusCoamplifiedPatients": 3, "proportion": 0.11538461538461539, "wilson95CI": [ 0.04003244623610615, 0.2897590321171364 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 26 }, "MET": { "patients": 1, "denominator": 26 }, "FGFR2": { "patients": 0, "denominator": 26 }, "KRAS": { "patients": 0, "denominator": 26 }, "CCNE1": { "patients": 2, "denominator": 26 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 26, "definitePositive": 3, "definiteNegative": 23, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.11538461538461539, 0.11538461538461539 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "contrast": { "riskDifference": -0.02555498193082084, "newcombeWilson95CI": [ -0.11285785992519473, 0.15228741606101714 ], "estimable": true, "inference": "descriptive_only_no_test_or_direction_label" } } }, "descriptiveStrata": { "sampleType": { "Primary": { "candidatePatients": 177, "completeCasePatients": 177, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 21, "distantLocusCoamplifiedPatients": 3, "proportion": 0.14285714285714285, "wilson95CI": [ 0.04981012499725268, 0.34636060280620945 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 21 }, "MET": { "patients": 1, "denominator": 21 }, "FGFR2": { "patients": 0, "denominator": 21 }, "KRAS": { "patients": 0, "denominator": 21 }, "CCNE1": { "patients": 2, "denominator": 21 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 21, "definitePositive": 3, "definiteNegative": 18, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.14285714285714285, 0.14285714285714285 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "Metastasis": { "candidatePatients": 71, "completeCasePatients": 71, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 5, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 0, 0.43448246478317476 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 5 }, "MET": { "patients": 0, "denominator": 5 }, "FGFR2": { "patients": 0, "denominator": 5 }, "KRAS": { "patients": 0, "denominator": 5 }, "CCNE1": { "patients": 0, "denominator": 5 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 5, "definitePositive": 0, "definiteNegative": 5, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "Unknown": { "candidatePatients": 0, "completeCasePatients": 0, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } } }, "panel": { "IMPACT341": { "candidatePatients": 47, "completeCasePatients": 47, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 8, "distantLocusCoamplifiedPatients": 1, "proportion": 0.125, "wilson95CI": [ 0.02241749145005667, 0.4708881822128535 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 8 }, "MET": { "patients": 1, "denominator": 8 }, "FGFR2": { "patients": 0, "denominator": 8 }, "KRAS": { "patients": 0, "denominator": 8 }, "CCNE1": { "patients": 0, "denominator": 8 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 8, "definitePositive": 1, "definiteNegative": 7, "unresolved": 0, "eventCountBounds": [ 1, 1 ], "proportionBounds": [ 0.125, 0.125 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "IMPACT410": { "candidatePatients": 75, "completeCasePatients": 75, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 9, "distantLocusCoamplifiedPatients": 2, "proportion": 0.2222222222222222, "wilson95CI": [ 0.06322510711784671, 0.5474110308930111 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 9 }, "MET": { "patients": 0, "denominator": 9 }, "FGFR2": { "patients": 0, "denominator": 9 }, "KRAS": { "patients": 0, "denominator": 9 }, "CCNE1": { "patients": 2, "denominator": 9 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 9, "definitePositive": 2, "definiteNegative": 7, "unresolved": 0, "eventCountBounds": [ 2, 2 ], "proportionBounds": [ 0.2222222222222222, 0.2222222222222222 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "IMPACT468": { "candidatePatients": 122, "completeCasePatients": 122, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 9, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 0, 0.2991450484195441 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 9 }, "MET": { "patients": 0, "denominator": 9 }, "FGFR2": { "patients": 0, "denominator": 9 }, "KRAS": { "patients": 0, "denominator": 9 }, "CCNE1": { "patients": 0, "denominator": 9 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 9, "definitePositive": 0, "definiteNegative": 9, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "IMPACT505": { "candidatePatients": 4, "completeCasePatients": 4, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } }, "Unknown": { "candidatePatients": 0, "completeCasePatients": 0, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } } }, "ageGroup": { "<50": { "candidatePatients": 77, "completeCasePatients": 77, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 3, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 5.551115123125783e-17, 0.5614970317550454 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 3 }, "MET": { "patients": 0, "denominator": 3 }, "FGFR2": { "patients": 0, "denominator": 3 }, "KRAS": { "patients": 0, "denominator": 3 }, "CCNE1": { "patients": 0, "denominator": 3 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 3, "definitePositive": 0, "definiteNegative": 3, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, ">=50": { "candidatePatients": 171, "completeCasePatients": 171, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 23, "distantLocusCoamplifiedPatients": 3, "proportion": 0.13043478260869565, "wilson95CI": [ 0.04537659093631238, 0.32127482270095964 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 23 }, "MET": { "patients": 1, "denominator": 23 }, "FGFR2": { "patients": 0, "denominator": 23 }, "KRAS": { "patients": 0, "denominator": 23 }, "CCNE1": { "patients": 2, "denominator": 23 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 23, "definitePositive": 3, "definiteNegative": 20, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.13043478260869565, 0.13043478260869565 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "unknown": { "candidatePatients": 0, "completeCasePatients": 0, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } } }, "stageGroup": { "I-III": { "candidatePatients": 89, "completeCasePatients": 89, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 6, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 2.7755575615628914e-17, 0.3903342879021653 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 6 }, "MET": { "patients": 0, "denominator": 6 }, "FGFR2": { "patients": 0, "denominator": 6 }, "KRAS": { "patients": 0, "denominator": 6 }, "CCNE1": { "patients": 0, "denominator": 6 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 6, "definitePositive": 0, "definiteNegative": 6, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "IV": { "candidatePatients": 158, "completeCasePatients": 158, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 20, "distantLocusCoamplifiedPatients": 3, "proportion": 0.15, "wilson95CI": [ 0.052368745896216595, 0.36041886474075696 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 20 }, "MET": { "patients": 1, "denominator": 20 }, "FGFR2": { "patients": 0, "denominator": 20 }, "KRAS": { "patients": 0, "denominator": 20 }, "CCNE1": { "patients": 2, "denominator": 20 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 20, "definitePositive": 3, "definiteNegative": 17, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.15, 0.15 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "unknown": { "candidatePatients": 1, "completeCasePatients": 1, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } } }, "histology": { "Adenocarcinoma": { "candidatePatients": 163, "completeCasePatients": 163, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 23, "distantLocusCoamplifiedPatients": 3, "proportion": 0.13043478260869565, "wilson95CI": [ 0.04537659093631238, 0.32127482270095964 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 23 }, "MET": { "patients": 1, "denominator": 23 }, "FGFR2": { "patients": 0, "denominator": 23 }, "KRAS": { "patients": 0, "denominator": 23 }, "CCNE1": { "patients": 2, "denominator": 23 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 23, "definitePositive": 3, "definiteNegative": 20, "unresolved": 0, "eventCountBounds": [ 3, 3 ], "proportionBounds": [ 0.13043478260869565, 0.13043478260869565 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "Signet_Diffuse": { "candidatePatients": 75, "completeCasePatients": 75, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 2, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 0, 0.6576197724933469 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 2 }, "MET": { "patients": 0, "denominator": 2 }, "FGFR2": { "patients": 0, "denominator": 2 }, "KRAS": { "patients": 0, "denominator": 2 }, "CCNE1": { "patients": 0, "denominator": 2 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 2, "definitePositive": 0, "definiteNegative": 2, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "Other": { "candidatePatients": 10, "completeCasePatients": 10, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 1, "distantLocusCoamplifiedPatients": 0, "proportion": 0, "wilson95CI": [ 0, 0.7934506856227626 ], "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 1 }, "MET": { "patients": 0, "denominator": 1 }, "FGFR2": { "patients": 0, "denominator": 1 }, "KRAS": { "patients": 0, "denominator": 1 }, "CCNE1": { "patients": 0, "denominator": 1 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 1, "definitePositive": 0, "definiteNegative": 1, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": [ 0, 0 ], "inference": "descriptive_missing_target_extremes_no_test" } }, "Unknown": { "candidatePatients": 0, "completeCasePatients": 0, "excludedMissingPatients": 0, "ERBB2AmplifiedPatients": 0, "distantLocusCoamplifiedPatients": 0, "proportion": null, "wilson95CI": null, "ERBB2UnknownPatients": 0, "perGeneMissing": { "ERBB2": 0, "EGFR": 0, "MET": 0, "FGFR2": 0, "KRAS": 0, "CCNE1": 0 }, "missingCellStates": { "ERBB2": {}, "EGFR": {}, "MET": {}, "FGFR2": {}, "KRAS": {}, "CCNE1": {} }, "perGeneCoamplified": { "EGFR": { "patients": 0, "denominator": 0 }, "MET": { "patients": 0, "denominator": 0 }, "FGFR2": { "patients": 0, "denominator": 0 }, "KRAS": { "patients": 0, "denominator": 0 }, "CCNE1": { "patients": 0, "denominator": 0 } }, "partialTargetBound": { "ERBB2ObservedAmplified": 0, "definitePositive": 0, "definiteNegative": 0, "unresolved": 0, "eventCountBounds": [ 0, 0 ], "proportionBounds": null, "inference": "descriptive_missing_target_extremes_no_test" } } } } }, "conclusion": "inconclusive", "independenceSummary": { "newCollection": "egc_msk_2023", "reusedComparator": "brca_metabric", "reusedComparatorNewCoverage": 0, "globalDonorIdentity": "not_established", "independentOfPreviousSharedComparatorEvaluation": false }, "coverage": { "primaryCompleteCasePatients": 248, "sensitivityOnlyCandidates": 32, "reusedComparatorPatients": 1980, "reusedComparatorNewPatients": 0, "definition": "primary_complete_case_patients_only_study_union" }, "limitations": [ { "en": "The EGC-MSK gastric collection is new to this comparison; the same frozen 1,980-person METABRIC arm is reused from CV-A1 and contributes no new patient coverage. The two evaluations share a comparator and are correlated.", "ko": "새 위암 수집 자료를 평가했지만 유방암 1,980명은 기존 평가의 고정 비교군을 재사용했다. 새 환자 수에 더하지 않으며, 두 평가는 같은 비교군을 공유하므로 서로 독립적이지 않다." }, { "en": "Exact public identifiers do not overlap the frozen comparison sources; global donor identity across anonymized studies is not established.", "ko": "고정된 비교 자료와 공개 식별자의 일치는 없었지만 익명화된 연구 간 실제 동일인 여부를 완전히 확인한 것은 아니다." }, { "en": "Reported category-2 calls on a targeted panel are compared with array-derived discrete calls. Platform and cancer type remain confounded, with no verified common absolute amplification threshold or panel-wise caller calibration.", "ko": "표적 패널과 배열 기반 자료의 범주 2 판정을 비교했다. 플랫폼과 암종의 영향은 분리되지 않았으며 공통 절대 증폭 기준이나 패널별 판정 보정은 검증하지 않았다." }, { "en": "This reported-call endpoint does not measure clinical HER2 status, treatment benefit, causal resistance, drug sensitivity or predictive performance.", "ko": "이 관찰은 임상 허투 판정, 치료 이득, 인과적 내성 기전, 약제 감수성이나 환자 예측 성능을 평가한 것이 아니다." }, { "en": "The 248-person anatomical primary set was fixed before molecular retrieval from a frozen 280-person portal-label frame. The original 280 and three other prespecified sensitivity groups remain descriptive; none replaces the primary or receives an extra test or directional conclusion.", "ko": "분자 자료를 받기 전에 기존 진단명 기준 280명 중 해부학적으로 일치한 248명을 주분석으로 고정했다. 원래 280명과 다른 사전 민감도 집단 세 개는 기술적 집계이며 주분석을 대체하거나 추가 검정·방향 판정을 받지 않는다." }, { "en": "Only primary complete-case EGC patients add headline patient coverage. The 32 sensitivity-only candidates and the reused comparator add no new headline records.", "ko": "대표 환자 지표에는 위암 주분석의 완전 관측 환자만 더한다. 민감도 분석에만 속한 32명과 재사용 비교군은 새 대표 환자 수에 더하지 않는다." }, { "en": "The local plan and code were locked before selected EGC molecular retrieval, after prior results and metadata were known. An incidental whole-release aggregate had been seen and disclosed; this was neither fully blinded nor externally preregistered.", "ko": "선택된 위암 분자 자료를 받기 전 계획과 코드를 고정했지만 이전 결과와 메타데이터는 알고 있었다. 우발적으로 본 전체 자료 집계도 공개했으며 완전한 눈가림이나 외부 사전 등록으로 주장하지 않는다." }, { "en": "The minimum of ten amplified complete cases per arm is a guard, not a power calculation. Intervals remain broad, and a valid inconclusive result is not equivalence or proof of no biological difference.", "ko": "군별 증폭 완전 관측 환자 10명 기준은 최소 보호 조건이지 검정력 계산이 아니다. 구간이 넓으며 판단 불가는 동등성이나 생물학적 차이의 부재를 입증하지 않는다." }, { "en": "Missing calls are never filled with zero; incomplete selected cases are excluded without specimen replacement. Missingness, partial-target bounds, and all prespecified strata are reported, including empty strata.", "ko": "결측값을 0으로 채우지 않고 선택한 환자의 값이 불완전하면 검체를 대체하지 않은 채 제외한다. 결측, 부분 관측의 극단 범위, 비어 있는 집단을 포함한 모든 사전 하위집단 집계를 남긴다." }, { "en": "Independent software reconstructed the original frozen bytes before inspecting the root result and matched all aggregate results. This is internal raw-data verification, not a new biological experiment or laboratory replication.", "ko": "별도 코드가 주작업자 결과를 보기 전에 원자료를 재구성해 봉인했고 전체 집계가 일치했다. 내부 원자료 검증이며 새 생물학 실험이나 외부 실험실 재현은 아니다." } ], "sources": [ { "label": "Fixed cBioPortal DataHub EGC-MSK 2023 release", "url": "https://github.com/cBioPortal/datahub/tree/179cc699e4d305c397ee2bf3d13de7baf02d4c70/public/egc_msk_2023" }, { "label": "cBioPortal EGC-MSK 2023 study", "url": "https://www.cbioportal.org/study/summary?id=egc_msk_2023" }, { "label": "cBioPortal METABRIC study · reused frozen original cohort", "url": "https://www.cbioportal.org/study/summary?id=brca_metabric" } ], "report": { "path": "data/cohort-validations/2026-09-30/CV-A3/result.json", "sha256": "00376283beb8ed74341f02fb387fbcdc84ceba9e90aab5aeda4281ca4b8bea70" } }, { "id": "CV-A5-20261005", "parentAnalysisId": "A5", "status": "completed", "scope": "external-patient-cohort-paired-descriptive-evaluation", "conclusion": "inconclusive", "countingKey": "A5|AURORA-US-2023:paired-primary-vs-metastatic", "by": "Claude", "added": "2026-10-05", "executedAtUtc": "2026-10-05T13:41:25.768089+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "Paired ESR1 detection in the external AURORA US cohort", "ko": "외부 AURORA US 코호트의 짝지은 ESR1 검출" }, "question": { "en": "Within patients with both a primary and a metastatic whole-exome specimen, is a reported non-synonymous ESR1 variant detected more often in the metastatic specimen than in the primary specimen?", "ko": "원발암과 전이암의 전장 엑솜 검체가 모두 있는 환자에서, 보고된 비동의적 ESR1 변이가 원발암 검체보다 전이암 검체에서 더 자주 검출되는가" }, "summary": { "en": "Inconclusive. Among 36 paired patients a variant was reported in 2 metastatic and 1 primary specimens; only one pair was discordant, so the prespecified exact test cannot establish a direction. The point estimate alone is not evidence for or against the A5 pattern.", "ko": "판단 불가입니다. 짝지은 환자 36명 중 전이암 검체 2개와 원발암 검체 1개에 변이가 보고됐고, 불일치 쌍은 하나뿐이어서 사전에 정한 정확 검정으로 방향을 정할 수 없습니다. 점추정만으로 A5 양상을 지지하거나 반박하지 않습니다." }, "cohorts": [ { "role": "paired", "studyId": "brca_aurora_2023", "label": { "en": "AURORA US · paired primary and metastatic specimens", "ko": "AURORA US · 원발·전이 짝 검체" }, "patients": 36, "primaryDetected": 1, "metastasisDetected": 2 } ], "paired": { "pairs": 36, "cells": { "neither": 34, "primaryOnly": 0, "metastasisOnly": 1, "both": 1 }, "discordantPairs": 1, "metastasisDirectionShare": 1, "directionExact95CI": [ 0.024999999999999967, 1 ], "mcnemarExactP": 1, "primary": { "events": 1, "patients": 36, "proportion": 0.027777777777777776, "wilson95CI": [ 0.004920407139810443, 0.14169718653273855 ] }, "metastasis": { "events": 2, "patients": 36, "proportion": 0.05555555555555555, "wilson95CI": [ 0.015369986664161853, 0.18144657208647252 ] }, "pairedRiskDifference": 0.027777777777777776 }, "flow": { "portalSamples": 155, "sequencedSamples": 134, "excludedSamples": { "notSequencedOrWxs": 21, "otherSampleType": 0, "noSpecimenTimeline": 6, "missingNumericDay": 0, "discordantTypeOrPatient": 1 }, "patientsWithEligibleSpecimen": 46, "selectedPairs": 36, "selectedSamples": 72, "chronology": { "metastasisLater": 29, "sameDay": 3, "metastasisEarlier": 4 }, "sampleSelectionUsesOutcomes": false }, "limitations": [ { "en": "Whole-exome sequencing has limited depth for subclonal ESR1 variants; A5 used targeted MSK-IMPACT panels. A missing reported variant is non-detection, not proven absence, and detection rates are not comparable across the two assays.", "ko": "전장 엑솜 분석은 일부 세포에만 있는 ESR1 변이를 검출하는 깊이가 제한적입니다. A5는 표적 패널(MSK-IMPACT)을 썼습니다. 변이 미보고는 미검출일 뿐 생물학적 부재의 증명이 아니며, 두 분석법의 검출률을 그대로 비교할 수 없습니다." }, { "en": "Only one discordant pair was observed. The evaluation has little power; an inconclusive result does not show that the tissues are alike.", "ko": "불일치 쌍이 하나만 관찰됐습니다. 검정력이 낮으며, 판단 불가 결과가 두 조직이 같다는 뜻은 아닙니다." }, { "en": "The earliest dated specimen of each type was selected. The metastatic specimen was dated later in 29 pairs, the same day in 3 and earlier in 4; do not infer mutation acquisition or a treatment effect.", "ko": "유형별로 채취일이 가장 이른 검체를 골랐습니다. 전이암 검체가 더 늦은 쌍은 29개, 같은 날은 3개, 더 이른 쌍은 4개입니다. 변이 획득이나 치료 효과로 해석하지 않습니다." }, { "en": "Six sequenced specimens without a specimen-timeline day and one with discordant type labels were excluded by rule before outcomes. Receptor subtype and treatment history were not used; no subgroup analysis was prespecified.", "ko": "채취일 기록이 없는 분석 검체 6개와 유형 표기가 서로 다른 검체 1개는 결과를 보기 전에 정한 규칙으로 제외했습니다. 수용체 아형과 치료 이력은 쓰지 않았고 하위군 분석은 사전에 정하지 않았습니다." }, { "en": "AURORA US is a multi-institution network of patients with metastatic breast cancer. No selected identifier matches the MSK series used for A5, but anonymised records cannot prove that every donor differs.", "ko": "AURORA US는 전이성 유방암 환자를 모은 다기관 네트워크입니다. 선택한 식별자 중 A5에 쓴 MSK 자료와 일치하는 것은 없지만, 익명화된 기록으로 모든 환자가 다른 사람임을 입증할 수는 없습니다." } ], "sources": [ { "label": "cBioPortal study: Metastatic Breast Cancer (AURORA US Network, Nat Cancer 2023)", "url": "https://www.cbioportal.org/study/summary?id=brca_aurora_2023" }, { "label": "Garcia-Recio et al., Nat Cancer 2023 (PMID 36585450)", "url": "https://pubmed.ncbi.nlm.nih.gov/36585450/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/405d175a5189be972e6bd1a782a22248f16cfe37/public/brca_aurora_2023" } ], "plan": { "path": "docs/CV-A5-PLAN-2026-10-05.json", "sha256": "df8a65134dff52e63eea1f8863a263ba993d28a4edd9fdadfb8851f134f969fc" }, "inputs": { "path": "data/cohort-validations/2026-10-05/CV-A5/outcomes/manifest.json", "sha256": "e6f032f107e392f008a2428c20f5385e858331de5649cb4feaf9b3f217d82284" }, "rawResult": { "path": "data/cohort-validations/2026-10-05/CV-A5/run/stats-result.json", "sha256": "32d276accbb06f74c60b78df97134798c48d69b0027c0c3463e4ea7921386acc" }, "implementation": { "path": "scripts/run-cohort-a5.py", "sha256": "7248c747cdd3058bffd295bed25ad98108e00297105864f0f1a7b66bb181f926" }, "independence": { "path": "data/cohort-validations/2026-10-05/CV-A5/independence.json", "sha256": "9a2a6e54bc901a265117ac679d901b65fe82c30b54beb4c57471ededd4442d84" }, "report": { "path": "data/cohort-validations/2026-10-05/CV-A5/result.json", "sha256": "294b5843e3557015aabb0911f72db066a608a0a4cea84be3a3c8f92595409c1b" } }, { "id": "CV-A1-OM-20261006", "parentAnalysisId": "A1", "status": "completed", "scope": "external-patient-cohort-descriptive-evaluation", "conclusion": "supported", "countingKey": "A1|ORIGIMED-2020:primary-gastric-vs-primary-breast", "by": "Claude", "added": "2026-10-06", "executedAtUtc": "2026-10-06T11:05:21.759663+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 co-amplification in gastric and breast cancer on one sequencing panel", "ko": "같은 검사법으로 본 위암·유방암의 ERBB2 공동증폭" }, "question": { "en": "Among ERBB2-amplified patients sequenced on one targeted panel, is amplification of at least one of EGFR, MET, FGFR2, KRAS or CCNE1 more frequent in primary gastric adenocarcinoma than in primary invasive breast carcinoma?", "ko": "같은 표적 패널로 분석한 ERBB2 증폭 환자에서, EGFR·MET·FGFR2·KRAS·CCNE1 중 하나 이상의 공동증폭이 원발 침윤성 유방암보다 원발 위선암에서 더 흔한가" }, "summary": { "en": "The prespecified direction was supported. Co-amplification was reported in 25 of 65 ERBB2-amplified gastric patients and 6 of 53 ERBB2-amplified breast patients, measured by the same laboratory and panel. Most gastric events were CCNE1. This is a retrospective observational evaluation by the internal team, not a treatment finding.", "ko": "사전에 정한 비교 방향이 지지됐습니다. 같은 검사실의 같은 패널로 측정했을 때 공동증폭은 ERBB2 증폭 위암 환자 65명 중 25명, ERBB2 증폭 유방암 환자 53명 중 6명에서 보고됐습니다. 위암의 공동증폭은 대부분 CCNE1이었습니다. 내부 연구팀이 공개 관측 자료를 후향적으로 분석한 결과이며 치료 효과를 뜻하지 않습니다." }, "cohorts": [ { "role": "gastric", "studyId": "pan_origimed_2020", "label": { "en": "OrigiMed · primary gastric adenocarcinoma", "ko": "OrigiMed · 원발 위선암" }, "patients": 814, "erbb2Amplified": 65, "coamplified": 25, "proportion": 0.38461538461538464, "ci95": [ 0.275950073750021, 0.5061579719398692 ] }, { "role": "breast", "studyId": "pan_origimed_2020", "label": { "en": "OrigiMed · primary invasive breast carcinoma", "ko": "OrigiMed · 원발 침윤성 유방암" }, "patients": 223, "erbb2Amplified": 53, "coamplified": 6, "proportion": 0.11320754716981132, "ci95": [ 0.05293030947702562, 0.2257651911199219 ] } ], "primary": { "riskDifference": 0.2714078374455733, "ci95": [ 0.11495537502626207, 0.40707635228008654 ], "fisherP": 0.0013641073915802732 }, "secondary": { "perGeneByCohort": [ { "role": "gastric", "denominator": 65, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 1, "proportion": 0.015384615384615385 }, { "gene": "MET", "coamplifiedPatients": 1, "proportion": 0.015384615384615385 }, { "gene": "FGFR2", "coamplifiedPatients": 1, "proportion": 0.015384615384615385 }, { "gene": "KRAS", "coamplifiedPatients": 2, "proportion": 0.03076923076923077 }, { "gene": "CCNE1", "coamplifiedPatients": 20, "proportion": 0.3076923076923077 } ], "inference": "descriptive_only_no_per_gene_tests" }, { "role": "breast", "denominator": 53, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 3, "proportion": 0.05660377358490566 }, { "gene": "MET", "coamplifiedPatients": 0, "proportion": 0 }, { "gene": "FGFR2", "coamplifiedPatients": 1, "proportion": 0.018867924528301886 }, { "gene": "KRAS", "coamplifiedPatients": 2, "proportion": 0.03773584905660377 }, { "gene": "CCNE1", "coamplifiedPatients": 0, "proportion": 0 } ], "inference": "descriptive_only_no_per_gene_tests" } ] }, "flow": { "portalSamples": 10194, "copyNumberProfiledSamples": 10194, "cohorts": [ { "role": "gastric", "labelledSamples": 850, "excludedBeforeOutcomes": { "otherSpecimenType": 36, "notCopyNumberProfiled": 0, "laterSampleOfSamePatient": 0 }, "patientsSelectedBeforeOutcomes": 814, "completePatients": 814, "missingCallPatients": 0 }, { "role": "breast", "labelledSamples": 303, "excludedBeforeOutcomes": { "otherSpecimenType": 80, "notCopyNumberProfiled": 0, "laterSampleOfSamePatient": 0 }, "patientsSelectedBeforeOutcomes": 223, "completePatients": 223, "missingCallPatients": 0 } ], "sampleSelectionUsesOutcomes": false }, "limitations": [ { "en": "Patients were referred for clinical sequencing at one commercial laboratory in China. Stage, prior treatment and receptor subtype were not controlled, and the two groups were not matched.", "ko": "환자들은 중국의 한 민간 검사실에 임상 유전체 검사를 의뢰한 사람들입니다. 병기, 이전 치료, 수용체 아형을 통제하지 않았고 두 군을 짝짓지 않았습니다." }, { "en": "Copy number comes from a targeted panel called by the source laboratory. Category 2 is not a clinical HER2 immunohistochemistry or in situ hybridisation result, and its threshold was not set by this team.", "ko": "복제수는 원자료 검사실이 표적 패널에서 판정한 값입니다. 범주 2는 임상 HER2 면역조직화학·제자리부합법 결과가 아니며, 그 기준은 이 팀이 정하지 않았습니다." }, { "en": "One platform for both cancer types removes the assay difference of the first external evaluation, but not differences in tumour purity, sampling or case mix.", "ko": "두 암종을 같은 검사법으로 측정해 첫 외부 평가의 측정법 차이는 없앴지만, 종양 순도·검체 채취·환자 구성의 차이는 남아 있습니다." }, { "en": "Only primary specimens labelled gastric adenocarcinoma or invasive breast carcinoma were selected. Metastatic and recurrent specimens and other histologies were excluded by rule before outcomes.", "ko": "위선암 또는 침윤성 유방암으로 표기된 원발 검체만 골랐습니다. 전이·재발 검체와 다른 조직형은 결과를 보기 전에 정한 규칙으로 제외했습니다." }, { "en": "Gene-specific counts are descriptive and can overlap; no per-gene test was run. The breast group had 53 ERBB2-amplified patients, so its interval is wide.", "ko": "유전자별 집계는 기술적 수치이며 서로 겹칠 수 있습니다. 유전자별 검정은 하지 않았습니다. 유방암군의 ERBB2 증폭 환자는 53명이어서 구간이 넓습니다." }, { "en": "No selected identifier matches the earlier TCGA, OncoSG, METABRIC or EGC-MSK lists, but anonymised records cannot prove that every donor differs.", "ko": "선택한 식별자 중 앞선 TCGA·OncoSG·METABRIC·EGC-MSK 목록과 일치하는 것은 없지만, 익명화된 기록으로 모든 환자가 다른 사람임을 입증할 수는 없습니다." } ], "sources": [ { "label": "cBioPortal study: China Pan-cancer (OrigiMed, Nature 2022)", "url": "https://www.cbioportal.org/study/summary?id=pan_origimed_2020" }, { "label": "Wu et al., Nature 2022 (PMID 35871175)", "url": "https://pubmed.ncbi.nlm.nih.gov/35871175/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/dca75cb3f32b82d54a6f78bf0a6323e5b975aca1/public/pan_origimed_2020" } ], "plan": { "path": "docs/CV-A1-OM-PLAN-2026-10-06.json", "sha256": "c2d2fbe941ab132462caeb2a4ecbb3a776f0a9d6623bfabdef3d55579a6ecc47" }, "inputs": { "path": "data/cohort-validations/2026-10-06/CV-A1-OM/outcomes/manifest.json", "sha256": "e82a5231f43f05c649549efa03b65f2a36b34eeac2431d77916cc6de826b5d56" }, "rawResult": { "path": "data/cohort-validations/2026-10-06/CV-A1-OM/run/stats-result.json", "sha256": "a49320c74d39a82660ba8706e9f977326e280365d0f72dbf01dbeb0d6405dcce" }, "implementation": { "path": "scripts/run-cohort-a1-origimed.py", "sha256": "65529e0b6fcc78e0a6cdf253ce11a4683acb49539d4008171b32e27b693d2e48" }, "independence": { "path": "data/cohort-validations/2026-10-06/CV-A1-OM/independence.json", "sha256": "dad94b0cc9eeba1315fc53ba695d48c093b3bfb44d974aa30b46c7ce1e00974d" }, "report": { "path": "data/cohort-validations/2026-10-06/CV-A1-OM/result.json", "sha256": "170013191089c91e42549955759f9dbb5f0c71195e0ac09922df5747cc6bd371" } }, { "id": "CV-A2-MSK-20261007", "parentAnalysisId": "A2", "status": "completed", "scope": "same-institution-patient-disjoint-descriptive-evaluation", "externalCohort": false, "conclusion": "supported", "countingKey": "A2|MSK-BREAST-2025-2026:patient-disjoint-primary-vs-metastatic", "by": "Claude", "added": "2026-10-07", "executedAtUtc": "2026-10-06T17:29:37.793747+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "same_institution_patient_disjoint", "independenceNote": { "en": "Same institution and assay family as the original analysis. The patients are different people by MSK patient identifier, but this is not an external cohort; shared biases of the institution and pipeline would repeat.", "ko": "기존 분석과 같은 기관·같은 계열의 검사법입니다. MSK 환자번호 기준으로 환자는 겹치지 않지만 외부 코호트가 아니며, 기관과 분석 과정에서 생기는 치우침은 그대로 반복될 수 있습니다." }, "title": { "en": "ESR1 detection in MSK breast patients outside the earlier MSK series", "ko": "기존 자료에 없던 MSK 유방암 환자의 ESR1 검출 비교" }, "question": { "en": "Among MSK breast cancer patients who are not in any MSK series already analysed here, with one specimen per patient, is a reported non-synonymous ESR1 mutation more frequent in metastatic than in primary specimens?", "ko": "이미 분석한 MSK 자료에 들어 있지 않은 MSK 유방암 환자에서, 환자마다 검체 하나를 골랐을 때 비동의적 ESR1 변이가 원발 검체보다 전이 검체에서 더 흔한가" }, "summary": { "en": "The prespecified direction was supported. A reported ESR1 mutation was found in 278 of 2,352 patients with a metastatic specimen and 22 of 1,780 with a primary specimen. The direction was expected, and these patients come from the same institution as the original analysis, so this shows the pattern holds in different patients there rather than in an independent setting.", "ko": "사전에 정한 비교 방향이 지지됐습니다. ESR1 변이는 전이 검체 환자 2,352명 중 278명, 원발 검체 환자 1,780명 중 22명에서 보고됐습니다. 방향은 예상된 것이며, 환자들이 기존 분석과 같은 기관 소속이므로 독립된 환경이 아니라 같은 기관의 다른 환자에서도 같은 양상이 나타난다는 뜻입니다." }, "cohorts": [ { "role": "primary", "studyId": "breast_msk_2026 + breast_msk_2025", "label": { "en": "MSK breast, new patients · primary specimen", "ko": "MSK 유방암 신규 환자 · 원발 검체" }, "patients": 1780, "mutated": 22, "proportion": 0.012359550561797753, "ci95": [ 0.008176147400044347, 0.01864319721386677 ] }, { "role": "metastatic", "studyId": "breast_msk_2026 + breast_msk_2025", "label": { "en": "MSK breast, new patients · metastatic specimen", "ko": "MSK 유방암 신규 환자 · 전이 검체" }, "patients": 2352, "mutated": 278, "proportion": 0.11819727891156463, "ci95": [ 0.10576838778069488, 0.1318713127706928 ] } ], "primary": { "riskDifference": 0.10583772834976687, "newcombeWilson95CI": [ 0.09191072041586122, 0.12013738093276176 ], "twoSidedFisherExactP": 3.56291448691478e-46 }, "flow": { "portalSamples": { "breast_msk_2026": 6318, "breast_msk_2025": 3879 }, "distinctPatients": 5916, "excludedSamples": { "patientInEarlierMskSeries": 3452, "sampleOfPatientListedInFirstStudy": 1821, "notSequenced": 0, "otherCancerType": 3, "otherSpecimenType": 201, "panelNotListed": 0, "laterSampleOfSelectedPatient": 588 }, "selectedPatients": 4132, "selectedByStudy": { "breast_msk_2026": 3904, "breast_msk_2025": 228 }, "sampleSelectionUsesOutcomes": false, "esr1RecordsOfOtherConsequence": 0 }, "limitations": [ { "en": "Not an external cohort: same institution, referral pattern, assay family and calling pipeline as A2. Only the patients differ.", "ko": "외부 코호트가 아닙니다. 기관, 의뢰 경로, 검사법 계열, 변이 판정 과정이 A2와 같고 환자만 다릅니다." }, { "en": "These studies carry no receptor subtype, so the comparison covers all breast cancer. A2 reported its main contrast in hormone receptor-positive, HER2-negative samples; the two proportions are not the same quantity.", "ko": "이 자료에는 수용체 아형이 없어 유방암 전체를 비교했습니다. A2의 주요 비교는 호르몬 수용체 양성·HER2 음성 표본이었으므로 두 비율은 같은 양이 아닙니다." }, { "en": "Specimen type stands in for disease course. Metastatic specimens come from patients with more prior endocrine therapy; treatment history is not available, and no acquisition or treatment effect is claimed.", "ko": "검체 유형은 병의 경과를 대신하는 표지입니다. 전이 검체는 내분비 치료를 더 많이 받은 환자에게서 나오며 치료 이력은 자료에 없습니다. 변이 획득이나 치료 효과를 주장하지 않습니다." }, { "en": "One specimen per patient chosen by sample identifier; 588 further specimens of selected patients were not used. A specimen without a reported mutation is non-detection, not proven absence.", "ko": "환자마다 검체 번호 순으로 하나만 골랐고 같은 환자의 다른 검체 588개는 쓰지 않았습니다. 변이 미보고는 미검출일 뿐 부재의 증명이 아닙니다." }, { "en": "Patients of three MSK series already analysed here were removed by patient identifier (3,452 specimens). A patient registered under another identifier would not be detected.", "ko": "이미 분석한 세 MSK 자료의 환자는 환자번호로 제외했습니다(검체 3,452개). 다른 번호로 등록된 동일인은 찾아내지 못합니다." } ], "sources": [ { "label": "cBioPortal study: CCNE1 Amplifications in Breast Cancer (MSK, 2026)", "url": "https://www.cbioportal.org/study/summary?id=breast_msk_2026" }, { "label": "cBioPortal study: Breast Cancer (MSK, Nat Genet 2025)", "url": "https://www.cbioportal.org/study/summary?id=breast_msk_2025" }, { "label": "Gupta et al., Nat Genet 2025 (PMID 40379787)", "url": "https://pubmed.ncbi.nlm.nih.gov/40379787/" } ], "plan": { "path": "docs/CV-A2-MSK-PLAN-2026-10-07.json", "sha256": "47bc2816513f948cfe8e10febfdf120860213620bfe8e5b5cac6b8a0755f69c9" }, "inputs": { "path": "data/cohort-validations/2026-10-07/CV-A2-MSK/outcomes/manifest.json", "sha256": "3bdd97e10c641c673825063b82a7e92dedea4bc3729a895c8bd144b694636113" }, "rawResult": { "path": "data/cohort-validations/2026-10-07/CV-A2-MSK/run/stats-result.json", "sha256": "a250692a092f77f9e095286ee60bdc2d6aa9449c46a015ceba1443b42f925332" }, "implementation": { "path": "scripts/run-cohort-a2-msk.py", "sha256": "0470d7ca51ca0ae9b18996b09e5de4379b751dfcdb02a3ec506ec5d883128088" }, "independence": { "path": "data/cohort-validations/2026-10-07/CV-A2-MSK/independence.json", "sha256": "d1c2d3f3d226c1cfdb2fd9e720f1f1d4270c233aa05d3297e2f372f25458b0c9" }, "report": { "path": "data/cohort-validations/2026-10-07/CV-A2-MSK/result.json", "sha256": "7534e3b525562b25cf82b834ecd83825b12769999c9f87ef1ce9c5dcc1993817" } }, { "id": "CV-A7-OM-20261007", "parentAnalysisId": "A7", "status": "completed", "scope": "external-patient-cohort-descriptive-evaluation", "conclusion": "supported", "countingKey": "A7|ORIGIMED-2020:colorectal-adenocarcinoma", "by": "Claude", "added": "2026-10-07", "executedAtUtc": "2026-10-06T17:19:48.568550+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 amplification by RAS/BRAF status in the external OrigiMed colorectal cohort", "ko": "외부 OrigiMed 대장암 코호트의 RAS/BRAF 상태별 ERBB2 증폭" }, "question": { "en": "Among colorectal adenocarcinoma patients sequenced by a different laboratory and panel than A7, is high-level ERBB2 amplification more frequent in tumours without a RAS or BRAF V600E hotspot mutation than in tumours with one?", "ko": "A7과 다른 검사실·패널로 분석한 대장 선암 환자에서, 고수준 ERBB2 증폭이 RAS 또는 BRAF V600E 주요 변이가 있는 종양보다 없는 종양에서 더 흔한가" }, "summary": { "en": "The prespecified direction was supported. ERBB2 amplification was reported in 22 of 553 patients without a RAS or BRAF hotspot mutation and 5 of 667 patients with one. The proportions are close to those of A7 in a different country, laboratory and panel. Amplification is uncommon in both groups, and this is a molecular co-occurrence, not a treatment finding.", "ko": "사전에 정한 비교 방향이 지지됐습니다. ERBB2 증폭은 RAS·BRAF 주요 변이가 없는 환자 553명 중 22명, 있는 환자 667명 중 5명에서 보고됐습니다. 나라·검사실·패널이 다른 자료인데도 A7과 비슷한 비율입니다. 두 군 모두 증폭은 드물며, 이는 분자 변화가 함께 나타나는 양상일 뿐 치료 효과를 뜻하지 않습니다." }, "cohorts": [ { "role": "wildtype", "studyId": "pan_origimed_2020", "label": { "en": "OrigiMed colorectal · no RAS or BRAF hotspot mutation", "ko": "OrigiMed 대장암 · RAS·BRAF 주요 변이 없음" }, "patients": 553, "erbb2Amplified": 22, "proportion": 0.039783001808318265, "ci95": [ 0.02641669747667786, 0.05949906555220128 ] }, { "role": "mutant", "studyId": "pan_origimed_2020", "label": { "en": "OrigiMed colorectal · RAS or BRAF hotspot mutation", "ko": "OrigiMed 대장암 · RAS·BRAF 주요 변이 있음" }, "patients": 667, "erbb2Amplified": 5, "proportion": 0.0074962518740629685, "ci95": [ 0.003206077923905205, 0.017426902698709744 ] } ], "primary": { "riskDifference": 0.032286749934255295, "ci95": [ 0.01563514588878608, 0.05246418193328507 ], "fisherP": 0.000130869055256352 }, "flow": { "portalSamples": 10194, "profiledSamples": 10194, "labelledSamples": 1220, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 0, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 1220, "specimenTypes": { "Metastasis": 160, "Primary": 1047, "Recurrent": 13 }, "sampleSelectionUsesOutcomes": false, "completePatients": 1220, "missingCopyNumberPatients": 0 }, "limitations": [ { "en": "Patients were referred for clinical sequencing at one commercial laboratory in China. Most specimens are primary tumours (1,047 of 1,220), whereas A7 enrolled patients with metastatic disease; the populations are related, not identical.", "ko": "환자들은 중국의 한 민간 검사실에 임상 유전체 검사를 의뢰한 사람들입니다. 검체 1,220개 중 1,047개가 원발 종양이며, A7은 전이성 환자를 모은 자료입니다. 두 집단은 관련은 있지만 같지 않습니다." }, { "en": "ERBB2 amplification is the source laboratory's panel-based category 2, not the immunohistochemistry and in situ hybridisation definition of HER2-positive disease used in trials.", "ko": "ERBB2 증폭은 원자료 검사실이 패널에서 판정한 범주 2이며, 임상시험이 쓰는 면역조직화학·제자리부합법 기준의 HER2 양성과 다릅니다." }, { "en": "Only 27 tumours were amplified, 5 of them with a RAS or BRAF hotspot mutation. No adjustment for tumour side, microsatellite status, stage or treatment; one prespecified test.", "ko": "증폭 종양은 27개뿐이고 그중 5개에는 RAS·BRAF 주요 변이가 함께 있었습니다. 종양 위치, 현미부수체 상태, 병기, 치료를 보정하지 않았고 사전에 정한 검정은 하나입니다." }, { "en": "The direction was expected from published reports and from A7. The copy-number file had been frozen earlier for another evaluation of this study; colorectal values were not read before the plan was locked, and the mutation file was retrieved after the lock.", "ko": "방향은 기존 문헌과 A7에서 예상된 것입니다. 복제수 파일은 같은 자료의 다른 평가를 위해 먼저 보관돼 있었지만 대장암 값은 계획을 고정하기 전에 읽지 않았고, 변이 파일은 고정 뒤에 받았습니다." }, { "en": "No selected identifier matches the A7 patient list or the gastric and breast patients used from this study, but anonymised records cannot prove that every donor differs.", "ko": "선택한 식별자 중 A7 환자 목록이나 같은 자료에서 쓴 위암·유방암 환자와 일치하는 것은 없지만, 익명화된 기록으로 모든 환자가 다른 사람임을 입증할 수는 없습니다." } ], "sources": [ { "label": "cBioPortal study: China Pan-cancer (OrigiMed, Nature 2022)", "url": "https://www.cbioportal.org/study/summary?id=pan_origimed_2020" }, { "label": "Wu et al., Nature 2022 (PMID 35871175)", "url": "https://pubmed.ncbi.nlm.nih.gov/35871175/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/dca75cb3f32b82d54a6f78bf0a6323e5b975aca1/public/pan_origimed_2020" } ], "plan": { "path": "docs/CV-A7-OM-PLAN-2026-10-07.json", "sha256": "99ada1d6c4e1b2eaa83ab4d17bd5c5b8f49ca7a922192956622f7083db153f30" }, "inputs": { "path": "data/cohort-validations/2026-10-07/CV-A7-OM/outcomes/manifest.json", "sha256": "8c0e73c4cac7d5dfb64683d2449475c78a9e8e5567af0cc3d1b5c47f36583706" }, "rawResult": { "path": "data/cohort-validations/2026-10-07/CV-A7-OM/run/stats-result.json", "sha256": "4197cedd412b257923f16ccd04330d2570e82177f46a3e1fb76b7b0cea425b36" }, "implementation": { "path": "scripts/run-cohort-a7-origimed.py", "sha256": "2f898b4491515d297e49ef32bea7c6062d60e71c7575068ba7103699909f78a3" }, "independence": { "path": "data/cohort-validations/2026-10-07/CV-A7-OM/independence.json", "sha256": "80511fcea46e785839afcd1099e21958d779280f58dfcdf5082f88b7671e91e7" }, "report": { "path": "data/cohort-validations/2026-10-07/CV-A7-OM/result.json", "sha256": "5a49330731dcb9a16d401be1cc23aa5bca0404157d28b637c44f658c3fee4b6a" } }, { "id": "CV-A7-SYSUCC-20261007", "parentAnalysisId": "A7", "status": "completed", "scope": "independent-patient-cohort-descriptive-evaluation", "conclusion": "inconclusive", "countingKey": "A7|SYSUCC-CRC-2022:whole-exome-one-sample-per-patient", "by": "Claude", "added": "2026-10-07", "executedAtUtc": "2026-10-06T17:16:58.335495+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 amplification by RAS/BRAF status in the SYSUCC colorectal cohort", "ko": "SYSUCC 대장암 코호트의 RAS/BRAF 상태별 ERBB2 증폭" }, "question": { "en": "In this separately collected colorectal cancer cohort, is high-level ERBB2 amplification more frequent in tumours without a RAS or BRAF V600E mutation than in tumours with one?", "ko": "따로 수집된 이 대장암 코호트에서, RAS·BRAF V600E 변이가 없는 종양에 ERBB2 고도 증폭이 변이가 있는 종양보다 더 흔한가" }, "summary": { "en": "Inconclusive. Amplification was reported in 28 of 739 tumours without a hotspot mutation and 4 of 276 with one. The point estimate lies in the A7 direction, but the interval for the difference includes zero and the exact test did not meet the prespecified threshold.", "ko": "판단 불가입니다. 주요 변이가 없는 종양 739건 중 28건, 있는 종양 276건 중 4건에서 증폭이 보고됐습니다. 점추정은 A7과 같은 방향이지만 차이의 구간이 0을 포함하고 정확 검정이 사전에 정한 기준에 이르지 못했습니다." }, "cohorts": [ { "role": "evaluated", "studyId": "crc_sysucc_2022", "label": { "en": "SYSUCC colorectal · ChangKang project", "ko": "SYSUCC colorectal · ChangKang project" }, "patients": 1015 } ], "groups": [ { "role": "wildtype", "patients": 739, "erbb2Amplified": 28, "proportion": 0.037889039242219216, "wilson95CI": [ 0.02634237646857688, 0.05421513430323178 ] }, { "role": "mutant", "patients": 276, "erbb2Amplified": 4, "proportion": 0.014492753623188406, "wilson95CI": [ 0.005650001281796864, 0.036664882547769756 ] } ], "primary": { "endpoint": "ERBB2_high_level_amplification", "contrast": "wildtype_minus_mutant", "riskDifference": 0.02339628561903081, "newcombeWilson95CI": [ -0.0016022887854522314, 0.04196334378429771 ], "twoSidedFisherExactP": 0.06827552791257548, "contingencyTable": [ [ 28, 711 ], [ 4, 272 ] ], "tableRows": [ "wildtype", "mutant" ], "tableColumns": [ "ERBB2_amplified", "not_amplified" ], "numberOfPrimaryTests": 1 }, "flow": { "clinicalSamples": 1015, "profiledSamples": 1015, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 0, "notWholeExomeForBoth": 0, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 1015, "selectionUsesOutcomes": false }, "limitations": [ { "en": "The share of tumours with a RAS or BRAF hotspot mutation in this public mutation file (about a quarter) is lower than usually reported for colorectal cancer. If some mutant tumours are missing calls they are counted as wild-type, which biases toward no difference.", "ko": "이 공개 변이 파일에서 RAS·BRAF 주요 변이가 있는 종양의 비율(약 4분의 1)은 대장암에서 보통 보고되는 것보다 낮습니다. 변이가 누락된 종양은 변이 없음으로 집계되므로 차이가 없는 쪽으로 치우칩니다." }, { "en": "Whole-exome sequencing and exome-derived discrete copy-number calls here; a targeted panel in A7. Amplification is the public discrete call, not the immunohistochemistry and in-situ hybridisation definition used in trials.", "ko": "여기서는 전장 엑솜과 엑솜에서 얻은 복제수 판정을, A7에서는 표적 패널을 썼습니다. 증폭은 공개 자료의 판정이며 임상시험의 면역조직화학·제자리부합법 기준이 아닙니다." }, { "en": "A single Chinese institution with a different stage mix from the metastatic MSK series; one prespecified test without adjustment for tumour side, microsatellite status or stage.", "ko": "중국의 한 기관 자료이며 전이성 환자만 모은 MSK 자료와 병기 구성이 다릅니다. 종양 위치, 현미부수체 상태, 병기를 보정하지 않은 사전 지정 검정 하나입니다." }, { "en": "The mutation and copy-number files are several hundred megabytes. They were verified against their pinned hashes while downloading; the repository stores only the rows for the four genes, so the full files cannot be re-hashed from the repository.", "ko": "변이·복제수 파일은 수백 메가바이트입니다. 내려받으며 고정된 해시와 대조했고 저장소에는 네 유전자의 행만 보관하므로, 저장소만으로 전체 파일의 해시를 다시 확인할 수는 없습니다." }, { "en": "No selected identifier matches the MSK series used for A7; donor overlap across anonymised studies cannot be excluded in principle. A molecular co-occurrence pattern is not a treatment effect.", "ko": "선택한 식별자 중 A7에 쓴 MSK 자료와 일치하는 것은 없으나, 익명화된 연구 사이의 환자 중복을 원리적으로 배제할 수는 없습니다. 분자 소견이 함께 나타나는 양상은 치료 효과가 아닙니다." } ], "sources": [ { "label": "cBioPortal study: Colorectal Cancer, ChangKang Project (SYSUCC, Nat Commun 2022)", "url": "https://www.cbioportal.org/study/summary?id=crc_sysucc_2022" }, { "label": "Source publication (PMID 35487942)", "url": "https://pubmed.ncbi.nlm.nih.gov/35487942/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/47c8bf9cda53cfb0918dd7399feb1e0d1df4a154/public/crc_sysucc_2022" } ], "plan": { "path": "docs/CV-A7-SYSUCC-PLAN-2026-10-07.json", "sha256": "8039ee2918289763229cdf898f0143c0172ee75a1afc49a5a613ed0de135c8a7" }, "inputs": { "path": "data/cohort-validations/2026-10-07/CV-A7-SYSUCC/outcomes/manifest.json", "sha256": "7fc188aa6cdbb6f00e80d2f834a6be1468ba12a3c1a0573ec921a1deda694c22" }, "rawResult": { "path": "data/cohort-validations/2026-10-07/CV-A7-SYSUCC/run/stats-result.json", "sha256": "5bea522b2fb130ecc2ef8801ef0ac22f71e54d45617b06292c5aa99c4105e1c4" }, "implementation": { "path": "scripts/run-cohort-a7.py", "sha256": "0ed413244e6833a3ef73e4116832066bb8d7f8451d3d57f45b889f962ee53013" }, "independence": { "path": "data/cohort-validations/2026-10-07/CV-A7-SYSUCC/independence.json", "sha256": "1410000382728da48d2d049147607d58c51cccb5c6ad5e1204cf621fe3089533" }, "report": { "path": "data/cohort-validations/2026-10-07/CV-A7-SYSUCC/result.json", "sha256": "f86a47924c337be1263f66878a472d2953590b534b7d1ed3b3fe02d5efaaadd9" } }, { "id": "CV-A7-MSKDH-20261007", "parentAnalysisId": "A7", "status": "completed", "scope": "same-institution-patient-disjoint-descriptive-evaluation", "externalCohort": false, "conclusion": "supported", "countingKey": "A7|MSK-CRC-DATAHUB-2019-2021:patient-disjoint-three-studies", "by": "Claude", "added": "2026-10-07", "executedAtUtc": "2026-10-06T22:58:32.114423+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "same_institution_patient_disjoint", "independenceNote": { "en": "Same institution and assay family as A7. The patients are different people: anyone whose hospital-wide identifier appears in an MSK study already analysed here was removed before selection. This is not an external cohort.", "ko": "A7과 같은 기관, 같은 계열의 분석법입니다. 환자는 서로 다른 사람입니다. 이미 분석한 MSK 연구에 병원 공통 환자번호가 있는 사람은 선택 전에 모두 뺐습니다. 외부 코호트가 아닙니다." }, "title": { "en": "ERBB2 amplification by RAS/BRAF status in further MSK colorectal patients", "ko": "다른 MSK 대장암 환자의 RAS/BRAF 상태별 ERBB2 증폭" }, "question": { "en": "Among MSK colorectal cancer patients of three further studies who appear in no MSK study already analysed here, is high-level ERBB2 amplification more frequent in tumours without a RAS or BRAF V600E mutation than in tumours with one?", "ko": "이미 분석한 MSK 연구에 없는, 다른 세 연구의 MSK 대장암 환자에서 RAS·BRAF V600E 변이가 없는 종양에 ERBB2 고도 증폭이 변이가 있는 종양보다 더 흔한가" }, "summary": { "en": "The prespecified direction was supported in 717 patients not analysed before: amplification in 14 of 354 tumours without a hotspot mutation and 4 of 363 with one. Twenty of them carry a study-specific identifier, so for those the comparison with earlier MSK studies could not be made. These are other patients of the same institution, so this shows the A7 pattern is not confined to the original 1,099 patients; it is not evidence from a different institution.", "ko": "이전에 분석하지 않은 환자 717명에서 사전에 정한 방향이 지지됐습니다. 주요 변이가 없는 종양 354건 중 14건, 있는 종양 363건 중 4건에서 증폭이 있었습니다. 이 가운데 20명은 연구 고유 번호만 있어 이전 MSK 연구와의 대조를 하지 못했습니다. 같은 기관의 다른 환자들이므로 A7 양상이 처음 1,099명에만 국한되지 않음을 보여 주지만, 다른 기관의 근거는 아닙니다." }, "cohorts": [ { "role": "evaluated", "studyId": "crc_eo_2020", "label": { "en": "MSK colorectal · three DataHub studies, patients outside earlier MSK series", "ko": "MSK colorectal · three DataHub studies, patients outside earlier MSK series" }, "patients": 567 }, { "role": "evaluated", "studyId": "crc_apc_impact_2020", "label": { "en": "MSK colorectal · three DataHub studies, patients outside earlier MSK series", "ko": "MSK colorectal · three DataHub studies, patients outside earlier MSK series" }, "patients": 117 }, { "role": "evaluated", "studyId": "rectal_msk_2019", "label": { "en": "MSK colorectal · three DataHub studies, patients outside earlier MSK series", "ko": "MSK colorectal · three DataHub studies, patients outside earlier MSK series" }, "patients": 33 } ], "groups": [ { "role": "wildtype", "patients": 354, "erbb2Amplified": 14, "proportion": 0.03954802259887006, "wilson95CI": [ 0.023701728010641392, 0.06528030030332524 ] }, { "role": "mutant", "patients": 363, "erbb2Amplified": 4, "proportion": 0.011019283746556474, "wilson95CI": [ 0.004293297407546585, 0.027986202458039847 ] } ], "primary": { "endpoint": "ERBB2_high_level_amplification", "contrast": "wildtype_minus_mutant", "riskDifference": 0.028528738852313586, "newcombeWilson95CI": [ 0.005312766274387634, 0.05512552452449113 ], "twoSidedFisherExactP": 0.016580501443665838, "contingencyTable": [ [ 14, 340 ], [ 4, 359 ] ], "tableRows": [ "wildtype", "mutant" ], "tableColumns": [ "ERBB2_amplified", "not_amplified" ], "numberOfPrimaryTests": 1 }, "flow": { "studies": { "crc_eo_2020": { "clinicalSamples": 1516, "profiledSamples": 1516, "selectedPatients": 567 }, "crc_apc_impact_2020": { "clinicalSamples": 471, "profiledSamples": 471, "selectedPatients": 117 }, "rectal_msk_2019": { "clinicalSamples": 339, "profiledSamples": 334, "selectedPatients": 33 } }, "earlierMskPatients": 8046, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 5, "panelMissingRequiredGene": 3, "patientInEarlierMskSeries": 1515, "patientTakenFromEarlierListedStudy": 54, "additionalSamplesOfSelectedPatients": 32 }, "selectedPatients": 717, "selectionUsesOutcomes": false }, "limitations": [ { "en": "Not an external cohort: same institution and assay family as A7. It tests whether the pattern holds in other patients there, not whether it generalises elsewhere.", "ko": "외부 코호트가 아닙니다. A7과 같은 기관, 같은 계열의 분석법입니다. 그 기관의 다른 환자에서도 양상이 유지되는지를 본 것이며 다른 곳으로 일반화되는지를 본 것이 아닙니다." }, { "en": "The three studies were assembled for different purposes (early-onset disease, APC status, rectal cancer); the pooled patients are not a consecutive series. Eighteen amplified tumours in total.", "ko": "세 연구는 서로 다른 목적(조기 발병, APC 상태, 직장암)으로 모은 자료여서 합친 환자가 연속 등록 환자군이 아닙니다. 증폭 종양은 모두 18건입니다." }, { "en": "A fourth study (rectal_msk_2022) was dropped before the plan was locked because a control-gene check showed its copy-number profile returns no per-sample calls; no outcome data were used for that decision.", "ko": "네 번째 연구(rectal_msk_2022)는 계획을 잠그기 전에 뺐습니다. 대조 유전자로 확인하니 복제수 자료가 검체별 값을 주지 않았기 때문이며, 이 결정에 결과 자료는 쓰지 않았습니다." }, { "en": "Patient disjointness rests on the hospital-wide identifier. Twenty of the 717 analysed patients, all from the 2019 rectal study, carry a study-specific identifier instead, so it cannot be checked whether they also appear in another MSK study. They remain in this analysis as locked, but are not counted toward the patient-record total. A person given two hospital-wide identifiers would also go undetected.", "ko": "환자 중복 여부는 병원 공통 환자번호에 의존합니다. 분석한 717명 중 20명(모두 2019년 직장암 연구)은 연구 고유 번호만 있어 다른 MSK 연구에 같은 환자가 있는지 확인할 수 없습니다. 잠근 계획대로 이 분석에는 포함돼 있지만 환자 기록 전체 수에는 세지 않았습니다. 한 사람이 병원 공통 번호 두 개를 받았다면 역시 걸러지지 않습니다." }, { "en": "Discrete copy-number call from a targeted panel, not the immunohistochemistry and in-situ hybridisation definition used in trials. One prespecified test without adjustment. A molecular co-occurrence pattern is not a treatment effect.", "ko": "표적 패널의 복제수 판정이며 임상시험의 면역조직화학·제자리부합법 기준이 아닙니다. 보정 없는 사전 지정 검정 하나입니다. 분자 소견이 함께 나타나는 양상은 치료 효과가 아닙니다." } ], "sources": [ { "label": "cBioPortal studies: crc_eo_2020, crc_apc_impact_2020, rectal_msk_2019", "url": "https://www.cbioportal.org/study/summary?id=crc_eo_2020,crc_apc_impact_2020,rectal_msk_2019" }, { "label": "Source publications (PMID 34405229, 32730818, 31591597)", "url": "https://pubmed.ncbi.nlm.nih.gov/?term=34405229+32730818+31591597" } ], "plan": { "path": "docs/CV-A7-MSKDH-PLAN-2026-10-07.json", "sha256": "019dd7858d7205f5c6c47ff9a22ea0c382c3a21027fc191737c31dcb2a505347" }, "inputs": { "path": "data/cohort-validations/2026-10-07/CV-A7-MSKDH/outcomes/manifest.json", "sha256": "de5ce1c90bedcb8bf94afe81f130f02b8b66101d036256eecaa9ad6cedd2e5f0" }, "rawResult": { "path": "data/cohort-validations/2026-10-07/CV-A7-MSKDH/run/stats-result.json", "sha256": "4ced33b57a74cb2ee447e693051984bdff1be9c4ebb3293ad12f3f9cb5389034" }, "implementation": { "path": "scripts/run-cohort-a7-mskdh.py", "sha256": "8e29c8d6ae6313b9af19a7ab64006806cf375c1335399e3ad1ec940b8ebc9654" }, "independence": { "path": "data/cohort-validations/2026-10-07/CV-A7-MSKDH/independence.json", "sha256": "5c7988533765855630e193edef6e49aec30fdfbb060ed6af71e6a62aaa0ca919" }, "acquisitionScript": { "path": "scripts/fetch-frozen-datahub-multi.py", "sha256": "787ebd262754905e96d4699f01a2bd53ce2f9d18ccba42ebf5c98259af5cd276" }, "patientRecordCounting": { "selectedPatients": 717, "countedInHeadline": 697, "notCounted": 20, "rule": "hospital-wide-msk-identifier-only" }, "report": { "path": "data/cohort-validations/2026-10-07/CV-A7-MSKDH/result.json", "sha256": "35a824a9e7d4253a8a371c81855e056d478895fce28f35f866bd299066269699" } }, { "id": "CV-A7-ACICAM-20261011", "parentAnalysisId": "A7", "status": "completed", "scope": "independent-patient-cohort-descriptive-evaluation", "conclusion": "inconclusive", "countingKey": "A7|SIDRA-LUMC-AC-ICAM-2022:whole-exome-one-sample-per-patient", "by": "Claude", "added": "2026-10-11", "executedAtUtc": "2026-10-11T00:21:07.050709+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 amplification by RAS/BRAF status in the Sidra-LUMC AC-ICAM colon cohort", "ko": "Sidra-LUMC AC-ICAM 결장암 코호트의 RAS/BRAF 상태별 ERBB2 증폭" }, "question": { "en": "In this separately collected colon cancer cohort, is high-level ERBB2 amplification more frequent in tumours without a RAS or BRAF V600E mutation than in tumours with one?", "ko": "따로 수집된 이 결장암 코호트에서, RAS·BRAF V600E 변이가 없는 종양에 ERBB2 고도 증폭이 변이가 있는 종양보다 더 흔한가" }, "summary": { "en": "Inconclusive. Amplification was reported in 0 of 114 tumours without a hotspot mutation and 2 of 167 with one. With two amplified tumours in the whole cohort the comparison carries almost no information; the interval for the difference includes zero and the exact test did not meet the prespecified threshold.", "ko": "판단 불가입니다. 주요 변이가 없는 종양 114건 중 0건, 있는 종양 167건 중 2건에서 증폭이 보고됐습니다. 코호트 전체에서 증폭 종양이 2건뿐이라 비교가 알려 주는 바가 거의 없습니다. 차이의 구간이 0을 포함하고 정확 검정이 사전에 정한 기준에 이르지 못했습니다." }, "cohorts": [ { "role": "evaluated", "studyId": "coad_silu_2022", "label": { "en": "Sidra-LUMC colon · AC-ICAM", "ko": "Sidra-LUMC colon · AC-ICAM" }, "patients": 281 } ], "groups": [ { "role": "wildtype", "patients": 114, "erbb2Amplified": 0, "proportion": 0, "wilson95CI": [ 0, 0.03259853415884163 ] }, { "role": "mutant", "patients": 167, "erbb2Amplified": 2, "proportion": 0.011976047904191617, "wilson95CI": [ 0.003290431921319656, 0.042608607309690974 ] } ], "primary": { "endpoint": "ERBB2_high_level_amplification", "contrast": "wildtype_minus_mutant", "riskDifference": -0.011976047904191617, "newcombeWilson95CI": [ -0.042608607309690974, 0.02175975435849491 ], "twoSidedFisherExactP": 0.5160650737163193, "contingencyTable": [ [ 0, 114 ], [ 2, 165 ] ], "tableRows": [ "wildtype", "mutant" ], "tableColumns": [ "ERBB2_amplified", "not_amplified" ], "numberOfPrimaryTests": 1 }, "flow": { "clinicalSamples": 348, "profiledSamples": 348, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 0, "notWholeExomeForBoth": 67, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 281, "selectionUsesOutcomes": false }, "limitations": [ { "en": "Only two tumours carried the amplification call, both in the group with a hotspot mutation. Counts this small cannot show a direction; the result neither supports nor contradicts A7.", "ko": "증폭 판정을 받은 종양은 2건뿐이고 둘 다 주요 변이가 있는 집단에 있습니다. 이만큼 적은 수로는 방향을 알 수 없으며, 이 결과는 A7을 지지하지도 반박하지도 않습니다." }, { "en": "A single Dutch institution, colon cancer only (no rectal cancer) and mostly resected primary tumours across stages, unlike the metastatic MSK series; one prespecified test without adjustment for tumour side, microsatellite status or stage.", "ko": "네덜란드의 한 기관 자료이고 결장암만 담았으며(직장암 없음) 대부분 여러 병기의 절제된 원발 종양이어서, 전이성 환자만 모은 MSK 자료와 다릅니다. 종양 위치, 현미부수체 상태, 병기를 보정하지 않은 사전 지정 검정 하나입니다." }, { "en": "Whole-exome sequencing and exome-derived discrete copy-number calls here; a targeted panel in A7. Amplification is the public discrete call, not the immunohistochemistry and in-situ hybridisation definition used in trials.", "ko": "여기서는 전장 엑솜과 엑솜에서 얻은 복제수 판정을, A7에서는 표적 패널을 썼습니다. 증폭은 공개 자료의 판정이며 임상시험의 면역조직화학·제자리부합법 기준이 아닙니다." }, { "en": "The mutation and copy-number files are up to a few hundred megabytes. They were verified against their pinned hashes while downloading; the repository stores only the rows for the four genes, so the full files cannot be re-hashed from the repository.", "ko": "변이·복제수 파일은 크게는 수백 메가바이트입니다. 내려받으며 고정된 해시와 대조했고 저장소에는 네 유전자의 행만 보관하므로, 저장소만으로 전체 파일의 해시를 다시 확인할 수는 없습니다." }, { "en": "No selected identifier matches the MSK series used for A7; donor overlap across anonymised studies cannot be excluded in principle. A molecular co-occurrence pattern is not a treatment effect.", "ko": "선택한 식별자 중 A7에 쓴 MSK 자료와 일치하는 것은 없으나, 익명화된 연구 사이의 환자 중복을 원리적으로 배제할 수는 없습니다. 분자 소견이 함께 나타나는 양상은 치료 효과가 아닙니다." } ], "sources": [ { "label": "cBioPortal study: Colon Cancer (Sidra-LUMC AC-ICAM, Nat Med 2023)", "url": "https://www.cbioportal.org/study/summary?id=coad_silu_2022" }, { "label": "Source publication (PMID 37202560)", "url": "https://pubmed.ncbi.nlm.nih.gov/37202560/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/dca75cb3f32b82d54a6f78bf0a6323e5b975aca1/public/coad_silu_2022" } ], "plan": { "path": "docs/CV-A7-ACICAM-PLAN-2026-10-11.json", "sha256": "5549774c2cfdddad3598c9901139dd3831c361058f5ef2241a94864249dcdd1e" }, "inputs": { "path": "data/cohort-validations/2026-10-11/CV-A7-ACICAM/outcomes/manifest.json", "sha256": "0ed471af3584c659163d3b271a6db0a4af0eeee7983ba63b4fe8b95d0f5166a9" }, "rawResult": { "path": "data/cohort-validations/2026-10-11/CV-A7-ACICAM/run/stats-result.json", "sha256": "f23a10cd6c305660dd019b7f612f62020497c8157b269de4fa8de6f4d1232024" }, "implementation": { "path": "scripts/run-cohort-a7-wxs2.py", "sha256": "6c4f6b98b57fdf1f5c2732e1d46447af5486a54bb9f7f3d6c73b5528b71bd05e" }, "independence": { "path": "data/cohort-validations/2026-10-11/CV-A7-ACICAM/independence.json", "sha256": "c807645f1996ca352b8960f91342ac41529283a0fad78041e7dd6a3254a5ac22" }, "report": { "path": "data/cohort-validations/2026-10-11/CV-A7-ACICAM/result.json", "sha256": "94c7d1972455fea0c5ac7f230071cf9b529b01b028e3f95aaa72ccfb47540345" } }, { "id": "CV-A7-CPTAC-20261011", "parentAnalysisId": "A7", "status": "completed", "scope": "independent-patient-cohort-descriptive-evaluation", "conclusion": "inconclusive", "countingKey": "A7|CPTAC2-COLON-2019:whole-exome-one-sample-per-patient", "by": "Claude", "added": "2026-10-11", "executedAtUtc": "2026-10-11T00:21:07.732068+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 amplification by RAS/BRAF status in the CPTAC-2 prospective colon cohort", "ko": "CPTAC-2 전향 결장암 코호트의 RAS/BRAF 상태별 ERBB2 증폭" }, "question": { "en": "In this separately collected colon cancer cohort, is high-level ERBB2 amplification more frequent in tumours without a RAS or BRAF V600E mutation than in tumours with one?", "ko": "따로 수집된 이 결장암 코호트에서, RAS·BRAF V600E 변이가 없는 종양에 ERBB2 고도 증폭이 변이가 있는 종양보다 더 흔한가" }, "summary": { "en": "Inconclusive. No tumour carried the amplification call: 0 of 53 without a hotspot mutation and 0 of 52 with one. The cohort cannot inform the A7 question either way.", "ko": "판단 불가입니다. 증폭 판정을 받은 종양이 없습니다. 주요 변이가 없는 종양 53건 중 0건, 있는 종양 52건 중 0건입니다. 이 코호트로는 A7의 질문에 어느 쪽으로도 답할 수 없습니다." }, "cohorts": [ { "role": "evaluated", "studyId": "coad_cptac_2019", "label": { "en": "CPTAC-2 prospective colon", "ko": "CPTAC-2 prospective colon" }, "patients": 105 } ], "groups": [ { "role": "wildtype", "patients": 53, "erbb2Amplified": 0, "proportion": 0, "wilson95CI": [ 0, 0.0675819885765419 ] }, { "role": "mutant", "patients": 52, "erbb2Amplified": 0, "proportion": 0, "wilson95CI": [ 0, 0.06879223612386236 ] } ], "primary": { "endpoint": "ERBB2_high_level_amplification", "contrast": "wildtype_minus_mutant", "riskDifference": 0, "newcombeWilson95CI": [ -0.06879223612386236, 0.0675819885765419 ], "twoSidedFisherExactP": 1, "contingencyTable": [ [ 0, 53 ], [ 0, 52 ] ], "tableRows": [ "wildtype", "mutant" ], "tableColumns": [ "ERBB2_amplified", "not_amplified" ], "numberOfPrimaryTests": 1 }, "flow": { "clinicalSamples": 110, "profiledSamples": 105, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 5, "notWholeExomeForBoth": 0, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 105, "selectionUsesOutcomes": false }, "limitations": [ { "en": "No tumour among 105 carried the high-level amplification call. With an expected frequency of a few percent this is compatible with chance in a cohort this small, and it may also reflect a conservative public copy-number call; the result neither supports nor contradicts A7.", "ko": "105건 가운데 고도 증폭 판정을 받은 종양이 없습니다. 기대 빈도가 몇 퍼센트인 소견이라 이 크기의 코호트에서는 우연으로도 나올 수 있고, 공개 복제수 판정이 보수적이어서일 수도 있습니다. 이 결과는 A7을 지지하지도 반박하지도 않습니다." }, { "en": "A small multi-centre prospective collection of colon cancer only; five of 110 clinical samples were outside the profiled case list and were not selected. One prespecified test without adjustment for tumour side, microsatellite status or stage.", "ko": "여러 기관에서 전향적으로 모은 작은 결장암 자료입니다. 임상 검체 110건 중 5건은 프로파일된 사례 목록 밖이어서 선택하지 않았습니다. 종양 위치, 현미부수체 상태, 병기를 보정하지 않은 사전 지정 검정 하나입니다." }, { "en": "Whole-exome sequencing and exome-derived discrete copy-number calls here; a targeted panel in A7. Amplification is the public discrete call, not the immunohistochemistry and in-situ hybridisation definition used in trials.", "ko": "여기서는 전장 엑솜과 엑솜에서 얻은 복제수 판정을, A7에서는 표적 패널을 썼습니다. 증폭은 공개 자료의 판정이며 임상시험의 면역조직화학·제자리부합법 기준이 아닙니다." }, { "en": "The mutation and copy-number files are up to a few hundred megabytes. They were verified against their pinned hashes while downloading; the repository stores only the rows for the four genes, so the full files cannot be re-hashed from the repository.", "ko": "변이·복제수 파일은 크게는 수백 메가바이트입니다. 내려받으며 고정된 해시와 대조했고 저장소에는 네 유전자의 행만 보관하므로, 저장소만으로 전체 파일의 해시를 다시 확인할 수는 없습니다." }, { "en": "No selected identifier matches the MSK series used for A7; donor overlap across anonymised studies cannot be excluded in principle. A molecular co-occurrence pattern is not a treatment effect.", "ko": "선택한 식별자 중 A7에 쓴 MSK 자료와 일치하는 것은 없으나, 익명화된 연구 사이의 환자 중복을 원리적으로 배제할 수는 없습니다. 분자 소견이 함께 나타나는 양상은 치료 효과가 아닙니다." } ], "sources": [ { "label": "cBioPortal study: Colon Cancer (CPTAC-2 Prospective, Cell 2019)", "url": "https://www.cbioportal.org/study/summary?id=coad_cptac_2019" }, { "label": "Source publication (PMID 31031003)", "url": "https://pubmed.ncbi.nlm.nih.gov/31031003/" }, { "label": "cBioPortal DataHub, pinned commit", "url": "https://github.com/cBioPortal/datahub/tree/dca75cb3f32b82d54a6f78bf0a6323e5b975aca1/public/coad_cptac_2019" } ], "plan": { "path": "docs/CV-A7-CPTAC-PLAN-2026-10-11.json", "sha256": "8cddf3d9fe157aff07c34775b4612849f1e3a19bd1b3c8c1f4605a242c71c56d" }, "inputs": { "path": "data/cohort-validations/2026-10-11/CV-A7-CPTAC/outcomes/manifest.json", "sha256": "556dadf9ffc3aa93699820c8765221a813af1eb674d3cafd390cc534914397c3" }, "rawResult": { "path": "data/cohort-validations/2026-10-11/CV-A7-CPTAC/run/stats-result.json", "sha256": "e17419ffe89b30f45d3af02aa8602ff52b178e00bfcba191917e2886f62a39a3" }, "implementation": { "path": "scripts/run-cohort-a7-wxs2.py", "sha256": "6c4f6b98b57fdf1f5c2732e1d46447af5486a54bb9f7f3d6c73b5528b71bd05e" }, "independence": { "path": "data/cohort-validations/2026-10-11/CV-A7-CPTAC/independence.json", "sha256": "2612cb51e50b524c3f0e4600703da7dbc7c36f8a5f78c0585e58dd7d2d929a6f" }, "report": { "path": "data/cohort-validations/2026-10-11/CV-A7-CPTAC/result.json", "sha256": "31d4139c64a57b94ce7ee3ff1aae6c769558bcc2ee2950ed7505a108adde9cf1" } }, { "id": "CV-A1-MSK50K-20261022", "parentAnalysisId": "A1", "status": "completed", "scope": "external-patient-cohort-descriptive-evaluation", "conclusion": "supported", "countingKey": "A1|MSK-IMPACT-50K-2026:stomach-adenocarcinoma-vs-invasive-breast", "by": "Claude", "added": "2026-10-22", "executedAtUtc": "2026-10-22T03:24:08.419470+00:00", "externalBiologicalExperiment": false, "predictiveModelValidation": false, "independenceStatus": "collection_independent_with_unresolved_donor_overlap", "title": { "en": "ERBB2 co-amplification in gastric and breast cancer on MSK-IMPACT panels", "ko": "MSK-IMPACT 패널로 본 위암·유방암의 ERBB2 공동증폭" }, "question": { "en": "Among ERBB2-amplified patients sequenced on the same MSK-IMPACT panels, is amplification of at least one of EGFR, MET, FGFR2, KRAS or CCNE1 more frequent in stomach adenocarcinoma than in invasive breast cancer?", "ko": "같은 MSK-IMPACT 패널로 분석한 ERBB2 증폭 환자에서, EGFR·MET·FGFR2·KRAS·CCNE1 중 하나 이상의 공동증폭이 침윤성 유방암보다 위 선암에서 더 흔한가" }, "summary": { "en": "The prespecified direction was supported. Co-amplification was reported in 11 of 35 ERBB2-amplified stomach adenocarcinoma patients and 45 of 709 ERBB2-amplified breast cancer patients, all sequenced on MSK-IMPACT panels. CCNE1 accounted for most gastric events. The earlier MSK gastric series (CV-A3, 3 of 26) was inconclusive; its patients were excluded here. This is a retrospective observational evaluation by the internal team, not a treatment finding.", "ko": "사전에 정한 비교 방향이 지지됐습니다. 같은 MSK-IMPACT 패널로 측정했을 때 공동증폭은 ERBB2 증폭 위 선암 환자 35명 중 11명, ERBB2 증폭 유방암 환자 709명 중 45명에서 보고됐습니다. 위암 쪽은 대부분 CCNE1이었습니다. 앞선 MSK 위암 자료의 평가(CV-A3, 26명 중 3명)는 판단 불가였고, 그 환자들은 이번 평가에서 뺐습니다. 내부 연구팀이 공개 관측 자료를 후향적으로 분석한 결과이며 치료 효과를 뜻하지 않습니다." }, "cohorts": [ { "role": "gastric", "studyId": "msk_impact_50k_2026", "label": { "en": "MSK-IMPACT 50K · stomach adenocarcinoma", "ko": "MSK-IMPACT 50K · 위 선암" }, "patients": 314, "erbb2Amplified": 35, "coamplified": 11, "proportion": 0.3142857142857143, "ci95": [ 0.1855084467426582, 0.47979763612069193 ] }, { "role": "breast", "studyId": "msk_impact_50k_2026", "label": { "en": "MSK-IMPACT 50K · invasive breast cancer", "ko": "MSK-IMPACT 50K · 침윤성 유방암" }, "patients": 5778, "erbb2Amplified": 709, "coamplified": 45, "proportion": 0.06346967559943582, "ci95": [ 0.04777053640916228, 0.08387368498046191 ] } ], "primary": { "riskDifference": 0.25081603868627844, "ci95": [ 0.12043234248665063, 0.417070840844963 ], "fisherP": 0.000016977303432598407 }, "secondary": { "perGeneByCohort": [ { "role": "gastric", "denominator": 35, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 2, "proportion": 0.05714285714285714 }, { "gene": "MET", "coamplifiedPatients": 1, "proportion": 0.02857142857142857 }, { "gene": "FGFR2", "coamplifiedPatients": 0, "proportion": 0 }, { "gene": "KRAS", "coamplifiedPatients": 0, "proportion": 0 }, { "gene": "CCNE1", "coamplifiedPatients": 8, "proportion": 0.22857142857142856 } ], "inference": "descriptive_only_no_per_gene_tests" }, { "role": "breast", "denominator": 709, "perGene": [ { "gene": "EGFR", "coamplifiedPatients": 5, "proportion": 0.007052186177715092 }, { "gene": "MET", "coamplifiedPatients": 3, "proportion": 0.004231311706629055 }, { "gene": "FGFR2", "coamplifiedPatients": 4, "proportion": 0.005641748942172073 }, { "gene": "KRAS", "coamplifiedPatients": 9, "proportion": 0.012693935119887164 }, { "gene": "CCNE1", "coamplifiedPatients": 25, "proportion": 0.03526093088857546 } ], "inference": "descriptive_only_no_per_gene_tests" } ] }, "flow": { "portalSamples": 54331, "cohorts": [ { "role": "gastric", "labelledSamples": 712, "excludedBeforeOutcomes": { "patientInEarlierEgcMskSeries": 380, "notCopyNumberProfiled": 0, "otherSpecimenType": 5, "panelNotListed": 0, "laterSampleOfSelectedPatient": 11, "patientInBothGroups": 2 }, "patientsSelectedBeforeOutcomes": 314, "specimenTypes": { "Metastasis": 77, "Primary": 237 }, "completePatients": 314, "missingCallPatients": 0 }, { "role": "breast", "labelledSamples": 6797, "excludedBeforeOutcomes": { "patientInEarlierEgcMskSeries": 0, "notCopyNumberProfiled": 0, "otherSpecimenType": 38, "panelNotListed": 0, "laterSampleOfSelectedPatient": 979, "patientInBothGroups": 2 }, "patientsSelectedBeforeOutcomes": 5778, "specimenTypes": { "Metastasis": 2658, "Primary": 3120 }, "completePatients": 5778, "missingCallPatients": 0 } ], "sampleSelectionUsesOutcomes": false }, "limitations": [ { "en": "Only 35 ERBB2-amplified gastric patients; the gastric interval is wide. Gene-specific counts are descriptive and overlap.", "ko": "ERBB2 증폭 위암 환자가 35명뿐이어서 위암 쪽 구간이 넓습니다. 유전자별 집계는 기술적 수치이며 서로 겹칩니다." }, { "en": "Same institution and assay family as the EGC-MSK series of CV-A3. Those 380 gastric specimens' patients were removed, but the referral pattern and calling pipeline are shared. The two MSK gastric evaluations point in different directions and are not pooled.", "ko": "CV-A3의 EGC-MSK 자료와 같은 기관·같은 검사법 계열입니다. 그 환자들(검체 380개)은 뺐지만 의뢰 경로와 판정 과정은 같습니다. 두 MSK 위암 평가의 방향이 달라 합치지 않았습니다." }, { "en": "Stomach adenocarcinoma labels only; junctional and esophageal tumours are excluded. Primary specimens are preferred, but 77 gastric and 2,658 breast specimens are metastases.", "ko": "위 선암 표기만 썼고 위식도접합부·식도 종양은 뺐습니다. 원발 검체를 우선했지만 위암 77개, 유방암 2,658개는 전이 검체입니다." }, { "en": "Panel-based discrete copy-number call (category 2), not a clinical HER2 test. Case mix, stage and treatment are not controlled.", "ko": "패널에서 판정한 복제수 범주 2이며 임상 HER2 검사 결과가 아닙니다. 환자 구성, 병기, 치료를 통제하지 않았습니다." }, { "en": "The study is licensed CC BY-NC-ND 4.0; only aggregate results are published. Breast patients already counted in earlier MSK breast evaluations are counted once in the headline patient total.", "ko": "이 자료는 CC BY-NC-ND 4.0 조건이어서 집계 결과만 공개합니다. 앞선 MSK 유방암 평가에서 이미 센 환자는 대표 환자 수에서 한 번만 셉니다." } ], "sources": [ { "label": "cBioPortal study: MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)", "url": "https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026" }, { "label": "Bandlamudi et al., Cancer Cell 2026 (PMID 41895280)", "url": "https://pubmed.ncbi.nlm.nih.gov/41895280/" } ], "plan": { "path": "docs/CV-A1-MSK50K-PLAN-2026-10-22.json", "sha256": "7e5440c7cffda8b2c6dc83313a841612b67c4c2c77ebc543c7be6d67ac090d15" }, "inputs": { "path": "data/cohort-validations/2026-10-22/CV-A1-MSK50K/outcomes/manifest.json", "sha256": "b30c19833aaf5c308e81ac66c7721a8be20b796536b05abfec46f88e01f8b77e" }, "rawResult": { "path": "data/cohort-validations/2026-10-22/CV-A1-MSK50K/run/stats-result.json", "sha256": "620462ec0d640614c498fe2cfa311f372eb42f98bc6afa4613478192bf6774db" }, "implementation": { "path": "scripts/run-cohort-a1-msk50k.py", "sha256": "78f8899ed2f4379a9f19b523297c1795168a6ecb9eccb7f7f9ceb2cf9218975e" }, "independence": { "path": "data/cohort-validations/2026-10-22/CV-A1-MSK50K/independence.json", "sha256": "bc1d548dcac86b26f6ab3397ae3001008d03bfea3ba057746578163a536233e3" }, "report": { "path": "data/cohort-validations/2026-10-22/CV-A1-MSK50K/result.json", "sha256": "82f376fcb8426046c37ef9b8a98efd768c72a633444c62adcbbf16cc0879c0af" } } ], "independentBiologicalValidations": [], "definitions": { "computational": "Unique analyses with complete matching results from a separate implementation on the same named source data. Internal AI-assisted reproduction; not an external research team.", "independent": "External biological experiments performed by qualified institutions. Independent-patient cohort evaluations are recorded separately and do not count as experiments.", "legacy": "A1–A3 execution records preserve their existing dated outputs and script hashes. Historical raw inputs and environment logs were not retained.", "cohort": "Unique prespecified observational questions evaluated on separately collected external patient cohorts, with frozen inputs, source provenance and explicit donor-overlap limitations. Completion and supported/opposite/inconclusive outcomes are counted separately. No new experiment, exact phenotype replication or predictive model validation is implied. One evaluation, marked as such, uses different patients of the same institution as its original analysis; it is patient-disjoint but not an external cohort." } }, "researchCoverage": { "patientRecords": 21479, "studyDatasets": 18, "studies": [ { "studyId": "brca_aurora_2023", "label": "AURORA US · 2023 paired specimens", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=brca_aurora_2023" } ], "patients": 36, "analyses": [ "CV-A5-20261005" ] }, { "studyId": "brca_mbcproject_2022", "label": "MBCproject · December 2021 release", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=brca_mbcproject_2022" } ], "patients": 117, "analyses": [ "CV-A2-20260930" ] }, { "studyId": "brca_metabric", "label": "METABRIC · original 2012", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=brca_metabric" } ], "patients": 1980, "analyses": [ "CV-A1-20260930", "CV-A3" ] }, { "studyId": "breast_msk_2018", "label": "MSK breast · 2018 paired specimens", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=breast_msk_2018" } ], "patients": 42, "analyses": [ "A5" ] }, { "studyId": "breast_msk_2025_2026", "label": "MSK breast · 2025 and 2026 studies, patients outside earlier MSK series", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=breast_msk_2026,breast_msk_2025" } ], "patients": 4132, "analyses": [ "CV-A2-MSK-20261007" ] }, { "studyId": "coad_cptac_2019", "label": "CPTAC-2 prospective colon", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=coad_cptac_2019" } ], "patients": 105, "analyses": [ "CV-A7-CPTAC-20261011" ] }, { "studyId": "coad_silu_2022", "label": "Sidra-LUMC colon · AC-ICAM", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=coad_silu_2022" } ], "patients": 281, "analyses": [ "CV-A7-ACICAM-20261011" ] }, { "studyId": "coadread_dfci_2016", "label": "DFCI colorectal cancer · Cell Reports 2016 (Nurses' Health Study and Health Professionals Follow-up Study)", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=coadread_dfci_2016" } ], "patients": 529, "analyses": [ "A8" ] }, { "studyId": "coadread_genentech", "label": "Genentech colorectal cancer · Nature 2012", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=coadread_genentech" } ], "patients": 72, "analyses": [ "A8" ] }, { "studyId": "crc_msk_2017", "label": "MSK metastatic colorectal · 2017 one sample per patient", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=crc_msk_2017" } ], "patients": 1099, "analyses": [ "A7" ] }, { "studyId": "crc_msk_2026", "label": "MSK colorectal cancer · 2026 portal study", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=crc_msk_2026" } ], "patients": 6513, "analyses": [ "A8" ] }, { "studyId": "crc_msk_datahub_2019_2021", "label": "MSK colorectal · three DataHub studies, patients outside earlier MSK series", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=crc_eo_2020,crc_apc_impact_2020,rectal_msk_2019" } ], "patients": 697, "analyses": [ "CV-A7-MSKDH-20261007" ] }, { "studyId": "crc_sysucc_2022", "label": "SYSUCC colorectal · ChangKang project", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=crc_sysucc_2022" } ], "patients": 1015, "analyses": [ "CV-A7-SYSUCC-20261007" ] }, { "studyId": "egc_msk_2023", "label": "EGC-MSK 2023 · anatomically concordant gastric", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=egc_msk_2023" } ], "patients": 248, "analyses": [ "CV-A3" ] }, { "studyId": "msk_impact_50k_2026", "label": "MSK-IMPACT 50K · 2026", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=msk_impact_50k_2026" } ], "patients": 6814, "analyses": [ "A9", "CV-A1-MSK50K-20261022" ] }, { "studyId": "pan_origimed_2020", "label": "OrigiMed China pan-cancer · 2020", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=pan_origimed_2020" } ], "patients": 2257, "analyses": [ "CV-A1-OM-20261006", "CV-A7-OM-20261007" ] }, { "studyId": "stad_oncosg_2018", "label": "OncoSG · SG/ICGC/HK", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=stad_oncosg_2018" } ], "patients": 108, "analyses": [ "CV-A1-20260930" ] }, { "studyId": "thca_tcga_pan_can_atlas_2018", "label": "TCGA thyroid · papillary carcinoma with recorded thyroid history", "sources": [ { "label": "cBioPortal study", "url": "https://www.cbioportal.org/study/summary?id=thca_tcga_pan_can_atlas_2018" } ], "patients": 434, "analyses": [ "A6" ] } ], "crossStudyDeduplication": { "namespace": "MSK hospital-wide patient identifiers", "studies": [ "breast_msk_2018", "breast_msk_2025_2026", "crc_msk_2017", "crc_msk_2026", "crc_msk_datahub_2019_2021", "egc_msk_2023", "msk_impact_50k_2026" ], "patientsInMoreThanOneStudy": 4995, "recordsRemovedFromHeadline": 5000 }, "definition": { "en": "Patient records with frozen patient-level inputs in completed analyses and external cohort evaluations; duplicates are removed within each study.", "ko": "실행 분석·외부 코호트 평가에서 환자 단위 입력을 확인한 기록 수입니다. 같은 연구 자료 안에서 중복을 제거합니다." }, "limitations": [ { "en": "4995 patient identifier(s) occur in more than one MSK study. They are counted once in the headline total, so the headline is 5000 lower than the sum of the study rows.", "ko": "환자 식별자 4995개가 둘 이상의 MSK 연구에 있습니다. 전체 수에서는 한 번만 세므로 전체 수는 연구별 합보다 5000 적습니다." }, { "en": "Anonymous donors cannot be completely deduplicated across separate studies; this is not a proven count of globally unique people.", "ko": "별도 연구 사이의 익명 환자 중복은 완전히 확인할 수 없습니다. 전 세계적으로 중복 없는 사람 수를 뜻하지 않습니다." }, { "en": "Legacy A1/A2 sample totals, reruns, computational reproductions and metadata-only feasibility checks add no patient records to this metric.", "ko": "기존 A1·A2의 표본 합계, 재실행, 계산 재현 및 자료 확보 가능성 점검은 이 환자 기록 수에 더하지 않습니다." } ] }, "predictionRecords": [ { "id": "PR-001", "version": 1, "by": "Codex (GPT-6)", "added": "2026-10-03", "recordedAt": "2026-10-03T01:59:55+09:00", "informationCutoff": "2026-10-03T01:59:55+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "DRAGON IV에서 병리반응이 개선된 전체 치료 전략은 무사건생존에서도 유리한 방향으로 이어질까", "language": "ko" }, "links": { "pairs": [ "QP-31" ], "units": [ "U-DRAGONIV", "U-MATTERHORN", "U-KN585" ], "nct": "NCT04208347", "trial": "G-DRAGONIV" }, "target": { "program": "gastric", "population": "DRAGON IV/CAP 05의 국소 진행성 위암·위식도접합부 선암 무작위배정 집단; 보고된 선정기준 T3–4aN+M0, 알려진 HER2 양성 제외", "treatment": "수술 전후 camrelizumab + 저용량 rivoceranib + SOX 전체 전략(SOXRC)", "comparator": "SOX 전체 전략", "endpoint": "investigator-assessed co-primary event-free survival (EFS)", "analysisPopulation": "시험이 사전 계획한 전체 무작위배정 EFS 주분석 집단(ITT); 수술 완료·병리반응·바이오마커 하위집단은 대체하지 않음", "selection": "기록 시각 뒤 최초로 공개되는 적격 사전 계획 EFS 주분석(중간 또는 최종)의 주 HR; 유리한 후속 시점으로 교체하지 않음", "endpointDefinitionLimit": "현행 등록은 EFS 이름과 기간만 제공하며 정확한 사건 구성·중간분석 경계는 미확인. 최초 결과 대조 전에 원 프로토콜/SAP와 실제 정의·분모를 확인한다." }, "forecast": { "text": "SOXRC 대 SOX의 EFS HR은 1 미만일 것으로 예상한다.", "quantity": "EFS hazard ratio, SOXRC / SOX", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": null, "uncertainty": "큼; 병리반응에서 EFS로의 이전, 치료 노출·위해, 평가 방식과 분석집단 차이가 남아 있음", "basis": [ "DRAGON IV의 기존 ypT0 병리반응과 수술 도달 양상은 긍정 방향 가설의 배경이다. EFS 결과로 대신 사용하지 않는다.", "MATTERHORN의 EFS 결과는 같은 치료 맥락의 참고지만 다른 약제·항암 구성·집단이므로 효과크기나 성공확률을 옮기지 않는다." ], "counterarguments": [ "KEYNOTE-585는 병리반응 개선이 사전 EFS 성공을 보장하지 않는 반례다.", "DRAGON IV에서 중증 수술 전 치료 관련 위해가 더 많았고, 수술 후 노출은 아직 검토되지 않았다.", "공개라벨·연구자 평가 EFS, 중국 모집단, 중간분석 사건 수와 정확한 지표 정의가 불확실하다." ], "assumptions": [ "처음 공개될 주분석이 같은 전체 전략·원 배정 비교를 유지한다.", "병리반응 개선의 일부가 EFS에도 이어지며 위해·중단이 방향을 뒤집을 만큼 상쇄하지 않는다." ], "changesMind": "적격 EFS 주 HR이 반대 방향이면 최초 예측의 불일치를 기록한다. 정의·집단 차이나 누락은 별도로 기록하며 원 예측을 고쳐 적중으로 바꾸지 않는다.", "nextActionIfSupported": "전체 전략의 EFS 근거를 검토하되 두 약제·수술 전후 단계의 개별 기여와 OS는 별도 질문으로 남긴다.", "nextActionIfOpposed": "병리반응→EFS 이전 가정을 복기하고 위해·수술 후 노출·사건 구성을 다음 질문으로 정리한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개 시각이 recordedAt보다 늦어야 한다. 먼저 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력 보존.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1 또는 반올림으로 방향이 정해지지 않으면 경계값/정밀도 불충분으로 기록한다.", "statisticalRule": "방향 일치와 임상 이득은 별도다. CI·사건 수·유의성/다중성·사전 중간 경계를 그대로 기록한다. 방향 일치만으로 EFS 이득 확정·OS·완치를 주장하지 않는다.", "unassessableRule": "유효한 주 HR·비교 집단·EFS 정의가 없으면 판단 불가 또는 부분 결과 수신으로 유지한다. OS·DFS·수술자 하위집단·병리반응 값으로 대체하지 않는다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험 후속 결과를 독립 생물학적 재현으로 세지 않음." }, "waiting": { "startedAt": "2026-10-03T01:59:55+09:00", "estimatedPrimaryCompletion": { "date": "2026-12", "type": "ESTIMATED" }, "calendarLimit": "등록의 2026-12는 추정 완료 시점이며 공개 예정일이나 대조 완료 마감이 아니다. 변경·자료 없음은 대기로 남긴다." }, "computation": { "status": "not_run", "method": "원문·등록을 기반으로 한 정성적 방향 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "공식 원출처·정해진 PubMed 검색과 일부 웹 검색 범위를 확인했다. 전 세계 모든 언어·학회·기업 공개를 전수 검증하지 않았다.", "내부 날짜·해시는 외부 사전등록이나 정보 비노출의 증명이 아니다. 모델 학습 이력의 미래 정보 노출은 독립 감사하지 못한다.", "이 기록은 예측 훈련이며 외부 실험은 해당 임상시험 연구진의 성과다. 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] }, { "id": "PR-002", "version": 1, "by": "Claude", "added": "2026-10-03", "recordedAt": "2026-10-03T21:10:00+09:00", "informationCutoff": "2026-10-03T21:10:00+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "NATALEE의 리보시클립 추가 보조요법은 다음 전체생존 분석에서 사망 위험 감소를 통계적으로 확인할 수 있을까", "language": "ko" }, "links": { "pairs": [ "QP-14" ], "units": [ "U-NATALEE", "U-monarchE", "U-PALLAS", "U-PENELOPEB" ], "nct": "NCT03701334", "trial": "B-NATALEE" }, "target": { "program": "breast", "population": "NATALEE 무작위배정 집단: II–III기 HR 양성/HER2 음성 조기 유방암(일부 고위험 N0 포함, 상세는 등록 기준)", "treatment": "리보시클립 3년 + 비스테로이드성 아로마타제 억제제(해당 시 생식샘 억제 포함)", "comparator": "같은 내분비요법 단독", "endpoint": "전체생존(무작위배정부터 모든 원인 사망까지; 등록상 2차 평가변수)", "analysisPopulation": "시험이 정한 전체 무작위배정(ITT) 집단; 하위집단·iDFS로 대체하지 않음", "selection": "기록 시각 뒤 처음 공개되는 사전 계획 OS 분석(2026년 10월 ESMO에서 발표가 예고된 장기 추적 OS 분석이 먼저 해당할 것으로 본다)의 주 HR과 그 분석에 대한 시험의 유의성 판정", "endpointDefinitionLimit": "이번 OS 분석이 형식 검정인지 기술적 분석인지, 알파 배분과 경계는 발표 전까지 확인하지 못했다. 대조 전에 발표 자료와 SAP로 확인한다." }, "forecast": { "text": "리보시클립군 대 내분비요법군의 OS HR은 1 미만이겠지만, 이 분석에서 시험의 사전 유의 경계는 넘지 못할 것으로 예상한다.", "quantity": "overall survival hazard ratio, ribociclib + NSAI / NSAI", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": "not_significant", "uncertainty": "중간~큼; 조기 HR 양성 유방암의 사망은 늦게 쌓여 사건 수가 적고, 추적이 길어지며 차이가 커질 수도 줄어들 수도 있다. 분석의 성격(형식 검정 여부)이 미확인이다.", "basis": [ "5년 추적에서 무침습질병생존 이득이 유지됐다(U-NATALEE).", "같은 5년 시점에 함께 공개된 OS는 1 미만 방향이었지만 통계적으로 유의하지 않았고 사건 수가 적었다. 이것은 알려진 배경이며 이번 예측 대상 결과가 아니다.", "보조 CDK4/6 억제제의 결과는 약제·위험군 정의·치료 기간에 따라 갈렸다. monarchE는 장기 추적의 주 OS 분석에서 사전 경계를 넘었고(U-monarchE), PALLAS·PENELOPE-B는 무침습질병생존 이득도 보이지 않았다(U-PALLAS, U-PENELOPEB). 효과크기를 서로 옮기지 않는다.", "기록 시점까지 스폰서의 OS 사전 발표(topline)는 찾지 못했다. 이는 결과의 증거가 아니라 정보 상태의 기록이다." ], "counterarguments": [ "무침습질병생존 차이가 유지되면 6년 무렵 사망 차이가 경계를 넘을 수 있다. monarchE도 장기 추적에서 경계를 넘었다.", "NATALEE는 대상 수가 많아 작은 사망 차이도 검출할 수 있다.", "스폰서가 사전 발표를 하지 않는 관행이 있다면 '발표 없음'은 아무 정보도 주지 않는다." ], "assumptions": [ "다음 공개 OS 분석이 ITT 전체 집단의 원 배정 비교를 유지한다.", "발표에 형식적 유의성 판정이 붙거나, 기술적 분석임이 명시된다." ], "changesMind": "다음 OS 분석이 사전 경계를 넘었다고 보고되면 유의성 예측은 불일치로 기록한다. HR이 1 이상이면 방향도 불일치로 기록한다. 분석 성격을 확인할 수 없으면 유의성 부분은 판단 불가로 남기며 원 예측을 고치지 않는다.", "nextActionIfSupported": "OS 차이가 아직 경계 아래라는 점을 QP-14 판단의 보류 범위와 대조하고, 위험군별 이득 차이를 다음 질문으로 정리한다.", "nextActionIfOpposed": "무침습질병생존 이득이 사망 감소로 이어지는 속도에 대한 가정을 복기하고, monarchE와의 차이(위험군·약제·기간)를 다음 질문으로 정리한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개(학회 초록 공개·발표·스폰서 공지 중 가장 이른 것)가 recordedAt보다 늦어야 한다. 기록 전에 이미 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력을 보존한다. 학회 초록이 발표 전 공개되면 그 시각을 최초 공개로 본다.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "스폰서의 공식 공지와 등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR(리보시클립 + NSAI / NSAI) < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1이거나 반올림으로 방향을 정할 수 없으면 경계값·정밀도 불충분으로 기록한다.", "statisticalRule": "방향·유의성 판정과 임상 이득은 별도다. HR·CI·사건 수·성숙도·다중성·사전 경계를 그대로 기록한다. 방향 일치만으로 생존 이득 확정·완치를 주장하지 않는다.", "unassessableRule": "유효한 ITT OS HR이 없거나 분석 집단·정의가 다르면 판단 불가 또는 부분 결과로 유지한다. iDFS·하위집단 값으로 대체하지 않는다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험의 후속 결과를 독립 재현으로 세지 않음.", "significanceRule": "시험이 이 분석에서 사전 정한 유의 경계를 넘었다고 보고하면 'significant', 넘지 못했다고 보고하거나 형식 검정이 아닌 기술적 분석이라고 밝히면 'not_significant'로 본다. 형식 검정 여부나 경계를 확인할 수 없으면 유의성 부분은 판단 불가로 남긴다. 방향과 유의성은 따로 판정하고 따로 기록한다." }, "waiting": { "startedAt": "2026-10-03T21:10:00+09:00", "estimatedPrimaryCompletion": { "date": "2030-05-29", "type": "ESTIMATED" }, "calendarLimit": "학회 발표 예정은 확인 일정이며 결과 공개의 보장이 아니다. 발표가 미뤄지거나 OS가 빠지면 대기로 남긴다." }, "computation": { "status": "not_run", "method": "원문·레지스트리·공개 발표의 요약을 바탕으로 한 정성적 방향·유의성 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "기록 전에 레지스트리(ClinicalTrials.gov API v2)·PubMed 검색·스폰서 공지·학회 일정·주요 의학 뉴스를 확인했고 영수증과 URL을 eligibility 감사 파일에 남겼다. 모든 언어·학회·기업 공시를 전수 확인하지는 못했다.", "작성 모델의 학습 자료에는 기록 시각 이전의 공개 정보가 들어 있을 수 있다. '알려진 배경'으로 적은 것 밖의 결과를 모른다는 점을 독립적으로 감사하지 못한다. 내부 날짜·해시는 외부 사전등록이 아니다.", "이 기록은 예측 훈련이다. 임상시험은 해당 연구진과 스폰서의 성과이며, 이 기록이 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] }, { "id": "PR-003", "version": 1, "by": "Claude", "added": "2026-10-03", "recordedAt": "2026-10-03T21:10:00+09:00", "informationCutoff": "2026-10-03T21:10:00+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "DESTINY-Breast09에서 퍼투주맙 없이 T-DXd만 쓴 군도 1차 THP보다 무진행생존이 길까", "language": "ko" }, "links": { "pairs": [], "units": [ "U-DB09", "U-DB03", "U-CLEOPATRA", "U-DB11" ], "nct": "NCT04784715", "trial": "B-DB09" }, "target": { "program": "breast", "population": "중앙 확인 HER2 양성 진행성·전이성 유방암, 전이 단계 1차 치료 대상(상세는 등록 기준)", "treatment": "T-DXd + 퍼투주맙 위약(Arm A)", "comparator": "탁산 + 트라스투주맙 + 퍼투주맙(THP, Arm C)", "endpoint": "BICR 평가 무진행생존(RECIST 1.1 진행 또는 모든 원인 사망)", "analysisPopulation": "Arm A와 Arm C의 무작위배정(ITT) 집단", "selection": "기록 시각 뒤 처음 공개되는 Arm A 대 Arm C 사전 계획 PFS 분석의 주 HR과 시험의 유의성 판정; Arm B(T-DXd + 퍼투주맙) 결과로 대체하지 않음", "endpointDefinitionLimit": "Arm A 대 C 비교의 알파 배분·분석 시점·다중성 보정은 공개 자료에서 확인하지 못했다. 대조 전에 발표 자료와 SAP로 확인한다." }, "forecast": { "text": "T-DXd 단독(Arm A) 대 THP(Arm C)의 BICR PFS HR은 1 미만이고, 시험의 사전 유의 경계를 넘을 것으로 예상한다.", "quantity": "BICR progression-free survival hazard ratio, T-DXd + placebo / THP", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": "significant", "uncertainty": "중간; 같은 시험 병용군의 결과가 강한 근거지만 퍼투주맙의 기여와 독성에 따른 조기 중단 효과를 분리할 수 없다.", "basis": [ "같은 시험에서 T-DXd + 퍼투주맙(Arm B)은 THP보다 PFS가 길었다(U-DB09). 단독군 결과로 그대로 옮기지 않는다.", "앞선 치료 뒤 HER2 양성 전이 유방암에서 T-DXd는 T-DM1보다 PFS가 크게 길었다(U-DB03).", "Arm A는 Arm B와 위약으로 눈가림되어 있으며, 기록 시점까지 Arm A 결과의 방향은 공개되지 않았다." ], "counterarguments": [ "THP는 전체생존 이득이 확인된 강한 기준 치료이며(U-CLEOPATRA), 이 시험의 THP군 PFS도 길었다(U-DB09). 이중 HER2 차단을 뺀 단독군이 이를 넘지 못할 수 있다.", "조기 고위험 HER2 양성 유방암의 DESTINY-Breast11에서는 T-DXd 단독군 모집이 독립자료감시위원회 권고로 조기 종료됐다(U-DB11). 상황이 다르지만 단독 요법의 한계를 시사할 수 있다.", "간질성 폐질환 등으로 T-DXd를 일찍 중단하면 PFS 이득이 줄 수 있다." ], "assumptions": [ "처음 공개될 Arm A 대 C 분석이 ITT 원 배정 비교와 BICR 평가를 유지한다.", "병용군의 이득 가운데 상당 부분이 T-DXd 자체에서 온다." ], "changesMind": "Arm A 대 C의 주 HR이 1 이상이거나 사전 경계를 넘지 못하면 해당 부분을 불일치로 기록한다. Arm B 결과나 하위집단으로 바꾸지 않는다.", "nextActionIfSupported": "퍼투주맙의 추가 기여를 Arm A 대 B 비교의 별도 질문으로 정리하고, 독성·치료 기간을 함께 검토한다.", "nextActionIfOpposed": "T-DXd의 이득이 이중 HER2 차단과의 결합에 얼마나 의존하는지에 대한 가정을 복기하고, DESTINY-Breast11 단독군 조기 종료와의 관계를 다음 질문으로 정리한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개(학회 초록 공개·발표·스폰서 공지 중 가장 이른 것)가 recordedAt보다 늦어야 한다. 기록 전에 이미 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력을 보존한다.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "스폰서의 공식 공지와 등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR(T-DXd + 위약 / THP) < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1이거나 반올림으로 방향을 정할 수 없으면 경계값·정밀도 불충분으로 기록한다.", "statisticalRule": "방향·유의성 판정과 임상 이득은 별도다. HR·CI·사건 수·성숙도·다중성·사전 경계를 그대로 기록한다. 방향 일치만으로 생존 이득 확정·완치를 주장하지 않는다.", "unassessableRule": "Arm A 대 C의 유효한 ITT PFS HR이 없거나 평가 방식(BICR)·집단이 다르면 판단 불가 또는 부분 결과로 유지한다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험의 후속 결과를 독립 재현으로 세지 않음.", "significanceRule": "시험이 이 분석에서 사전 정한 유의 경계를 넘었다고 보고하면 'significant', 넘지 못했다고 보고하거나 형식 검정이 아닌 기술적 분석이라고 밝히면 'not_significant'로 본다. 형식 검정 여부나 경계를 확인할 수 없으면 유의성 부분은 판단 불가로 남긴다. 방향과 유의성은 따로 판정하고 따로 기록한다." }, "waiting": { "startedAt": "2026-10-03T21:10:00+09:00", "estimatedPrimaryCompletion": { "date": "2026-11-11", "type": "ESTIMATED" }, "calendarLimit": "등록의 추정 완료일과 스폰서의 예정 시기는 확인 일정이며 공개 보장이 아니다." }, "computation": { "status": "not_run", "method": "원문·레지스트리·공개 발표의 요약을 바탕으로 한 정성적 방향·유의성 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "기록 전에 레지스트리(ClinicalTrials.gov API v2)·PubMed 검색·스폰서 공지·학회 일정·주요 의학 뉴스를 확인했고 영수증과 URL을 eligibility 감사 파일에 남겼다. 모든 언어·학회·기업 공시를 전수 확인하지는 못했다.", "작성 모델의 학습 자료에는 기록 시각 이전의 공개 정보가 들어 있을 수 있다. '알려진 배경'으로 적은 것 밖의 결과를 모른다는 점을 독립적으로 감사하지 못한다. 내부 날짜·해시는 외부 사전등록이 아니다.", "이 기록은 예측 훈련이다. 임상시험은 해당 연구진과 스폰서의 성과이며, 이 기록이 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] }, { "id": "PR-004", "version": 1, "by": "Claude", "added": "2026-10-03", "recordedAt": "2026-10-03T21:10:00+09:00", "informationCutoff": "2026-10-03T21:10:00+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "SERENA-6에서 ESR1 변이 출현 때 카미제스트란트로 바꾸는 전략은 최종 전체생존에서도 유리할까", "language": "ko" }, "links": { "pairs": [ "QP-08", "QP-43" ], "units": [ "U-SERENA6", "U-EMBER3" ], "nct": "NCT04964934", "trial": "B-SERENA6" }, "target": { "program": "breast", "population": "1차 아로마타제 억제제 + CDK4/6 억제제 치료 중 영상 진행 없이 혈중 ESR1 변이가 출현한 HR 양성/HER2 음성 진행성 유방암", "treatment": "카미제스트란트 + 같은 CDK4/6 억제제로 전환", "comparator": "아로마타제 억제제 + CDK4/6 억제제 유지(위약 이중맹검)", "endpoint": "전체생존(무작위배정부터 모든 원인 사망까지)", "analysisPopulation": "시험이 정한 전체 무작위배정 집단", "selection": "기록 시각 뒤 처음 공개되는 사전 계획 최종 OS 분석의 주 HR과 유의성 판정. 최종 전 OS 갱신이 나오면 부분 결과로 기록하고 최종 대조로 쓰지 않는다.", "endpointDefinitionLimit": "최종 OS 분석의 사건 수 기준과 검정력은 규제 자문 자료로만 확인했다. 대조 전에 발표 자료와 SAP로 다시 확인한다." }, "forecast": { "text": "카미제스트란트 전환군 대 유지군의 최종 OS HR은 1 미만이겠지만, 사전 유의 경계는 넘지 못할 것으로 예상한다.", "quantity": "final overall survival hazard ratio, camizestrant switch / AI continuation", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": "not_significant", "uncertainty": "큼; 최종 분석까지 2년 이상 남았고, 진행 후 치료와 교차 투여에 따라 차이가 희석되거나 커질 수 있다.", "basis": [ "전환 전략은 중간 분석에서 PFS를 늘렸다(U-SERENA6). 이후 공개된 최종 PFS2도 전환군에 유리했다.", "최종 PFS2 시점에 함께 공개된 OS는 1 미만 방향이었지만 미성숙하고 유의하지 않았다. 알려진 배경이다.", "규제 자문 자료에 따르면 최종 OS 분석은 높은 검정력으로 설계되지 않았다.", "ESR1 변이 집단에서 경구 SERD의 이득은 반복 관찰되지만 전체 집단 결과는 갈렸다(U-EMBER3)." ], "counterarguments": [ "조기 전환으로 생긴 PFS·PFS2 이득이 누적되면 최종 분석에서 사망 차이가 경계를 넘을 수 있다.", "유지군 환자가 진행 뒤 받는 후속 치료가 약하면 차이가 커질 수 있다.", "혈중 변이로 선별된 집단의 동질성이 높아 효과가 일정하게 유지될 수 있다." ], "assumptions": [ "최종 OS 분석이 계획대로 원 배정 비교로 수행된다.", "유지군의 진행 후 치료에 SERD·ADC 등 유효한 선택지가 포함된다." ], "changesMind": "최종 OS 분석이 사전 경계를 넘었다고 보고되면 유의성 예측은 불일치로 기록한다. HR이 1 이상이면 방향도 불일치로 기록한다.", "nextActionIfSupported": "혈중 변이에 따른 조기 전환이 생존 이득으로 이어지지 않을 수 있다는 점을 QP-08·QP-43 판단 범위와 대조하고, 진행 후 치료의 영향을 다음 질문으로 정리한다.", "nextActionIfOpposed": "PFS·PFS2에서 OS로 이어지는 속도와 진행 후 치료의 희석 효과에 대한 가정을 복기한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개(학회 초록 공개·발표·스폰서 공지 중 가장 이른 것)가 recordedAt보다 늦어야 한다. 기록 전에 이미 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력을 보존한다.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "스폰서의 공식 공지와 등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR(카미제스트란트 전환 / 유지) < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1이거나 반올림으로 방향을 정할 수 없으면 경계값·정밀도 불충분으로 기록한다.", "statisticalRule": "방향·유의성 판정과 임상 이득은 별도다. HR·CI·사건 수·성숙도·다중성·사전 경계를 그대로 기록한다. 방향 일치만으로 생존 이득 확정·완치를 주장하지 않는다.", "unassessableRule": "최종 OS가 아닌 중간 갱신, 다른 집단, 정의가 다른 결과는 판단 불가 또는 부분 결과로 유지한다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험의 후속 결과를 독립 재현으로 세지 않음.", "significanceRule": "시험이 이 분석에서 사전 정한 유의 경계를 넘었다고 보고하면 'significant', 넘지 못했다고 보고하거나 형식 검정이 아닌 기술적 분석이라고 밝히면 'not_significant'로 본다. 형식 검정 여부나 경계를 확인할 수 없으면 유의성 부분은 판단 불가로 남긴다. 방향과 유의성은 따로 판정하고 따로 기록한다." }, "waiting": { "startedAt": "2026-10-03T21:10:00+09:00", "estimatedPrimaryCompletion": { "date": "2025-06-30", "type": "ACTUAL" }, "calendarLimit": "1차 완료일(PFS)은 지났다. OS 최종 분석 시점은 사건 수에 달려 있으며 공개 보장이 아니다." }, "computation": { "status": "not_run", "method": "원문·레지스트리·공개 발표의 요약을 바탕으로 한 정성적 방향·유의성 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "기록 전에 레지스트리(ClinicalTrials.gov API v2)·PubMed 검색·스폰서 공지·학회 일정·주요 의학 뉴스를 확인했고 영수증과 URL을 eligibility 감사 파일에 남겼다. 모든 언어·학회·기업 공시를 전수 확인하지는 못했다.", "작성 모델의 학습 자료에는 기록 시각 이전의 공개 정보가 들어 있을 수 있다. '알려진 배경'으로 적은 것 밖의 결과를 모른다는 점을 독립적으로 감사하지 못한다. 내부 날짜·해시는 외부 사전등록이 아니다.", "이 기록은 예측 훈련이다. 임상시험은 해당 연구진과 스폰서의 성과이며, 이 기록이 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] }, { "id": "PR-005", "version": 1, "by": "Claude", "added": "2026-10-03", "recordedAt": "2026-10-03T21:10:00+09:00", "informationCutoff": "2026-10-03T21:10:00+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "ASCENT-04에서 사시투주맙 고비테칸과 펨브롤리주맙 병용은 최종 전체생존에서도 표준 병용보다 유리할까", "language": "ko" }, "links": { "pairs": [ "QP-33" ], "units": [ "U-ASCENT04", "U-ASCENT", "U-ASCENT03" ], "nct": "NCT05382286", "trial": "B-ASCENT04" }, "target": { "program": "breast", "population": "이전에 진행성 병기 전신치료를 받지 않은 PD-L1 양성 국소진행·전이성 삼중음성 유방암(상세는 등록 기준)", "treatment": "사시투주맙 고비테칸 + 펨브롤리주맙", "comparator": "펨브롤리주맙 + 의사 선택 화학요법", "endpoint": "전체생존(무작위배정부터 모든 원인 사망까지; 등록상 2차 평가변수)", "analysisPopulation": "시험이 정한 전체 무작위배정(ITT) 집단", "selection": "기록 시각 뒤 처음 공개되는 사전 계획 OS 분석(중간 또는 최종) 가운데 형식 검정이 수행된 첫 분석의 주 HR과 유의성 판정", "endpointDefinitionLimit": "OS의 알파 배분·중간 경계와 대조군의 진행 후 교차 투여 허용 범위는 원 프로토콜에서 확인하지 못했다. 대조 전에 확인한다." }, "forecast": { "text": "사시투주맙 병용군 대 표준 병용군의 OS HR은 1 미만이겠지만, 형식 검정이 수행된 첫 OS 분석에서 사전 유의 경계는 넘지 못할 것으로 예상한다.", "quantity": "overall survival hazard ratio, sacituzumab govitecan + pembrolizumab / chemotherapy + pembrolizumab", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": "not_significant", "uncertainty": "큼; 1차 분석 시 OS가 미성숙했고, 대조군의 진행 후 ADC 사용에 따라 차이가 희석될 수 있다.", "basis": [ "중앙 평가 PFS가 개선됐고, 1차 분석 시점의 OS는 미성숙했다(U-ASCENT04).", "앞선 치료 뒤 전이성 삼중음성 유방암에서 사시투주맙은 OS를 늘렸다(U-ASCENT). 1차 병용 맥락으로 효과크기를 옮기지 않는다.", "PD-L1 음성 1차 집단의 ASCENT-03에서도 PFS가 개선됐지만, 원 초록에는 OS 수치가 보고되지 않았다(U-ASCENT03)." ], "counterarguments": [ "2차 이후 사시투주맙의 OS 이득이 컸으므로, 1차에 먼저 쓰는 이득이 생존으로 이어질 수 있다.", "양 군 모두 펨브롤리주맙을 받아 면역치료 효과가 상쇄되므로, 남는 차이가 사시투주맙 자체의 효과로 비교적 깨끗하게 드러날 수 있다.", "대조군의 교차 투여가 제한적이면 차이가 희석되지 않는다." ], "assumptions": [ "처음 형식 검정되는 OS 분석이 ITT 원 배정 비교를 유지한다.", "대조군의 상당수가 진행 뒤 TROP2 ADC 등 유효한 후속 치료를 받는다." ], "changesMind": "형식 검정된 첫 OS 분석이 사전 경계를 넘었다고 보고되면 유의성 예측은 불일치로 기록한다. HR이 1 이상이면 방향도 불일치로 기록한다.", "nextActionIfSupported": "PFS 이득과 OS 사이의 간격을 QP-33 판단 범위와 대조하고, 치료 순서(1차 대 후속 ADC)를 다음 질문으로 정리한다.", "nextActionIfOpposed": "후속 치료의 희석 효과와 1차 사용 이득에 대한 가정을 복기하고, 교차 투여 비율을 확인해 다음 질문으로 정리한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개(학회 초록 공개·발표·스폰서 공지 중 가장 이른 것)가 recordedAt보다 늦어야 한다. 기록 전에 이미 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력을 보존한다.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "스폰서의 공식 공지와 등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR(사시투주맙 + 펨브롤리주맙 / 화학요법 + 펨브롤리주맙) < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1이거나 반올림으로 방향을 정할 수 없으면 경계값·정밀도 불충분으로 기록한다.", "statisticalRule": "방향·유의성 판정과 임상 이득은 별도다. HR·CI·사건 수·성숙도·다중성·사전 경계를 그대로 기록한다. 방향 일치만으로 생존 이득 확정·완치를 주장하지 않는다.", "unassessableRule": "형식 검정이 없는 기술적 갱신만 있으면 부분 결과로 기록하고 대기를 유지한다. PFS·하위집단으로 대체하지 않는다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험의 후속 결과를 독립 재현으로 세지 않음.", "significanceRule": "시험이 이 분석에서 사전 정한 유의 경계를 넘었다고 보고하면 'significant', 넘지 못했다고 보고하거나 형식 검정이 아닌 기술적 분석이라고 밝히면 'not_significant'로 본다. 형식 검정 여부나 경계를 확인할 수 없으면 유의성 부분은 판단 불가로 남긴다. 방향과 유의성은 따로 판정하고 따로 기록한다." }, "waiting": { "startedAt": "2026-10-03T21:10:00+09:00", "estimatedPrimaryCompletion": { "date": "2027-02", "type": "ESTIMATED" }, "calendarLimit": "등록의 추정 완료일은 확인 일정이며 공개 보장이 아니다." }, "computation": { "status": "not_run", "method": "원문·레지스트리·공개 발표의 요약을 바탕으로 한 정성적 방향·유의성 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "기록 전에 레지스트리(ClinicalTrials.gov API v2)·PubMed 검색·스폰서 공지·학회 일정·주요 의학 뉴스를 확인했고 영수증과 URL을 eligibility 감사 파일에 남겼다. 모든 언어·학회·기업 공시를 전수 확인하지는 못했다.", "작성 모델의 학습 자료에는 기록 시각 이전의 공개 정보가 들어 있을 수 있다. '알려진 배경'으로 적은 것 밖의 결과를 모른다는 점을 독립적으로 감사하지 못한다. 내부 날짜·해시는 외부 사전등록이 아니다.", "이 기록은 예측 훈련이다. 임상시험은 해당 연구진과 스폰서의 성과이며, 이 기록이 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] }, { "id": "PR-006", "version": 1, "by": "Claude", "added": "2026-10-03", "recordedAt": "2026-10-03T21:10:00+09:00", "informationCutoff": "2026-10-03T21:10:00+09:00", "status": "awaiting_result", "recordType": "literature_result_forecast", "externalPreregistration": false, "question": { "text": "DESTINY-Breast05에서 수술 뒤 잔존 질환에 쓴 T-DXd는 T-DM1보다 전체생존에서도 유리한 방향일까", "language": "ko" }, "links": { "pairs": [ "QP-32" ], "units": [ "U-DB05", "U-KATHERINE", "U-DB03" ], "nct": "NCT04622319", "trial": "B-DB05" }, "target": { "program": "breast", "population": "수술 전 치료 뒤 침윤성 잔존 질환이 남은 고위험 HER2 양성 조기 유방암(상세는 등록 기준)", "treatment": "트라스투주맙 데룩스테칸(T-DXd)", "comparator": "트라스투주맙 엠탄신(T-DM1)", "endpoint": "전체생존(무작위배정부터 모든 원인 사망까지; 등록상 2차 평가변수)", "analysisPopulation": "시험이 정한 전체 무작위배정(ITT) 집단", "selection": "기록 시각 뒤 처음 공개되는 사전 계획 OS 분석의 주 HR", "endpointDefinitionLimit": "OS 분석의 사건 수 기준·일정·경계는 확인하지 못했다. 대조 전에 발표 자료와 SAP로 확인한다." }, "forecast": { "text": "T-DXd군 대 T-DM1군의 OS HR은 1 미만일 것으로 예상한다. 유의성은 예측하지 않는다.", "quantity": "overall survival hazard ratio, T-DXd / T-DM1", "operator": "<", "threshold": 1, "probability": null, "effectSizeEstimate": null, "significancePrediction": null, "uncertainty": "큼; 사망 사건이 매우 적고, 재발 뒤 T-DM1군이 전이 단계에서 T-DXd를 받으면 차이가 희석된다. 유의성을 예측할 근거가 부족하다.", "basis": [ "무침습질병생존이 T-DXd군에서 크게 개선됐다(U-DB05).", "같은 잔존 질환 맥락에서 T-DM1은 트라스투주맙보다 무침습질병생존과 이후 OS를 개선했다(U-KATHERINE). 재발 감소가 장기적으로 사망 감소로 이어진 선례다.", "앞서 공개된 OS는 사건이 매우 적어 해석할 수 없는 수준이었다. 알려진 배경이다." ], "counterarguments": [ "T-DXd군에서 약물 관련 간질성 폐질환이 더 많았고 사망 사례도 보고됐다(U-DB05). 사건이 적은 OS에서는 치료 관련 사망이 방향을 흔들 수 있다.", "T-DM1은 이미 OS 이득이 확인된 강한 비교 기준이다(U-KATHERINE).", "재발한 T-DM1군 환자가 전이 단계에서 T-DXd를 받으면(U-DB03) 생존 차이가 줄 수 있다." ], "assumptions": [ "처음 공개될 OS 분석이 ITT 원 배정 비교를 유지한다.", "무침습질병생존 차이가 시간이 지나도 유지된다." ], "changesMind": "처음 공개되는 OS 주 HR이 1 이상이면 불일치로 기록한다. 사건 수가 너무 적어 방향을 정할 수 없다고 발표되면 판단 불가로 남긴다.", "nextActionIfSupported": "재발 감소가 사망 감소로 이어지는 속도를 KATHERINE과 비교해 QP-32 판단 범위를 점검한다.", "nextActionIfOpposed": "치료 관련 독성과 재발 후 치료의 영향에 대한 가정을 복기하고 다음 질문으로 정리한다." }, "comparisonPlan": { "prospectivenessGate": "적격 결과 또는 그 방향의 최초 공개(학회 초록 공개·발표·스폰서 공지 중 가장 이른 것)가 recordedAt보다 늦어야 한다. 기록 전에 이미 공개돼 있던 방향을 뒤늦게 발견하면 사전 예측 평가에서 제외하고 이력을 보존한다.", "sourceOrder": [ "시험 연구진의 원 학회 초록/발표", "스폰서의 공식 공지와 등록 레지스트리의 원 결과", "원논문; 앞선 공개 자료와 버전·분모 대조" ], "directionRule": "주 HR(T-DXd / T-DM1) < 1이면 예상 방향과 일치, > 1이면 불일치. 정확히 1이거나 반올림으로 방향을 정할 수 없으면 경계값·정밀도 불충분으로 기록한다.", "statisticalRule": "방향·유의성 판정과 임상 이득은 별도다. HR·CI·사건 수·성숙도·다중성·사전 경계를 그대로 기록한다. 방향 일치만으로 생존 이득 확정·완치를 주장하지 않는다.", "unassessableRule": "유효한 ITT OS HR이 없으면 판단 불가 또는 부분 결과로 유지한다. 무침습질병생존·하위집단으로 대체하지 않는다.", "changesAfterRecording": "원본 v1 보존; 추가 정보·예측 수정은 새 버전, 대조 결과·실패 복기는 별도 날짜 기록. 같은 시험의 후속 결과를 독립 재현으로 세지 않음." }, "waiting": { "startedAt": "2026-10-03T21:10:00+09:00", "estimatedPrimaryCompletion": { "date": "2025-07-02", "type": "ACTUAL" }, "calendarLimit": "1차 완료일(IDFS)은 지났다. OS 분석 시점은 사건 수에 달려 있으며 공개 보장이 아니다." }, "computation": { "status": "not_run", "method": "원문·레지스트리·공개 발표의 요약을 바탕으로 한 정성적 방향·유의성 예측; 환자 경과 모사·새 계산 모델 없음" }, "outcome": null, "comparison": null, "independentBiologicalValidation": false, "clinicalEfficacyClaim": false, "provenanceLimits": [ "기록 전에 레지스트리(ClinicalTrials.gov API v2)·PubMed 검색·스폰서 공지·학회 일정·주요 의학 뉴스를 확인했고 영수증과 URL을 eligibility 감사 파일에 남겼다. 모든 언어·학회·기업 공시를 전수 확인하지는 못했다.", "작성 모델의 학습 자료에는 기록 시각 이전의 공개 정보가 들어 있을 수 있다. '알려진 배경'으로 적은 것 밖의 결과를 모른다는 점을 독립적으로 감사하지 못한다. 내부 날짜·해시는 외부 사전등록이 아니다.", "이 기록은 예측 훈련이다. 임상시험은 해당 연구진과 스폰서의 성과이며, 이 기록이 공개 임상 근거·환자·자체 분석 수를 늘리지 않는다." ] } ], "forecasting": { "judgmentScopes": { "QP-01": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-02": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-03": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-04": "일차 평가변수 개선 미입증 시 가설 채택, 실패 횟수만으로 자동 기각·약제 계열 전체 확대, 편익 미입증과 효과 없음 입증 구분 없는 해석을 보류", "QP-05": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-06": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-07": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-08": "전체 생존·후속 치료 결과·위해 단정과 조직 변이 검출 차이만으로 교체 전략 효과·변이 획득 원인을 설명하는 판단을 보류", "QP-09": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-10": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-11": "순서를 비교한 무작위 연구 부재 하에서 ADC 이어쓰기 결과를 추정하는 판단을 보류", "QP-12": "예측 서버 출력의 자동 검색·도킹/스크리닝 도구 연결 판단을 보류", "QP-13": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-14": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-15": "표적 신호 의존성과 묶은 주장 및 이번 전임상 자료로 임상 사용 순서를 추정하는 판단을 보류", "QP-16": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-17": "모델에서 관찰한 감수성 연관성을 환자 선별 검사로 확정하는 판단을 보류", "QP-18": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-19": "현재 추적에서 보류로 표시되지 않음. 과학적 완성·검증 완료를 의미하지 않음.", "QP-20": "각 연구 내 결론은 유지하되 연구 사이 효과 크기로 치료 우열을 매기는 판단을 보류", "QP-21": "검사 결과에 따라 치료를 바꿨을 때 재발이나 사망이 줄어든다는 판단(치료 변경의 임상적 유용성) 보류", "QP-22": "소수의 투여 결과만으로 약제의 재발 방지 효능이 확정적으로 실패했다는 판단 보류", "QP-23": "반응 및 지속적 질병 제어 인정 외 완치 확정 판단 보류", "QP-24": "검사에 따라 치료를 바꾼 이득을 다른 병기 및 암종으로 확대하는 판단 보류", "QP-25": "해당 자료만으로 개인별 과잉진단 여부나 검진의 이득과 위해를 확정하는 판단 보류", "QP-26": "갑상선염과 암 동반 관찰에 대한 인과 판단 보류", "QP-27": "단일군 반응에 기반하여 다른 치료보다 우월하다는 판단 보류", "QP-28": "작은 탐색 하위군에 따른 효과 크기의 확정이나 재검사 기반 치료 선택 전략의 유용성 판단 보류", "QP-29": "후속 치료나 교차 투여의 영향을 근거로 미확인 생존 이득을 확정하는 판단 보류", "QP-30": "확인된 생존 이득을 완치나 다른 병기·위험 집단의 효과로 확대하는 판단 보류", "QP-31": "수술 전후 병용 및 단독 투여 단계 중 어느 단계가 필요하거나 생략 가능한지에 대한 인과적 기여 판단 보류", "QP-32": "해당 결과만으로 전체 생존 이득이나 모든 잔존암 집단에서의 동일한 이득을 확정하는 판단 보류", "QP-33": "미성숙한 전체 생존 자료에 근거한 생존 개선 및 다른 선별 집단으로의 확대 판단 보류", "QP-34": "미성숙한 전체 생존에 근거한 전체 생존 개선 판단 보류", "QP-35": "시험 사이의 약제 우열, 계열 전체의 지속 효과, 전체 생존 이득에 대한 판단 보류", "QP-36": "시험 사이의 수치 차이로 약제 순위를 정하거나 모든 조기 유방암으로 효과를 확대하는 판단 보류", "QP-37": "시험 사이의 숫자로 최적 기간이나 약제 순위를 정하는 판단 보류", "QP-38": "현재 추적 목록에서 보류로 플래그되지 않음 (과학적 완결이나 확실성을 의미하지 않음)", "QP-39": "현재 추적 목록에서 보류로 플래그되지 않음 (과학적 완결이나 확실성을 의미하지 않음)", "QP-40": "나이와 폐경 상태를 바꾸어 쓰거나 탐색 결과로 개인의 치료 이득을 확정하는 판단 보류", "QP-41": "현재 추적 목록에서 보류로 플래그되지 않음 (과학적 완결이나 확실성을 의미하지 않음)", "QP-42": "수술 전 면역치료 후 수술 뒤 면역치료 생략의 안전성과 비열등성 판단 보류", "QP-43": "변이 선별의 비교 우위·수용체 분해제 순위와 치료 순서 판단 보류", "QP-44": "혈액 미검출에 따른 직장 절제 생략의 안전성과 전체 재발 검출 성능 판단 보류", "QP-45": "핵 내 단백질 기반 환자 선별과 내성 병용치료의 임상 이득 판단 보류", "QP-46": "치료 후 조직검사 기반 치료 선택의 이득과 독립 예측 성능 판단 보류", "QP-47": "소기관 제거 경로 억제에 따른 환자 선별·임상 이득·안전성 판단 보류", "QP-48": "소엽암의 아형별 위험 차이와 조직형 기반 치료 이득 판단 보류", "QP-49": "증식 지표 변화의 확정적 예후 가치와 검사 기반 수술 선택 판단 보류", "QP-50": "점수가 낮은 구간과 전체 환자에서의 면역항암 병용 이득 판단 보류", "QP-51": "대장암 HER2 표적치료의 표준치료 대비 이득과 저발현 환자 반응 판단 보류", "QP-52": "같은 계열 약 사이, 진행성과 조기 사이의 생존 이득 일반화 판단 보류", "QP-53": "하시모토 갑상선염이 갑상선암을 일으킨다는 해석과 암의 진행을 막는다는 해석 모두 보류", "QP-54": "하시모토 갑상선염에서 갑상선암이 생기지 않는 조건의 확정 보류", "QP-55": "갑상선 호르몬 치료가 갑상선암 발생을 줄인다는 판단 보류", "QP-56": "결절 환자의 연관성을 소아 갑상선염 환자 전체의 발생 위험으로 넓히는 해석 보류", "QP-57": "진찰이 정상인 갑상선염 환자에서 정기 초음파가 결과를 개선한다는 판단 보류", "QP-58": "소아·청소년 갑상선염 환자의 갑상선암 위험을 단일 수치로 제시하는 판단 보류", "QP-59": "직장암 선행 치료 뒤 경과 관찰이 즉시 수술과 같은 안전성을 가진다는 판단 보류", "QP-60": "영상·병리 반응에 따른 항암 생략이 표준 항암과 같은 결과를 낸다는 판단 보류", "QP-61": "보조 퍼투주맙의 림프절 음성 환자 이득과 전체 생존 이득 판단 보류", "QP-62": "ERBB2 증폭 위암의 공동증폭(주로 CCNE1)이 표적치료 내성의 원인이라는 판단 보류", "QP-63": "dMMR 결장암에서 수술 전 항암의 이득과 수술 전 면역항암의 비교 우위 판단 보류", "QP-64": "호르몬 수용체 양성 조기 유방암에서 수술 전 면역항암이 재발을 줄인다는 판단 보류", "QP-65": "HER2 양성 조기 유방암에서 화학요법 생략이 가능한 환자를 가려내는 방법 판단 보류", "QP-66": "위암 수술 전후 치료에서 병리 반응 상승이 재발·생존 개선을 뜻한다는 판단 보류", "QP-67": "전이 조직의 ESR1 변이 양상이 기관과 검사법이 달라도 성립한다는 판단 보류", "QP-68": "위암에서 수술 뒤 면역항암제가 도움이 되는 환자군이 있다는 판단 보류", "QP-69": "수술 뒤 혈액 종양 DNA 검사 결과에 따른 치료가 재발·생존을 개선한다는 판단 보류", "QP-70": "다른 아형·다른 면역치료로 결과를 이식하는 해석, 동등성 및 수치상 하위군 이득의 해석 보류", "QP-71": "관찰 비교로 리보시클립의 우월성을 확정하거나 시간·미래 처방 선택이 함께 해결됐다고 보는 해석 보류", "QP-72": "pN2-3에서 낮은 점수에 따른 항암 생략 또는 관찰된 생존 연관의 인과효과 해석 보류", "QP-73": "서로 다른 복구 조건을 사람의 공통 병용 치료로 이식하는 해석 보류", "QP-74": "두 BRCA 결핍군에 공통 FANCM 억제 또는 환자군 예측을 제안하는 해석 보류", "QP-75": "모형으로 정의한 감수성·예후 연관을 실제 치료 반응 예측 정확도로 읽는 해석 보류", "QP-76": "혼합 코호트의 위해 비율을 개인별 위험·치료 차수 간 차이·누적 투여량의 인과효과로 해석하는 범위 보류", "QP-77": "특정 항체의 점상 염색 연구를 전체 진단 성능·개인 분자/유전성 판정·치료 반응으로 일반화하는 해석 보류", "QP-78": "확대 관찰 코호트의 생존 연관을 독립 재현·개인별 치료 인과 이득·생략 안전성으로 해석하는 범위 보류", "QP-79": "전체 발현/활성 감소의 세포 효과를 엑손 특이 치료·환자 내성 극복·완치로 해석하는 범위 보류", "QP-80": "갑상선 수질암에서 반데타닙과 카보잔티닙의 우열 및 전체 생존 이득 판단 보류", "QP-81": "저위험 유두암 관찰 결과를 암 진단이 없는 사람·소아·더 큰 종양·평생 안전성으로 넓히는 판단 보류", "QP-82": "선택적 RET 억제제 두 약의 우열 판단 보류", "QP-83": "KRAS G12C 대장암 병용요법의 전체 생존 이득, 저용량 효과, 약제 간 우열 판단 보류", "QP-84": "불응성 대장암 후기 치료의 약제 간 순서와 장기 생존·완치 해석 보류", "QP-85": "3기 결장암 보조 항암 기간을 요법·위험군에 따라 줄이는 판단 보류", "QP-86": "BRAF V600E 대장암 일차 치료의 전체 생존 이득 크기와 항암 병용의 기여 판단 보류", "QP-87": "3기 dMMR 결장암 보조 면역항암의 전체 생존 이득과 다른 전략과의 우열 판단 보류", "QP-102": "단일군 장기 생존을 수술 생략의 안전성·비교 생존 이득·완치로 확대하는 해석 보류", "QP-103": "초기 미생물 병용의 관찰 반응을 제제 단독 기여·사람 내성 극복·비교 이득·완치로 확대하는 해석 보류", "QP-104": "계산 잠재 변수를 생물학적 실측·독립 개인 예측·기준모형 대비 우위·치료 이득으로 확대하는 해석 보류", "QP-105": "실패한 뇌전이 병용에서 경로 전체의 무효·뇌척수액 기반 치료 변경 이득으로 확대하는 해석 보류", "QP-106": "국소 제어의 비열등성을 생존 동등·우월성·조사 생략·장기 위해 부재로 확대하는 해석 보류", "QP-107": "단일군 장기 경과를 수술 전 치료의 독립 기여·비교 이득·완치로 확대하는 해석 보류", "QP-108": "PI3K 변이 대장암 아스피린의 전체 생존 이득과 변이 없는 환자·이차 변이군으로의 확대 판단 보류", "QP-109": "운동 프로그램 이득의 전체 생존 확정, 운동량 기준, 직장암·전이암·다른 암 확대 판단 보류", "QP-110": "pMMR 전이 대장암 면역항암 병용의 이득 판단 보류", "QP-111": "렌바티닙 저용량 시작 전략의 이득 판단 보류", "QP-112": "갑상선암 다중 표적 억제제의 시험 간 순위 판단 보류", "QP-113": "기저 폐 소견의 관찰 연관성을 개인 위험·치료 배제나 감시 전략의 이득으로 확대하는 해석 보류", "QP-114": "호산구의 예후 연관성을 차등 치료 선택 검증·혈구 증가 개입의 사람 재발 예방으로 확대하는 해석 보류", "QP-115": "시험관 구성 점수를 사람의 치료 성공확률·영상 반응·치료 축소 안전성으로 확대하는 해석 보류", "QP-116": "구획별 단일군 신호를 한 반응률·약제 우열·임상 이득·완치로 합치는 해석 보류", "QP-117": "완전반응과 비수술 관리를 선택한 집단의 관찰 비교로 기록한다. 생존 차이를 뚜렷하게 찾지 못한 결과는 동등성이나 비열등성의 입증이 아니다. 반응 확인과 치료 시점·선택·추적 차이를 보존하며, 유지 치료나 수술을 생략하는 전략의 안전성과 완치 확대는 보류한다.", "QP-118": "지방 이용과 세포 사멸 회피를 잇는 기전 가설로 기록한다. 환자 조직의 발현과 실험 모델의 경로 조작을 사람의 전이 치료 효과로 확대하지 않는다. 표적 특이성·구제 실험·노출·위해를 원 방법에서 확인하기 전 약제나 임상 효능의 순위를 정하는 판단은 보류한다.", "QP-119": "잔존 병변을 가진 환자에서의 분류 변화와 예후 연관성으로 기록한다. 생검과 수술 검체의 차이를 치료가 일으킨 생물학적 변화로 단정하지 않고, 선택된 재판독·표본 구성·판독 변동을 함께 살핀다. 재검사에 따라 약제를 정하는 전략의 이득이나 전이암 결과의 이식은 보류한다.", "QP-122": "RAS 야생형 전이성 대장암 전체에서 일차 항EGFR 항체의 생존 우위 판단 보류", "QP-123": "전이성 대장암 강화·보조 항암에서 무병 생존·반응 지표를 생존 이득으로 읽는 판단 보류", "QP-124": "방사성요오드 불응 BRAF 변이 분화 갑상선암에서 MEK 억제제 추가 이득 판단 보류", "QP-130": "병리반응 개선을 생존 이득·동등성 또는 위해 감소로 확대하는 판단 보류", "QP-131": "예후 연관성을 검사 기반 치료·수술 선택의 이득으로 바꾸는 판단 보류", "QP-132": "반복 검사 음성에 따른 치료 축소·중단의 안전성과 완치 판단 보류", "QP-133": "합성 반응 지표에 따른 추가 면역치료 이득·수술 생략 판단 보류", "QP-134": "허투별 비무작위 군 비교를 통한 약제 우열 판단 보류" }, "readouts": { "asOf": "2026-10-30", "rows": [ { "key": "C-OPRA", "nct": "NCT02008656", "acronym": null, "title": "Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2026-11", "daysToPrimaryCompletion": 2, "lastUpdate": "2026-08-24", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT02008656", "unit": "U-OPRA", "program": "colorectal", "result": "descriptive", "pairs": [ "QP-59" ], "forecasts": [] }, { "key": "C-DOSTrectal", "nct": "NCT04165772", "acronym": null, "title": "Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors", "status": "RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2026-11-30", "daysToPrimaryCompletion": 31, "lastUpdate": "2026-10-23", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT04165772", "unit": "U-DOSTrectal", "program": "colorectal", "result": "positive", "pairs": [ "QP-23", "QP-59" ], "forecasts": [] }, { "key": "G-DRAGONIV", "nct": "NCT04208347", "acronym": null, "title": "Perioperative Treatment of Combined SOX With Apatinib and Camrelizumab for Oesophagogastric Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2026-12", "daysToPrimaryCompletion": 32, "lastUpdate": "2026-01-23", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT04208347", "unit": "U-DRAGONIV", "program": "gastric", "result": "positive", "pairs": [ "QP-31" ], "forecasts": [ "PR-001" ] }, { "key": "G-TOPGEAR", "nct": "NCT01924819", "acronym": "TOPGEAR", "title": "Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2026-12-31", "daysToPrimaryCompletion": 62, "lastUpdate": "2025-03-04", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT01924819", "unit": "U-TOPGEAR", "program": "gastric", "result": "negative", "pairs": [ "QP-20" ], "forecasts": [] }, { "key": "B-HER2CR", "nct": "NCT06663787", "acronym": "HER2 CR", "title": "Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Patients Who Achieved Durable Response to Anti-HER2 Treatment", "status": "ACTIVE_NOT_RECRUITING", "phases": [], "primaryCompletion": "2026-12-31", "daysToPrimaryCompletion": 62, "lastUpdate": "2026-05-13", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT06663787", "unit": "U-HER2CR26", "program": "breast", "result": "descriptive", "pairs": [ "QP-132" ], "forecasts": [] }, { "key": "B-ASCENT04", "nct": "NCT05382286", "acronym": "ASCENT-04", "title": "Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2027-02", "daysToPrimaryCompletion": 94, "lastUpdate": "2025-09-18", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT05382286", "unit": "U-ASCENT04", "program": "breast", "result": "positive", "pairs": [ "QP-33" ], "forecasts": [ "PR-005" ] }, { "key": "X-DPT02", "nct": "NCT04482309", "acronym": "DPT02", "title": "A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2027-03-23", "daysToPrimaryCompletion": 144, "lastUpdate": "2026-07-10", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT04482309", "unit": "U-DPT02", "program": "expansion", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-ReDiscover", "nct": "NCT05216432", "acronym": null, "title": "First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer", "status": "RECRUITING", "phases": [ "PHASE1" ], "primaryCompletion": "2027-04-30", "daysToPrimaryCompletion": 182, "lastUpdate": "2025-09-22", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT05216432", "unit": "U-RLY2608", "program": "breast", "result": "descriptive", "pairs": [], "forecasts": [] }, { "key": "B-DB09", "nct": "NCT04784715", "acronym": null, "title": "Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2027-05-03", "daysToPrimaryCompletion": 185, "lastUpdate": "2026-10-22", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT04784715", "unit": "U-DB09", "program": "breast", "result": "positive", "pairs": [], "forecasts": [ "PR-003" ] }, { "key": "G-DANTE", "nct": "NCT03421288", "acronym": "DANTE", "title": "Study of Atezolizumab + FLOT vs. FLOT Alone in Patients With GC/GEJ and High Immune Responsiveness", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2027-05-31", "daysToPrimaryCompletion": 213, "lastUpdate": "2025-07-25", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT03421288", "unit": "U-DANTE", "program": "gastric", "result": "descriptive", "pairs": [ "QP-66" ], "forecasts": [] }, { "key": "B-ASCENT03", "nct": "NCT05382299", "acronym": "ASCENT-03", "title": "Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2028-07", "daysToPrimaryCompletion": 610, "lastUpdate": "2026-04-06", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT05382299", "unit": "U-ASCENT03", "program": "breast", "result": "positive", "pairs": [ "QP-33" ], "forecasts": [] }, { "key": "B-NATALEE", "nct": "NCT03701334", "acronym": "NATALEE", "title": "A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2030-05-29", "daysToPrimaryCompletion": 1307, "lastUpdate": "2026-10-09", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT03701334", "unit": "U-NATALEE", "program": "breast", "result": "positive", "pairs": [ "QP-14", "QP-52" ], "forecasts": [ "PR-002" ] }, { "key": "B-KN756", "nct": "NCT03725059", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2031-01-24", "daysToPrimaryCompletion": 1547, "lastUpdate": "2025-07-11", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT03725059", "unit": "U-KN756", "program": "breast", "result": "mixed", "pairs": [ "QP-64" ], "forecasts": [] }, { "key": "T-ION", "nct": "NCT01398085", "acronym": "IoN", "title": "IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2031-03", "daysToPrimaryCompletion": 1583, "lastUpdate": "2026-05-07", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT01398085", "unit": "U-T-IoN", "program": "thyroid", "result": "positive", "pairs": [ "QP-91" ], "forecasts": [] }, { "key": "C-NICHE2", "nct": "NCT03026140", "acronym": "NICHE", "title": "Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer", "status": "RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2032-03-01", "daysToPrimaryCompletion": 1949, "lastUpdate": "2026-09-30", "hasResults": false, "stage": "upcoming", "url": "https://clinicaltrials.gov/study/NCT03026140", "unit": "U-NICHE2", "program": "colorectal", "result": "positive", "pairs": [ "QP-23", "QP-63", "QP-87", "QP-121" ], "forecasts": [] }, { "key": "B-TRAIN2", "nct": "NCT01996267", "acronym": "TRAIN-2", "title": "Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2018-12", "daysToPrimaryCompletion": -2890, "lastUpdate": "2024-03-29", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT01996267", "unit": "U-TRAIN2", "program": "breast", "result": "negative", "pairs": [ "QP-36", "QP-37" ], "forecasts": [] }, { "key": "T-ESTIMABL2", "nct": "NCT01837745", "acronym": "ESTIMABL2", "title": "Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2022-04-01", "daysToPrimaryCompletion": -1673, "lastUpdate": "2023-05-17", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT01837745", "unit": "U-T-ESTIMABL2", "program": "thyroid", "result": "positive", "pairs": [ "QP-91" ], "forecasts": [] }, { "key": "B-DB08", "nct": "NCT04556773", "acronym": "DB-08", "title": "A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1" ], "primaryCompletion": "2023-08-16", "daysToPrimaryCompletion": -1171, "lastUpdate": "2026-08-03", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04556773", "unit": "U-DB08", "program": "breast", "result": "descriptive", "pairs": [], "forecasts": [] }, { "key": "B-PHERGain", "nct": "NCT03161353", "acronym": "PHERGain", "title": "Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2023-11-01", "daysToPrimaryCompletion": -1094, "lastUpdate": "2025-04-23", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT03161353", "unit": "U-PHERGain", "program": "breast", "result": "positive", "pairs": [ 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"unit": "U-CA2098M4", "program": "colorectal", "result": "mixed", "pairs": [ "QP-133" ], "forecasts": [] }, { "key": "G-MATTERHORN", "nct": "NCT04592913", "acronym": null, "title": "Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-12-20", "daysToPrimaryCompletion": -679, "lastUpdate": "2025-12-24", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04592913", "unit": "U-MATTERHORN", "program": "gastric", "result": "positive", "pairs": [ "QP-31", "QP-42", "QP-66" ], "forecasts": [] }, { "key": "B-SERENA6", "nct": "NCT04964934", "acronym": "SERENA-6", "title": "Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-06-30", "daysToPrimaryCompletion": -487, "lastUpdate": "2026-09-23", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04964934", "unit": "U-SERENA6", "program": "breast", "result": "positive", "pairs": [ "QP-08", "QP-43" ], "forecasts": [ "PR-004" ] }, { "key": "B-DB05", "nct": "NCT04622319", "acronym": null, "title": "A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-07-02", "daysToPrimaryCompletion": -485, "lastUpdate": "2026-05-15", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04622319", "unit": "U-DB05", "program": "breast", "result": "positive", "pairs": [ "QP-32" ], "forecasts": [ "PR-006" ] }, { "key": "C-AkkMSSCRC26", "nct": "NCT06865521", "acronym": null, "title": "Akkermansia Probiotics Plus 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"url": "https://clinicaltrials.gov/study/NCT05306340", "unit": "U-evERA", "program": "breast", "result": "positive", "pairs": [ "QP-43" ], "forecasts": [] }, { "key": "B-TROPIONB02", "nct": "NCT05374512", "acronym": null, "title": "A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-08-25", "daysToPrimaryCompletion": -431, "lastUpdate": "2026-05-15", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT05374512", "unit": "U-TROPIONB02", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-NEONIPIGA", "nct": "NCT04006262", "acronym": "NEONIPIGA", "title": "Pre-operative Nivolumab and Ipilimumab, Followed by Post-operative Nivolumab, for MSI/dMMR Oeso-gastric Adenocarcinoma.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2025-10", "daysToPrimaryCompletion": -394, "lastUpdate": "2025-06-15", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04006262", "unit": "U-NEONIPIGA", "program": "gastric", "result": "descriptive", "pairs": [ "QP-102" ], "forecasts": [] }, { "key": "C-KRYSTAL1", "nct": "NCT03785249", "acronym": null, "title": "Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1", "PHASE2" ], "primaryCompletion": "2026-06-23", "daysToPrimaryCompletion": -129, "lastUpdate": "2026-07-29", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT03785249", "unit": "U-KRYSTAL1CRC", "program": "colorectal", "result": "positive", "pairs": [ "QP-83" ], "forecasts": [] }, { "key": "G-HERIZON", "nct": "NCT05152147", "acronym": "HERIZON-GEA-01", "title": "A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2026-07-15", "daysToPrimaryCompletion": -107, "lastUpdate": "2026-10-20", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT05152147", "unit": "U-HERIZON", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-DG04", "nct": "NCT04704934", "acronym": null, "title": "Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2026-08-31", "daysToPrimaryCompletion": -60, "lastUpdate": "2026-05-27", "hasResults": false, "stage": "past-active", "url": "https://clinicaltrials.gov/study/NCT04704934", "unit": "U-DG04", "program": "gastric", "result": "positive", "pairs": [ "QP-03", "QP-06" ], "forecasts": [] }, { "key": "B-ShortHER", "nct": "NCT00629278", "acronym": null, "title": "Combination Chemotherapy and Trastuzumab in Treating Women With Stage I, Stage II, or Stage III HER2-Positive Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2010-12", "daysToPrimaryCompletion": -5812, "lastUpdate": "2013-08-07", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00629278", "unit": "U-ShortHER", "program": "breast", "result": "negative", "pairs": [ "QP-37" ], "forecasts": [] }, { "key": "T-HILO", "nct": "NCT00415233", "acronym": "HiLo", "title": "High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2011-06", "daysToPrimaryCompletion": -5630, "lastUpdate": "2023-12-19", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00415233", "unit": "U-T-HiLo", "program": "thyroid", "result": "positive", "pairs": [ "QP-91" ], "forecasts": [] }, { "key": "B-PERSEPHONE", "nct": "NCT00712140", "acronym": null, "title": "Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2011-10", "daysToPrimaryCompletion": -5508, "lastUpdate": "2011-09-02", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00712140", "unit": "U-PERSEPHONE", "program": "breast", "result": "positive", "pairs": [ "QP-37" ], "forecasts": [] }, { "key": "C-FIRE3", "nct": "NCT00433927", "acronym": null, "title": "5-FU, Folinic Acid and Irinotecan (FOLFIRI) Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment Colorectal Cancer (CRC)", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2014-04", "daysToPrimaryCompletion": -4595, "lastUpdate": "2014-03-14", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00433927", "unit": "U-FIRE3", "program": "colorectal", "result": "mixed", "pairs": [ "QP-122" ], "forecasts": [] }, { "key": "B-ASTRRA", "nct": "NCT00912548", "acronym": "ASTRRA", "title": "Evaluating the Role of the Addition of Ovarian Function Suppression (OFS) to Tamoxifen in Young Women", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2015-12", "daysToPrimaryCompletion": -3986, "lastUpdate": "2009-06-16", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00912548", "unit": "U-ASTRRA", "program": "breast", "result": "positive", "pairs": [ "QP-14" ], "forecasts": [] }, { "key": "G-EXPEL", "nct": "NCT02140034", "acronym": "EPL", "title": "Extensive Peritoneal Lavage After Curative Gastrectomy for Gastric Cancer: A Randomised Controlled Trial", "status": "UNKNOWN", "phases": [ "NA" ], "primaryCompletion": "2016-05", "daysToPrimaryCompletion": -3834, "lastUpdate": "2014-05-16", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT02140034", "unit": "U-EXPEL", "program": "gastric", "result": "negative", "pairs": [], "forecasts": [] }, { "key": "C-FOxTROT", "nct": "NCT00647530", "acronym": "FOxTROT", "title": "Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery", "status": "UNKNOWN", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2016-12-23", "daysToPrimaryCompletion": -3598, "lastUpdate": "2019-05-17", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00647530", "unit": "U-FOxTROT", "program": "colorectal", "result": "positive", "pairs": [ "QP-63" ], "forecasts": [] }, { "key": "C-TRIBE2", "nct": "NCT02339116", "acronym": "TRIBE2", "title": "Folfoxiri Plus Bev Followed by Reintroduction of Folfoxiri Plus Bev 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"title": "Phase III Study to Compare Perioperative Chemotherapy of Oxaliplatin Combined With S-1(SOX) Versus SOX or Oxaliplatin With Capecitabine (XELOX) as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma With D2 Dissection", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2019-07", "daysToPrimaryCompletion": -2678, "lastUpdate": "2019-09-17", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT01534546", "unit": "U-RESOLVE", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-ctDNAYuan23", "nct": "NCT02887612", "acronym": null, "title": "ctDNA for Prediction of Relapse in Gastric Cancer", "status": "UNKNOWN", "phases": [], "primaryCompletion": "2019-12", "daysToPrimaryCompletion": -2525, "lastUpdate": "2019-02-26", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT02887612", "unit": "U-ctDNAYuan23", "program": "gastric", "result": "descriptive", "pairs": [ "QP-21", "QP-24" ], "forecasts": [] }, { "key": "G-ARTIST2", "nct": "NCT01761461", "acronym": "ARTIST-II", "title": "Phase III Randomized Trial of Adjuvant Chemotherapy With S-1 vs S-1/Oxaliplatin ± Radiotherapy for Completely Resected Gastric Adenocarcinoma : The ARTIST II Trial", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2020-12", "daysToPrimaryCompletion": -2159, "lastUpdate": "2020-03-25", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT01761461", "unit": "U-ARTIST2", "program": "gastric", "result": "mixed", "pairs": [ "QP-20" ], "forecasts": [] }, { "key": "B-NabDDHR", "nct": "NCT04182568", "acronym": null, "title": "Nab-paclitaxel Compared With Docetaxel Followed by Anthracyclines and Cyclophosphamide in the Neoadjuvant Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE4" ], "primaryCompletion": "2021-08-21", "daysToPrimaryCompletion": -1896, "lastUpdate": "2019-12-02", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT04182568", "unit": "U-NabDDHR26", "program": "breast", "result": "mixed", "pairs": [ "QP-130" ], "forecasts": [] }, { "key": "B-cTRAKTN", "nct": "NCT03145961", "acronym": "c-TRAK-TN", "title": "A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients", "status": "UNKNOWN", "phases": [ "PHASE2" ], "primaryCompletion": "2021-09-30", "daysToPrimaryCompletion": -1856, "lastUpdate": "2022-02-24", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT03145961", "unit": "U-cTRAKTN", "program": "breast", "result": "mixed", "pairs": [ "QP-22", "QP-24", "QP-69" ], "forecasts": [] }, { "key": "G-ARMANI", "nct": "NCT02934464", "acronym": "ARMANI", "title": "Assessment of Ramucirumab Plus Paclitaxel as Switch MANteInance Versus Continuation of First-line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2021-12", "daysToPrimaryCompletion": -1794, "lastUpdate": "2021-09-13", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT02934464", "unit": "U-ARMANI", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-INTEGRATE2A", "nct": "NCT02773524", "acronym": "INTEGRATEIIa", "title": "A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2022-01", "daysToPrimaryCompletion": -1763, "lastUpdate": "2022-01-13", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT02773524", "unit": "U-INTEGRATE2A", "program": "gastric", "result": "positive", "pairs": [ "QP-39" ], "forecasts": [] }, { "key": "B-PHILA", "nct": "NCT03863223", "acronym": null, "title": "A Study of Pyrotinib in Combination With Trastuzumab and Docetaxel in Patients With HER2 Metastatic Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2022-12-30", "daysToPrimaryCompletion": -1400, "lastUpdate": "2022-11-23", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT03863223", "unit": "U-PHILA", "program": "breast", "result": "positive", "pairs": [ "QP-90" ], "forecasts": [] }, { "key": "C-CIRCULATE-AIO", "nct": "NCT04089631", "acronym": "CIRCULATE", "title": "Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2023-06", "daysToPrimaryCompletion": -1247, "lastUpdate": "2020-08-06", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT04089631", "unit": "U-CIRCULATE-AIO", "program": "colorectal", "result": "negative", "pairs": [], "forecasts": [] }, { "key": "G-ESOPEC", "nct": "NCT02509286", "acronym": "ESOPEC", "title": "Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": "2024-05-01", "daysToPrimaryCompletion": -912, "lastUpdate": "2024-05-08", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT02509286", "unit": "U-ESOPEC", "program": "gastric", "result": "positive", "pairs": [ "QP-89" ], "forecasts": [] }, { "key": "B-ATLAS", "nct": "NCT00003016", "acronym": null, "title": "Prolonged Tamoxifen Compared With Shorter Tamoxifen in Treating Patients Who Have Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": null, "daysToPrimaryCompletion": null, "lastUpdate": "2009-02-09", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00003016", "unit": "U-ATLAS", "program": "breast", "result": "positive", "pairs": [ "QP-14" ], "forecasts": [] }, { "key": "T-ESTIMABL1", "nct": "NCT00435851", "acronym": "Estimabl", "title": "Medico-Economic Comparison of Four Strategies of Radioiodine Ablation in Thyroid Carcinoma Patients", "status": "UNKNOWN", "phases": [ "PHASE3" ], "primaryCompletion": null, "daysToPrimaryCompletion": null, "lastUpdate": "2007-02-19", "hasResults": false, "stage": "unknown", "url": "https://clinicaltrials.gov/study/NCT00435851", "unit": "U-T-ESTIMABL1", "program": "thyroid", "result": "positive", "pairs": [ "QP-91" ], "forecasts": [] }, { "key": "C-MOSAIC", "nct": "NCT00275210", "acronym": null, "title": "MOSAIC - Multicenter International Study of Oxaliplatin/ 5FU-LV in the Adjuvant Treatment of Colon Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2003-04", "daysToPrimaryCompletion": -8613, "lastUpdate": "2009-04-20", "hasResults": false, "stage": "past-closed", "url": "https://clinicaltrials.gov/study/NCT00275210", "unit": "U-MOSAIC", "program": "colorectal", "result": "positive", 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"C-CALGB80405", "nct": "NCT00265850", "acronym": null, "title": "Cetuximab and/or Bevacizumab Combined With Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2015-02", "daysToPrimaryCompletion": -4289, "lastUpdate": "2026-08-07", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT00265850", "unit": "U-CALGB80405", "program": "colorectal", "result": "negative", "pairs": [ "QP-122" ], "forecasts": [] }, { "key": "G-GATSBY", "nct": "NCT01641939", "acronym": null, "title": "A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer", "status": "TERMINATED", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2015-06-30", "daysToPrimaryCompletion": -4140, "lastUpdate": "2017-05-12", "hasResults": true, "stage": "posted", "url": 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"https://clinicaltrials.gov/study/NCT02000622", "unit": "U-OlympiAD", "program": "breast", "result": "mixed", "pairs": [], "forecasts": [] }, { "key": "B-APHINITY", "nct": "NCT01358877", "acronym": "APHINITY", "title": "A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2016-12-19", "daysToPrimaryCompletion": -3602, "lastUpdate": "2025-11-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01358877", "unit": "U-APHINITY", "program": "breast", "result": "mixed", "pairs": [ "QP-61" ], "forecasts": [] }, { "key": "G-RAINFALL", "nct": "NCT02314117", "acronym": "RAINFALL", "title": "A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-01-17", "daysToPrimaryCompletion": -3573, "lastUpdate": "2021-08-26", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02314117", "unit": "U-RAINFALL", "program": "gastric", "result": "mixed", "pairs": [], "forecasts": [] }, { "key": "B-MONARCH2", "nct": "NCT02107703", "acronym": "MONARCH 2", "title": "A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2017-02-14", "daysToPrimaryCompletion": -3545, "lastUpdate": "2026-10-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02107703", "unit": "U-MONARCH2", "program": "breast", "result": "positive", "pairs": [ "QP-88" ], "forecasts": [] }, { "key": "B-SALSA", "nct": "NCT00295620", "acronym": "SALSA", "title": "Secondary Adjuvant Long Term Study With Arimidex", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-06-30", "daysToPrimaryCompletion": -3409, "lastUpdate": "2019-10-02", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT00295620", "unit": "U-SALSA", "program": "breast", "result": "negative", "pairs": [ "QP-14" ], "forecasts": [] }, { "key": "B-ML7", "nct": "NCT02278120", "acronym": "MONALEESA-7", "title": "Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-08-21", "daysToPrimaryCompletion": -3357, "lastUpdate": "2024-03-12", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02278120", "unit": "U-ML7", "program": "breast", "result": "positive", "pairs": [ "QP-88" ], "forecasts": [] }, { "key": "B-EMBRACA", "nct": "NCT01945775", "acronym": "EMBRACA", "title": "A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-09-15", "daysToPrimaryCompletion": -3332, "lastUpdate": "2022-01-20", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01945775", "unit": "U-EMBRACA", "program": "breast", "result": "mixed", "pairs": [ "QP-29" ], "forecasts": [] }, { "key": "G-KN061", "nct": "NCT02370498", "acronym": null, "title": "A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-10-26", "daysToPrimaryCompletion": -3291, "lastUpdate": "2022-06-06", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02370498", "unit": "U-KN061", "program": "gastric", "result": "negative", "pairs": [ "QP-03" ], "forecasts": [] }, { "key": "B-ML3", "nct": "NCT02422615", "acronym": "MONALEESA-3", "title": "Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2017-11-03", "daysToPrimaryCompletion": -3283, "lastUpdate": "2023-11-30", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02422615", "unit": "U-ML3", "program": "breast", "result": "positive", "pairs": [ "QP-88" ], "forecasts": [] }, { "key": "B-TAILORx", "nct": "NCT00310180", "acronym": "TAILORx", "title": "Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2018-03-02", "daysToPrimaryCompletion": -3164, "lastUpdate": "2026-10-01", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT00310180", "unit": "U-TAILORx", "program": "breast", "result": "mixed", "pairs": [ "QP-40" ], "forecasts": [] }, { "key": "G-TAGS", "nct": "NCT02500043", "acronym": null, "title": "Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2018-04-30", "daysToPrimaryCompletion": -3105, "lastUpdate": "2024-09-03", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02500043", "unit": "U-TAGS", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "T-ASTRA", "nct": "NCT01843062", "acronym": "ASTRA", "title": "Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer", "status": "TERMINATED", "phases": [ "PHASE3" ], "primaryCompletion": "2018-05-18", "daysToPrimaryCompletion": -3087, "lastUpdate": "2019-08-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01843062", "unit": "U-T-ASTRA", "program": "thyroid", "result": "negative", "pairs": [], "forecasts": [] }, { "key": "B-SOLAR1", "nct": "NCT02437318", "acronym": "SOLAR-1", "title": "Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2018-06-12", "daysToPrimaryCompletion": -3062, "lastUpdate": "2025-02-13", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02437318", "unit": "U-SOLAR1", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-KATHERINE", "nct": "NCT01772472", "acronym": null, "title": "A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2018-07-25", "daysToPrimaryCompletion": -3019, "lastUpdate": "2025-07-22", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01772472", "unit": "U-KATHERINE", "program": "breast", "result": "positive", "pairs": [ "QP-20", "QP-28", "QP-32", "QP-34", "QP-36", "QP-61" ], "forecasts": [] }, { "key": "B-NALA", "nct": "NCT01808573", "acronym": "NALA", "title": "A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2018-09-28", "daysToPrimaryCompletion": -2954, "lastUpdate": "2021-06-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01808573", "unit": "U-NALA", "program": "breast", "result": "mixed", "pairs": [ "QP-90" ], "forecasts": [] }, { "key": "G-PRODIGY", "nct": "NCT01515748", "acronym": "PRODIGY", "title": "Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-01-21", "daysToPrimaryCompletion": -2839, "lastUpdate": "2023-12-13", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01515748", "unit": "U-PRODIGY", "program": "gastric", "result": "positive", "pairs": [ "QP-20" ], "forecasts": [] }, { "key": "C-BEACON", "nct": "NCT02928224", "acronym": "BEACON CRC", "title": "Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-02-11", "daysToPrimaryCompletion": -2818, "lastUpdate": "2023-12-21", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02928224", "unit": "U-BEACON", "program": "colorectal", "result": "positive", "pairs": [ "QP-86" ], "forecasts": [] }, { "key": "G-KN062", "nct": "NCT02494583", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-03-26", "daysToPrimaryCompletion": -2775, "lastUpdate": "2023-04-13", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02494583", "unit": "U-KN062", "program": "gastric", "result": "mixed", "pairs": [], "forecasts": [] }, { "key": "C-DCRC01", "nct": "NCT03384940", "acronym": null, "title": "DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2019-08-09", "daysToPrimaryCompletion": -2639, "lastUpdate": "2021-10-18", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03384940", "unit": "U-DCRC01", "program": "colorectal", "result": "mixed", "pairs": [ "QP-51" ], "forecasts": [] }, { "key": "B-ATEMPT", "nct": "NCT01853748", "acronym": null, "title": "T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2019-08-26", "daysToPrimaryCompletion": -2622, "lastUpdate": "2026-02-19", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01853748", "unit": "U-ATEMPT", "program": "breast", "result": "mixed", "pairs": [ "QP-37", "QP-60" ], "forecasts": [] }, { "key": "B-HER2CLIMB", "nct": "NCT02614794", "acronym": "HER2CLIMB", "title": "A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2019-09-04", "daysToPrimaryCompletion": -2613, "lastUpdate": "2023-08-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02614794", "unit": "U-HER2CLIMB", "program": "breast", "result": "positive", "pairs": [ "QP-90" ], "forecasts": [] }, { "key": "G-JAVG100", "nct": "NCT02625610", "acronym": null, "title": "Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-09-13", "daysToPrimaryCompletion": -2604, "lastUpdate": "2022-06-09", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02625610", "unit": "U-JAVG100", "program": "gastric", "result": "negative", "pairs": [ "QP-29" ], "forecasts": [] }, { "key": "G-DG01", "nct": "NCT03329690", "acronym": null, "title": "DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2019-11-08", "daysToPrimaryCompletion": -2548, "lastUpdate": "2022-03-18", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03329690", "unit": "U-DG01", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-IMP131", "nct": "NCT03125902", "acronym": "IMpassion131", "title": "A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-11-15", "daysToPrimaryCompletion": -2541, "lastUpdate": "2024-03-26", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03125902", "unit": "U-IMP131", "program": "breast", "result": "negative", "pairs": [ "QP-03", "QP-50" ], "forecasts": [] }, { "key": "B-KAITLIN", "nct": "NCT01966471", "acronym": null, "title": "A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2019-11-27", "daysToPrimaryCompletion": -2529, "lastUpdate": "2022-06-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01966471", "unit": "U-KAITLIN", "program": "breast", "result": "negative", "pairs": [ "QP-36" ], "forecasts": [] }, { "key": "T-LENVA211", "nct": "NCT02702388", "acronym": null, "title": "A Trial of Lenvatinib (E7080) in Subjects With Iodine-131 Refractory Differentiated Thyroid Cancer to Evaluate Whether an Oral Starting Dose of 18 Milligram (mg) Daily Will Provide Comparable Efficacy to a 24 mg Starting Dose, But Have a Better Safety Profile", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2019-12-12", "daysToPrimaryCompletion": -2514, "lastUpdate": "2021-11-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02702388", "unit": "U-T-LENVA211", "program": "thyroid", "result": "negative", "pairs": [ "QP-111" ], "forecasts": [] }, { "key": "C-RAPIDO", "nct": "NCT01558921", "acronym": "RAPIDO", "title": "Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2020-03-08", "daysToPrimaryCompletion": -2427, "lastUpdate": "2026-05-01", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01558921", "unit": "U-RAPIDO", "program": "colorectal", "result": "mixed", "pairs": [ "QP-38" ], "forecasts": [] }, { "key": "B-monarchE", "nct": "NCT03155997", "acronym": "monarchE", "title": "Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2020-03-16", "daysToPrimaryCompletion": -2419, "lastUpdate": "2026-04-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03155997", "unit": "U-monarchE", "program": "breast", "result": "positive", "pairs": [ "QP-14", "QP-30", "QP-52" ], "forecasts": [] }, { "key": "B-OlympiA", "nct": "NCT02032823", "acronym": "OlympiA", "title": "Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2020-03-27", "daysToPrimaryCompletion": -2408, "lastUpdate": "2026-07-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02032823", "unit": "U-OlympiA", "program": "breast", "result": "positive", "pairs": [ "QP-14" ], "forecasts": [] }, { "key": "B-ASCENT", "nct": "NCT02574455", "acronym": "ASCENT", "title": "Trial of Sacituzumab Govitecan in Participants With Refractory/Relapsed Metastatic Triple-Negative Breast Cancer (TNBC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2020-03-30", "daysToPrimaryCompletion": -2405, "lastUpdate": "2022-06-15", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02574455", "unit": "U-ASCENT", "program": "breast", "result": "positive", "pairs": [ "QP-33" ], "forecasts": [] }, { "key": "B-IMP130", "nct": "NCT02425891", "acronym": null, "title": "A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2020-04-14", "daysToPrimaryCompletion": -2390, "lastUpdate": "2022-07-19", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02425891", "unit": "U-IMP130", "program": "breast", "result": "positive", "pairs": [ "QP-50" ], "forecasts": [] }, { "key": "G-CM577", "nct": "NCT02743494", "acronym": "CheckMate 577", "title": "An Investigational Immuno-therapy Study of Nivolumab or Placebo in Participants With Resected Esophageal or Gastroesophageal Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2020-05-12", "daysToPrimaryCompletion": -2362, "lastUpdate": "2025-11-18", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02743494", "unit": "U-CM577", "program": "gastric", "result": "positive", "pairs": [ "QP-68", "QP-89" ], "forecasts": [] }, { "key": "G-CM649", "nct": "NCT02872116", "acronym": "CheckMate649", "title": "Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2020-05-27", "daysToPrimaryCompletion": -2347, "lastUpdate": "2025-08-07", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02872116", "unit": "U-CM649", "program": "gastric", "result": "positive", "pairs": [ "QP-09" ], "forecasts": [] }, { "key": "T-COSMIC311", "nct": "NCT03690388", "acronym": null, "title": "A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2020-08-19", "daysToPrimaryCompletion": -2263, "lastUpdate": "2026-10-20", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03690388", "unit": "U-T-COSMIC311", "program": "thyroid", "result": "mixed", "pairs": [ "QP-27" ], "forecasts": [] }, { "key": "B-PENELOPEB", "nct": "NCT01864746", "acronym": "PENELOPE-B", "title": "A Study of Palbociclib in Addition to Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After Neoadjuvant Chemotherapy and Surgery", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2020-08-24", "daysToPrimaryCompletion": -2258, "lastUpdate": "2023-12-12", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01864746", "unit": "U-PENELOPEB", "program": "breast", "result": "negative", "pairs": [ "QP-52" ], "forecasts": [] }, { "key": "G-FIGHT", "nct": "NCT03694522", "acronym": "FIGHT", "title": "A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2020-09-23", "daysToPrimaryCompletion": -2228, "lastUpdate": "2024-02-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03694522", "unit": "U-FIGHT", "program": "gastric", "result": "mixed", "pairs": [ "QP-41" ], "forecasts": [] }, { "key": "B-PALLAS", "nct": "NCT02513394", "acronym": "PALLAS", "title": "PALbociclib CoLlaborative Adjuvant Study", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2020-11", "daysToPrimaryCompletion": -2189, "lastUpdate": "2026-06-15", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02513394", "unit": "U-PALLAS", "program": "breast", "result": "negative", "pairs": [ "QP-04", "QP-52" ], "forecasts": [] }, { "key": "B-IM050", "nct": "NCT03726879", "acronym": "IMpassion050", "title": "A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2021-02-05", "daysToPrimaryCompletion": -2093, "lastUpdate": "2024-11-05", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03726879", "unit": "U-IM050", "program": "breast", "result": "negative", "pairs": [ "QP-70" ], "forecasts": [] }, { "key": "C-KN177", "nct": "NCT02563002", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2021-02-19", "daysToPrimaryCompletion": -2079, "lastUpdate": "2024-10-03", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02563002", "unit": "U-KN177", "program": "colorectal", "result": "mixed", "pairs": [ "QP-23" ], "forecasts": [] }, { "key": "B-EA1131", "nct": "NCT02445391", "acronym": null, "title": "Platinum in Treating Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2021-04-07", "daysToPrimaryCompletion": -2032, "lastUpdate": "2026-10-02", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02445391", "unit": "U-EA1131", "program": "breast", "result": "negative", "pairs": [ "QP-20" ], "forecasts": [] }, { "key": "B-DB03", "nct": "NCT03529110", "acronym": null, "title": "DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2021-05-21", "daysToPrimaryCompletion": -1988, "lastUpdate": "2026-10-07", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03529110", "unit": "U-DB03", "program": "breast", "result": "positive", "pairs": [ "QP-03" ], "forecasts": [] }, { "key": "B-KN355", "nct": "NCT02819518", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2021-06-15", "daysToPrimaryCompletion": -1963, "lastUpdate": "2024-11-27", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02819518", "unit": "U-KN355", "program": "breast", "result": "mixed", "pairs": [ "QP-50" ], "forecasts": [] }, { "key": "B-EMERALD", "nct": "NCT03778931", "acronym": "EMERALD", "title": "Phase 3 Trial of Elacestrant Versus Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2021-08-24", "daysToPrimaryCompletion": -1893, "lastUpdate": "2025-09-15", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03778931", "unit": "U-EMERALD", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-DG02", "nct": "NCT04014075", "acronym": null, "title": "DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2021-11-08", "daysToPrimaryCompletion": -1817, "lastUpdate": "2025-04-03", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04014075", "unit": "U-DG02", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "T-ROAR", "nct": "NCT02034110", "acronym": null, "title": "Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2021-12-10", "daysToPrimaryCompletion": -1785, "lastUpdate": "2023-08-21", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02034110", "unit": "U-T-ROAR", "program": "thyroid", "result": "positive", "pairs": [ "QP-27", "QP-124" ], "forecasts": [] }, { "key": "B-MAINTAIN", "nct": "NCT02632045", "acronym": "MAINTAIN", "title": "Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2022-01-04", "daysToPrimaryCompletion": -1760, "lastUpdate": "2024-12-06", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02632045", "unit": "U-MAINTAIN", "program": "breast", "result": "positive", "pairs": [ "QP-35" ], "forecasts": [] }, { "key": "B-DB04", "nct": "NCT03734029", "acronym": null, "title": "Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-01-11", "daysToPrimaryCompletion": -1753, "lastUpdate": "2026-09-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03734029", "unit": "U-DB04", "program": "breast", "result": "positive", "pairs": [ "QP-10", "QP-11", "QP-51" ], "forecasts": [] }, { "key": "C-PARADIGM", "nct": "NCT02394795", "acronym": "PARADIGM", "title": "Panitumumab and RAS, Diagnostically-useful Gene Mutation for mCRC", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-01-14", "daysToPrimaryCompletion": -1750, "lastUpdate": "2023-11-01", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02394795", "unit": "U-PARADIGM", "program": "colorectal", "result": "positive", "pairs": [ "QP-122" ], "forecasts": [] }, { "key": "B-NeoPACT", "nct": "NCT03639948", "acronym": "NeoPACT", "title": "Neoadjuvant Phase II Study of Pembrolizumab And Carboplatin Plus Docetaxel in Triple Negative Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE2" ], "primaryCompletion": "2022-01-27", "daysToPrimaryCompletion": -1737, "lastUpdate": "2024-04-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03639948", "unit": "U-NeoPACT", "program": "breast", "result": "descriptive", "pairs": [], "forecasts": [] }, { "key": "C-MOUNTAINEER", "nct": "NCT03043313", "acronym": null, "title": "Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2022-03-28", "daysToPrimaryCompletion": -1677, "lastUpdate": "2024-11-26", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03043313", "unit": "U-MOUNTAINEER", "program": "colorectal", "result": "positive", "pairs": [ "QP-51" ], "forecasts": [] }, { "key": "T-DABTHY", "nct": "NCT01723202", "acronym": null, "title": "Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2022-04-15", "daysToPrimaryCompletion": -1659, "lastUpdate": "2025-08-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01723202", "unit": "U-T-DABTHY", "program": "thyroid", "result": "negative", "pairs": [ "QP-124" ], "forecasts": [] }, { "key": "B-DB02", "nct": "NCT03523585", "acronym": null, "title": "DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-06-30", "daysToPrimaryCompletion": -1583, "lastUpdate": "2026-02-27", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03523585", "unit": "U-DB02", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "C-SUNLIGHT", "nct": "NCT04737187", "acronym": "SUNLIGHT", "title": "Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-07-19", "daysToPrimaryCompletion": -1564, "lastUpdate": "2024-09-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04737187", "unit": "U-SUNLIGHT", "program": "colorectal", "result": "positive", "pairs": [ "QP-84" ], "forecasts": [] }, { "key": "C-FRESCO2", "nct": "NCT04322539", "acronym": "FRESCO-2", "title": "A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-07-29", "daysToPrimaryCompletion": -1554, "lastUpdate": "2025-04-04", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04322539", "unit": "U-FRESCO2", "program": "colorectal", "result": "positive", "pairs": [ "QP-84" ], "forecasts": [] }, { "key": "G-SPOTLIGHT", "nct": "NCT03504397", "acronym": "Spotlight", "title": "A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2022-09-09", "daysToPrimaryCompletion": -1512, "lastUpdate": "2026-10-20", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03504397", "unit": "U-SPOTLIGHT", "program": "gastric", "result": "positive", "pairs": [ "QP-07" ], "forecasts": [] }, { "key": "G-KN859", "nct": "NCT03675737", "acronym": null, "title": "Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2022-10-03", "daysToPrimaryCompletion": -1488, "lastUpdate": "2026-02-27", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03675737", "unit": "U-KN859", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "G-GLOW", "nct": "NCT03653507", "acronym": "GLOW", "title": "A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW).", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2022-10-25", "daysToPrimaryCompletion": -1466, "lastUpdate": "2026-09-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03653507", "unit": "U-GLOW", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "C-DCRC02", "nct": "NCT04744831", "acronym": "DESTINY-CRC02", "title": "Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2022-11-01", "daysToPrimaryCompletion": -1459, "lastUpdate": "2026-01-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04744831", "unit": "U-DCRC02", "program": "colorectal", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-PACE", "nct": "NCT03147287", "acronym": null, "title": "Palbociclib After CDK and Endocrine Therapy (PACE)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2022-12-31", "daysToPrimaryCompletion": -1399, "lastUpdate": "2026-09-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03147287", "unit": "U-PACE", "program": "breast", "result": "negative", "pairs": [ "QP-35" ], "forecasts": [] }, { "key": "C-PROSPECT", "nct": "NCT01515787", "acronym": null, "title": "PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery", "status": "UNKNOWN", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2022-12-31", "daysToPrimaryCompletion": -1399, "lastUpdate": "2024-02-02", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01515787", "unit": "U-PROSPECT", "program": "colorectal", "result": "positive", "pairs": [ "QP-38" ], "forecasts": [] }, { "key": "B-CM7FL", "nct": "NCT04109066", "acronym": "CheckMate 7FL", "title": "Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Participants With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2023-01-16", "daysToPrimaryCompletion": -1383, "lastUpdate": "2025-01-08", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04109066", "unit": "U-CM7FL", "program": "breast", "result": "positive", "pairs": [ "QP-64" ], "forecasts": [] }, { "key": "B-RxPONDER", "nct": "NCT01272037", "acronym": null, "title": "Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2023-02-01", "daysToPrimaryCompletion": -1367, "lastUpdate": "2026-10-26", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT01272037", "unit": "U-RxPONDER", "program": "breast", "result": "mixed", "pairs": [ "QP-40", "QP-72" ], "forecasts": [] }, { "key": "G-RAT305", "nct": "NCT03777657", "acronym": null, "title": "Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2023-02-28", "daysToPrimaryCompletion": -1340, "lastUpdate": "2025-02-14", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03777657", "unit": "U-RAT305", "program": "gastric", "result": "positive", "pairs": [ "QP-09" ], "forecasts": [] }, { "key": "B-CAP291", "nct": "NCT04305496", "acronym": "CAPItello-291", "title": "Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2023-05-09", "daysToPrimaryCompletion": -1270, "lastUpdate": "2026-04-30", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04305496", "unit": "U-CAP291", "program": "breast", "result": "mixed", "pairs": [], "forecasts": [] }, { "key": "T-LIBRETTO531", "nct": "NCT04211337", "acronym": "LIBRETTO-531", "title": "A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2023-05-22", "daysToPrimaryCompletion": -1257, "lastUpdate": "2026-03-19", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04211337", "unit": "U-T-LIBRETTO531", "program": "thyroid", "result": "positive", "pairs": [ "QP-27", "QP-80", "QP-82", "QP-112" ], "forecasts": [] }, { "key": "B-HER2CLIMB02", "nct": "NCT03975647", "acronym": null, "title": "A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2023-06-29", "daysToPrimaryCompletion": -1219, "lastUpdate": "2026-07-23", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03975647", "unit": "U-HER2CLIMB02", "program": "breast", "result": "mixed", "pairs": [ "QP-90" ], "forecasts": [] }, { "key": "B-IMP030", "nct": "NCT03498716", "acronym": "IMpassion030", "title": "A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer", "status": "TERMINATED", "phases": [ "PHASE3" ], "primaryCompletion": "2023-08-14", "daysToPrimaryCompletion": -1173, "lastUpdate": "2024-08-21", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03498716", "unit": "U-IMP030", "program": "breast", "result": "negative", "pairs": [ "QP-20" ], "forecasts": [] }, { "key": "B-INAVO120", "nct": "NCT04191499", "acronym": "INAVO120", "title": "A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "primaryCompletion": "2023-09-29", "daysToPrimaryCompletion": -1127, "lastUpdate": "2026-09-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04191499", "unit": "U-INAVO120", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-TROPiCS02", "nct": "NCT03901339", "acronym": "TROPiCS-02", "title": "Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2023-10-20", "daysToPrimaryCompletion": -1106, "lastUpdate": "2024-10-21", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03901339", "unit": "U-TROPiCS02", "program": "breast", "result": "positive", "pairs": [ "QP-11" ], "forecasts": [] }, { "key": "B-UCI1467", "nct": "NCT02436993", "acronym": null, "title": "Phase II Breast Ca Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab or Bevacizumab", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2023-11", "daysToPrimaryCompletion": -1094, "lastUpdate": "2026-11-12", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02436993", "unit": "U-UCI1467", "program": "breast", "result": "descriptive", "pairs": [ "QP-134" ], "forecasts": [] }, { "key": "B-postMONARCH", "nct": "NCT05169567", "acronym": "postMONARCH", "title": "Abemaciclib (LY2835219) Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-02-08", "daysToPrimaryCompletion": -995, "lastUpdate": "2026-10-06", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05169567", "unit": "U-postMONARCH", "program": "breast", "result": "positive", "pairs": [ "QP-35" ], "forecasts": [] }, { "key": "G-KN585", "nct": "NCT03221426", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2024-02-16", "daysToPrimaryCompletion": -987, "lastUpdate": "2026-03-09", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03221426", "unit": "U-KN585", "program": "gastric", "result": "mixed", "pairs": [ "QP-30", "QP-31", "QP-66" ], "forecasts": [] }, { "key": "B-DB06", "nct": "NCT04494425", "acronym": "DB-06", "title": "Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-03-18", "daysToPrimaryCompletion": -956, "lastUpdate": "2026-03-04", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04494425", "unit": "U-DB06", "program": "breast", "result": "positive", "pairs": [ "QP-10" ], "forecasts": [] }, { "key": "G-KN811", "nct": "NCT03615326", "acronym": null, "title": "Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2024-03-20", "daysToPrimaryCompletion": -954, "lastUpdate": "2026-08-26", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03615326", "unit": "U-KN811", "program": "gastric", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "T-ARROW", "nct": "NCT03037385", "acronym": "ARROW", "title": "Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors", "status": "COMPLETED", "phases": [ "PHASE1", "PHASE2" ], "primaryCompletion": "2024-03-21", "daysToPrimaryCompletion": -953, "lastUpdate": "2025-05-31", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03037385", "unit": "U-T-ARROW", "program": "thyroid", "result": "positive", "pairs": [ "QP-82" ], "forecasts": [] }, { "key": "C-NEO", "nct": "NCT03259035", "acronym": null, "title": "NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2024-04-08", "daysToPrimaryCompletion": -935, "lastUpdate": "2026-04-09", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03259035", "unit": "U-NEO", "program": "colorectal", "result": "descriptive", "pairs": [ "QP-44", "QP-59" ], "forecasts": [] }, { "key": "B-PaxalisibBrain", "nct": "NCT03765983", "acronym": null, "title": "GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases", "status": "TERMINATED", "phases": [ "PHASE2" ], "primaryCompletion": "2024-04-29", "daysToPrimaryCompletion": -914, "lastUpdate": "2026-05-27", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03765983", "unit": "U-PaxalisibBrain26", "program": "breast", "result": "negative", "pairs": [ "QP-105" ], "forecasts": [] }, { "key": "B-INTEGRAL", "nct": "NCT04095689", "acronym": "INTEGRAL", "title": "Docetaxel Chemotherapy and Pembrolizumab Plus Interleukin-12 Gene Therapy in Triple Negative Breast Cancer", "status": "TERMINATED", "phases": [ "PHASE2" ], "primaryCompletion": "2024-06-03", "daysToPrimaryCompletion": -879, "lastUpdate": "2026-01-23", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04095689", "unit": "U-INTEGRAL26", "program": "breast", "result": "negative", "pairs": [ "QP-120" ], "forecasts": [] }, { "key": "B-EMBER3", "nct": "NCT04975308", "acronym": "EMBER-3", "title": "A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-06-24", "daysToPrimaryCompletion": -858, "lastUpdate": "2026-07-22", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04975308", "unit": "U-EMBER3", "program": "breast", "result": "mixed", "pairs": [], "forecasts": [] }, { "key": "B-TROPIONB01", "nct": "NCT05104866", "acronym": null, "title": "A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-07-24", "daysToPrimaryCompletion": -828, "lastUpdate": "2026-08-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05104866", "unit": "U-TROPIONB01", "program": "breast", "result": "mixed", "pairs": [ "QP-29" ], "forecasts": [] }, { "key": "C-ALASCCA", "nct": "NCT02647099", "acronym": "ALASCCA", "title": "Adjuvant Low Dose Aspirin in Colorectal Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-08", "daysToPrimaryCompletion": -820, "lastUpdate": "2026-03-13", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02647099", "unit": "U-ALASCCA", "program": "colorectal", "result": "positive", "pairs": [ "QP-108" ], "forecasts": [] }, { "key": "C-CM8HW", "nct": "NCT04008030", "acronym": "CheckMate 8HW", "title": "A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-08-28", "daysToPrimaryCompletion": -793, "lastUpdate": "2026-08-20", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04008030", "unit": "U-CM8HW", "program": "colorectal", "result": "positive", "pairs": [ "QP-23" ], "forecasts": [] }, { "key": "C-LEAP017", "nct": "NCT04776148", "acronym": null, "title": "Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2024-09-27", "daysToPrimaryCompletion": -763, "lastUpdate": "2026-02-05", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04776148", "unit": "U-LEAP017", "program": "colorectal", "result": "negative", "pairs": [ "QP-110" ], "forecasts": [] }, { "key": "B-PATINA", "nct": "NCT02947685", "acronym": "PATINA", "title": "Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2024-10-15", "daysToPrimaryCompletion": -745, "lastUpdate": "2026-10-22", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02947685", "unit": "U-PATINA", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "C-CM142", "nct": "NCT02060188", "acronym": "CheckMate142", "title": "A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread", "status": "COMPLETED", "phases": [ "PHASE2" ], "primaryCompletion": "2024-10-22", "daysToPrimaryCompletion": -738, "lastUpdate": "2025-11-06", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02060188", "unit": "U-CM142", "program": "colorectal", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-VERITAC2", "nct": "NCT05654623", "acronym": "VERITAC-2", "title": "A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-01-31", "daysToPrimaryCompletion": -637, "lastUpdate": "2026-03-18", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05654623", "unit": "U-VERITAC2", "program": "breast", "result": "mixed", "pairs": [ "QP-43" ], "forecasts": [] }, { "key": "C-ATOMIC", "nct": "NCT02912559", "acronym": null, "title": "Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-02-04", "daysToPrimaryCompletion": -633, "lastUpdate": "2026-10-28", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT02912559", "unit": "U-ATOMIC", "program": "colorectal", "result": "positive", "pairs": [ "QP-87" ], "forecasts": [] }, { "key": "C-CHALLENGE", "nct": "NCT00819208", "acronym": "CHALLENGE", "title": "Health Education Materials With/Out a Physical Activity Program for Patients Who Have Undergone Treatment for High-Risk Stage II or Stage III Colon Cancer", "status": "COMPLETED", "phases": [ "NA" ], "primaryCompletion": "2025-02-07", "daysToPrimaryCompletion": -630, "lastUpdate": "2026-04-24", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT00819208", "unit": "U-CHALLENGE", "program": "colorectal", "result": "positive", "pairs": [ "QP-109" ], "forecasts": [] }, { "key": "T-LIBRETTO001", "nct": "NCT03157128", "acronym": "LIBRETTO-001", "title": "A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1", "PHASE2" ], "primaryCompletion": "2025-02-14", "daysToPrimaryCompletion": -623, "lastUpdate": "2026-04-16", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03157128", "unit": "U-T-LIBRETTO001", "program": "thyroid", "result": "positive", "pairs": [ "QP-27", "QP-82" ], "forecasts": [] }, { "key": "C-BREAKWATER", "nct": "NCT04607421", "acronym": null, "title": "A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-03-01", "daysToPrimaryCompletion": -608, "lastUpdate": "2026-06-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT04607421", "unit": "U-BREAKWATER", "program": "colorectal", "result": "positive", "pairs": [ "QP-86" ], "forecasts": [] }, { "key": "B-DB11", "nct": "NCT05113251", "acronym": null, "title": "Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-03-12", "daysToPrimaryCompletion": -597, "lastUpdate": "2026-08-11", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05113251", "unit": "U-DB11", "program": "breast", "result": "positive", "pairs": [], "forecasts": [] }, { "key": "B-QBS72S", "nct": "NCT05305365", "acronym": null, "title": "Study Assessing QBS72S For Treating Brain Metastases", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "primaryCompletion": "2025-06-20", "daysToPrimaryCompletion": -497, "lastUpdate": "2026-10-20", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05305365", "unit": "U-QBS72S26", "program": "breast", "result": "descriptive", "pairs": [ "QP-116" ], "forecasts": [] }, { "key": "C-CODEBREAK300", "nct": "NCT05198934", "acronym": "CodeBreak300", "title": "Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2025-07-16", "daysToPrimaryCompletion": -471, "lastUpdate": "2026-07-22", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05198934", "unit": "U-CodeBreaK300", "program": "colorectal", "result": "positive", "pairs": [ "QP-83" ], "forecasts": [] }, { "key": "B-HER2CLIMB05", "nct": "NCT05132582", "acronym": "HER2CLIMB-05", "title": "A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "primaryCompletion": "2025-09-05", "daysToPrimaryCompletion": -420, "lastUpdate": "2026-09-29", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT05132582", "unit": "U-HER2CLIMB05", "program": "breast", "result": "positive", "pairs": [ "QP-34" ], "forecasts": [] }, { "key": "B-KN522", "nct": "NCT03036488", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)", "status": "COMPLETED", "phases": [ "PHASE3" ], "primaryCompletion": "2025-10-14", "daysToPrimaryCompletion": -381, "lastUpdate": "2026-10-22", "hasResults": true, "stage": "posted", "url": "https://clinicaltrials.gov/study/NCT03036488", "unit": "U-KN522", "program": "breast", "result": "positive", "pairs": [ "QP-30", "QP-31", "QP-64" ], "forecasts": [] } ], "stages": { "upcoming": 15, "past-active": 16, "unknown": 21, "past-closed": 26, "posted": 121 } }, "checks": [ { "id": "PR-001", "file": "PR-001-check-2026-10-03.json", "versionChecked": 1, "checkedAt": "2026-10-03T00:15:43.017942+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": "No eligible new primary EFS result identified in the returned results. Original 2024 pathology paper and secondary reviews are not eligible outcomes. This is not an exhaustive audit of every language or conference." }, { "id": "PR-001", "file": "PR-001-check-2026-10-04.json", "versionChecked": 1, "checkedAt": "2026-10-04T00:17:44.883844+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": "No eligible new ITT co-primary EFS analysis identified in returned primary-source results. The original pathology report and a mechanistic NOX4 subset report do not meet the frozen endpoint/population rule. Search is not exhaustive across all languages or conferences." }, { "id": "PR-001", "file": "PR-001-check-2026-10-05.json", "versionChecked": 1, "checkedAt": "2026-10-05T00:11:25.701168+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": "No eligible new ITT co-primary EFS result found in returned primary records. The original pathology paper and original protocol do not supply a new eligible result. The ASCO PDF returned 403 and PMC presented a browser challenge; methods/SAP were not newly resolved. Search is not exhaustive across languages and conferences." }, { "id": "PR-001", "file": "PR-001-check-2026-10-06.json", "versionChecked": 1, "checkedAt": "2026-10-06T00:13:52.849349+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": "Returned primary records were the original protocol, pathology report and related mechanistic reports; no new eligible ITT co-primary EFS result was found. This is a bounded search, not proof of absence across all languages, sponsor channels or conferences. Prior full-text access failures were not retried today. Original EFS definition, amended SAP and interim boundaries remain held." }, { "id": "PR-001", "file": "PR-001-check-2026-10-07.json", "versionChecked": 1, "checkedAt": "2026-10-07T00:22:30.600726+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": "Bounded primary-domain search returned the prior protocol, pathology and mechanistic reports; no new eligible ITT co-primary EFS was found. Full-text source access failures were not retried. Original EFS definition, amended SAP and interim boundaries remain held." }, { "id": "PR-001", "file": "PR-001-check-2026-10-08.json", "versionChecked": 1, "checkedAt": "2026-10-08T00:08:00.991447+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-09.json", "versionChecked": 1, "checkedAt": "2026-10-09T00:07:01.558653+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-10.json", "versionChecked": 1, "checkedAt": "2026-10-10T00:07:44.266963+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-11.json", "versionChecked": 1, "checkedAt": "2026-10-11T00:10:04.591456+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-12.json", "versionChecked": 1, "checkedAt": "2026-10-12T00:05:23.791748+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-13.json", "versionChecked": 1, "checkedAt": "2026-10-13T00:06:13.032815+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-14.json", "versionChecked": 1, "checkedAt": "2026-10-14T00:15:07.923957+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-15.json", "versionChecked": 1, "checkedAt": "2026-10-15T00:15:13.703290+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-16.json", "versionChecked": 1, "checkedAt": "2026-10-16T00:10:48.830989+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-17.json", "versionChecked": 1, "checkedAt": "2026-10-17T00:11:18.324991+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-18.json", "versionChecked": 1, "checkedAt": "2026-10-18T00:02:36.346272+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-19.json", "versionChecked": 1, "checkedAt": "2026-10-19T00:10:30.572804+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-20.json", "versionChecked": 1, "checkedAt": "2026-10-20T00:10:36.826522+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-21.json", "versionChecked": 1, "checkedAt": "2026-10-21T00:09:28.951634+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-22.json", "versionChecked": 1, "checkedAt": "2026-10-22T00:06:36.630451+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-23.json", "versionChecked": 1, "checkedAt": "2026-10-23T00:08:18.520759+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null }, { "id": "PR-001", "file": "PR-001-check-2026-10-24.json", "versionChecked": 1, "checkedAt": "2026-10-24T00:09:20.494393+00:00", "by": "Codex (GPT-6)", "status": "awaiting_result", "eligibleOutcomeReceived": false, "sources": 3, "finding": null } ], "notes": { "PR-001": { "title": "DRAGON IV · EFS direction forecast", "titleKo": "DRAGON IV · EFS 방향 예측", "notes": [ { "en": "The initial protocol used MPR; the later report and current registry use pCR/EFS. Amendment history, the original SAP and interim boundaries remain unverified.", "ko": "초기 프로토콜은 MPR, 후속 보고와 현행 등록은 pCR/EFS를 제시합니다. 개정 경위·원 SAP·중간분석 경계는 미확인입니다." } ], "links": [ { "en": "Initial protocol", "ko": "초기 프로토콜", "url": "https://pubmed.ncbi.nlm.nih.gov/33490196/" }, { "en": "Published pCR report", "ko": "공개된 pCR 보고", "url": "https://pubmed.ncbi.nlm.nih.gov/39383487/" } ] }, "PR-002": { "title": "NATALEE · overall survival at the next analysis", "titleKo": "NATALEE · 다음 분석의 전체생존", "notes": [ { "en": "The next long-term OS analysis is listed for ESMO 2026 (23–27 October). Whether it is a formal test or a descriptive update was not known when the forecast was frozen.", "ko": "다음 장기 OS 분석은 ESMO 2026(10월 23–27일) 발표로 예고돼 있습니다. 예측을 고정할 때 형식 검정인지 기술적 갱신인지는 알 수 없었습니다." } ] }, "PR-003": { "title": "DESTINY-Breast09 · T-DXd alone vs THP, PFS", "titleKo": "DESTINY-Breast09 · T-DXd 단독 대 THP, PFS", "notes": [ { "en": "Arm A (T-DXd plus pertuzumab placebo) remains blinded against Arm B; so far, only the Arm B versus THP comparison has been reported.", "ko": "Arm A(T-DXd + 퍼투주맙 위약)는 Arm B와 눈가림을 유지하고 있으며, 지금까지는 Arm B 대 THP 비교만 보고됐습니다." } ] }, "PR-004": { "title": "SERENA-6 · final overall survival", "titleKo": "SERENA-6 · 최종 전체생존", "notes": [] }, "PR-005": { "title": "ASCENT-04 · overall survival", "titleKo": "ASCENT-04 · 전체생존", "notes": [] }, "PR-006": { "title": "DESTINY-Breast05 · overall survival", "titleKo": "DESTINY-Breast05 · 전체생존", "notes": [] } }, "judgmentChanges": [ { "id": "QP-42", "state": "held", "scope": "수술 전 면역치료 후 수술 뒤 면역치료 생략의 안전성과 비열등성 판단 보류", "date": "2026-10-02", "by": "Codex (GPT-6)", "reason": "새 질문의 보류 범위를 원출처 설계와 남은 검증 조건에 따라 명시함; 기존 보류 상태는 변경하지 않음", "units": [ "U-GastricAdjuvantIC26", "U-MATTERHORN", "U-ATT5" ] }, { "id": "QP-43", "state": "held", "scope": "변이 선별의 비교 우위·수용체 분해제 순위와 치료 순서 판단 보류", "date": "2026-10-02", "by": "Codex (GPT-6)", "reason": "새 질문의 보류 범위를 원출처 설계와 남은 검증 조건에 따라 명시함; 기존 보류 상태는 변경하지 않음", "units": [ "U-evERA", "U-VERITAC2", "U-SERENA6" ] }, { "id": "QP-44", "state": "held", "scope": "혈액 미검출에 따른 직장 절제 생략의 안전성과 전체 재발 검출 성능 판단 보류", "date": "2026-10-03", "by": "Codex (GPT-6)", "reason": "새 질문의 임상 확대 보류 범위를 명시함; 기존 추적 상태는 보존", "units": [ "U-NEO" ] }, { "id": "QP-45", "state": "held", "scope": "핵 내 단백질 기반 환자 선별과 내성 병용치료의 임상 이득 판단 보류", "date": "2026-10-03", "by": "Codex (GPT-6)", "reason": "새 질문의 임상 확대 보류 범위를 명시함; 기존 추적 상태는 보존", "units": [ "U-FAHCDK9" ] }, { "id": "QP-46", "state": "held", "scope": "치료 후 조직검사 기반 치료 선택의 이득과 독립 예측 성능 판단 보류", "date": "2026-10-04", "by": "Codex (GPT-6)", "reason": "새 질문의 임상 확대 보류 범위를 명시함; 기존 추적 상태 보존", "units": [ "U-P53CRLM26" ] }, { "id": "QP-47", "state": "held", "scope": "소기관 제거 경로 억제에 따른 환자 선별·임상 이득·안전성 판단 보류", "date": "2026-10-04", "by": "Codex (GPT-6)", "reason": "새 질문의 임상 확대 보류 범위를 명시함; 기존 추적 상태 보존", "units": [ "U-TFAMTBK1" ] }, { "id": "QP-48", "state": "held", "scope": "소엽암의 아형별 위험 차이와 조직형 기반 치료 이득 판단 보류", "date": "2026-10-05", "by": "Codex (GPT-6)", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ILCLuminal26" ] }, { "id": "QP-49", "state": "held", "scope": "증식 지표 변화의 확정적 예후 가치와 검사 기반 수술 선택 판단 보류", "date": "2026-10-05", "by": "Codex (GPT-6)", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-Ki67Axilla26" ] }, { "id": "QP-50", "state": "held", "scope": "점수가 낮은 구간과 전체 환자에서의 면역항암 병용 이득 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-KN355" ] }, { "id": "QP-51", "state": "held", "scope": "대장암 HER2 표적치료의 표준치료 대비 이득과 저발현 환자 반응 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-MOUNTAINEER", "U-DCRC01" ] }, { "id": "QP-52", "state": "held", "scope": "같은 계열 약 사이, 진행성과 조기 사이의 생존 이득 일반화 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ML2" ] }, { "id": "QP-53", "state": "held", "scope": "하시모토 갑상선염이 갑상선암을 일으킨다는 해석과 암의 진행을 막는다는 해석 모두 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-AutoimmuneThyCa24", "U-HashimotoOutcome21" ] }, { "id": "QP-54", "state": "held", "scope": "하시모토 갑상선염에서 갑상선암이 생기지 않는 조건의 확정 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-HTYoungFollowup26", "U-JATNodules08", "U-AITCytology14" ] }, { "id": "QP-55", "state": "held", "scope": "갑상선 호르몬 치료가 갑상선암 발생을 줄인다는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-TSHThyCaMeta12", "U-HTTSHLT411" ] }, { "id": "QP-56", "state": "held", "scope": "결절 환자의 연관성을 소아 갑상선염 환자 전체의 발생 위험으로 넓히는 해석 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-AITChildNodule22" ] }, { "id": "QP-57", "state": "held", "scope": "진찰이 정상인 갑상선염 환자에서 정기 초음파가 결과를 개선한다는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ATAPeds15", "U-HTYoungFollowup26" ] }, { "id": "QP-58", "state": "held", "scope": "소아·청소년 갑상선염 환자의 갑상선암 위험을 단일 수치로 제시하는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-HTChildKR21", "U-HTChildTR21", "U-HTChildKR18", "U-BenignThyDK18" ] }, { "id": "QP-59", "state": "held", "scope": "직장암 선행 치료 뒤 경과 관찰이 즉시 수술과 같은 안전성을 가진다는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-OPRA", "U-DOSTrectal" ] }, { "id": "QP-60", "state": "held", "scope": "영상·병리 반응에 따른 항암 생략이 표준 항암과 같은 결과를 낸다는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-PHERGain", "U-APT" ] }, { "id": "QP-61", "state": "held", "scope": "보조 퍼투주맙의 림프절 음성 환자 이득과 전체 생존 이득 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-APHINITY", "U-KATHERINE" ] }, { "id": "QP-62", "state": "held", "scope": "ERBB2 증폭 위암의 공동증폭(주로 CCNE1)이 표적치료 내성의 원인이라는 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-A1", "U-CCNE1TDXd24", "U-HER2GCKwon23" ] }, { "id": "QP-63", "state": "held", "scope": "dMMR 결장암에서 수술 전 항암의 이득과 수술 전 면역항암의 비교 우위 판단 보류", "date": "2026-10-06", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-FOxTROT", "U-NICHE2" ] }, { "id": "QP-64", "state": "held", "scope": "호르몬 수용체 양성 조기 유방암에서 수술 전 면역항암이 재발을 줄인다는 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-KN756", "U-CM7FL" ] }, { "id": "QP-65", "state": "held", "scope": "HER2 양성 조기 유방암에서 화학요법 생략이 가능한 환자를 가려내는 방법 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-KRISTINE", "U-PHERGain" ] }, { "id": "QP-66", "state": "held", "scope": "위암 수술 전후 치료에서 병리 반응 상승이 재발·생존 개선을 뜻한다는 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-PETRARCA", "U-DANTE" ] }, { "id": "QP-67", "state": "held", "scope": "전이 조직의 ESR1 변이 양상이 기관과 검사법이 달라도 성립한다는 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-A2", "U-A5" ] }, { "id": "QP-68", "state": "held", "scope": "위암에서 수술 뒤 면역항암제가 도움이 되는 환자군이 있다는 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-CM577", "U-ATT5" ] }, { "id": "QP-69", "state": "held", "scope": "수술 뒤 혈액 종양 DNA 검사 결과에 따른 치료가 재발·생존을 개선한다는 판단 보류", "date": "2026-10-07", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ctDNAGarcia19", "U-ctDNALate22" ] }, { "id": "QP-70", "state": "held", "scope": "다른 아형·다른 면역치료로 결과를 이식하는 해석, 동등성 및 수치상 하위군 이득의 해석 보류", "date": "2026-10-07", "by": "Codex (GPT-6)", "reason": "이 시험의 음성 결과는 유지한다. 동등성·면역치료 계열 전체로의 이식·하위군 이득 해석은 보류한다.", "units": [ "U-IM050" ] }, { "id": "QP-71", "state": "held", "scope": "관찰 비교로 리보시클립의 우월성을 확정하거나 시간·미래 처방 선택이 함께 해결됐다고 보는 해석 보류", "date": "2026-10-07", "by": "Codex (GPT-6)", "reason": "약물 우월성과 달력 시간·미래 처방 조건을 함께 해결한 비교는 미확인이다.", "units": [ "U-CDK46TTE26" ] }, { "id": "QP-72", "state": "held", "scope": "pN2-3에서 낮은 점수에 따른 항암 생략 또는 관찰된 생존 연관의 인과효과 해석 보류", "date": "2026-10-07", "by": "Codex (GPT-6)", "reason": "pN2-3의 치료 생략과 관찰된 항암 연관의 인과효과 해석을 보류한다.", "units": [ "U-RSNodes26", "U-RxPONDER" ] }, { "id": "QP-73", "state": "held", "scope": "서로 다른 복구 조건을 사람의 공통 병용 치료로 이식하는 해석 보류", "date": "2026-10-08", "by": "Codex (GPT-6)", "reason": "복구에 연결된 실험 결과까지 받아들이되 암종·약제·복구 경로를 분리한다. 위암의 메틸말론산 실험과 유방암의 MPP8 제거 실험은 서로 다른 조건이다. 유전적 제거 또는 동물에서의 감수성 회복을 사람에게 쓸 병용 치료나 완치 근거로 옮기는 해석은 보류한다.", "units": [ "U-GCMMA26", "U-BMPP826" ] }, { "id": "QP-74", "state": "held", "scope": "두 BRCA 결핍군에 공통 FANCM 억제 또는 환자군 예측을 제안하는 해석 보류", "date": "2026-10-08", "by": "Codex (GPT-6)", "reason": "그렇게 묶지 않는다. 이번 세포 체계에서 FANCM은 BRCA1 결핍에는 생존 의존성으로, BRCA2 결핍에는 복제 분기 손상과 PARP 억제제 감수성을 높이는 쪽으로 보고됐다. BRCA2 결핍에서 이를 없앤 결과를 치료 이득으로 읽거나 두 유전자군에 공통 억제를 제안하는 해석은 보류한다.", "units": [ "U-FANCMAdapt26" ] }, { "id": "QP-75", "state": "held", "scope": "모형으로 정의한 감수성·예후 연관을 실제 치료 반응 예측 정확도로 읽는 해석 보류", "date": "2026-10-08", "by": "Codex (GPT-6)", "reason": "모형이 만든 집단의 생물학적 특징을 정리한 결과로 기록한다. 세포주 안의 검증, 환자 자료로 옮긴 예측, 다른 자료의 예후 연관은 각각 다른 평가다. 모형이 정의한 집단을 구분하는 성능이나 세포의 발현 변화를 사람의 치료 반응 예측 정확도로 읽는 해석은 보류한다.", "units": [ "U-GDSCOxali26" ] }, { "id": "QP-76", "state": "held", "scope": "혼합 코호트의 위해 비율을 개인별 위험·치료 차수 간 차이·누적 투여량의 인과효과로 해석하는 범위 보류", "date": "2026-10-09", "by": "Codex (GPT-6)", "reason": "혼합한 관찰 코호트의 비율로 기록하고 치료 맥락·노출 기간·평가 정의를 붙인다. 보조·전이 치료 사이의 차이를 약제의 인과 위해나 개인별 위험으로 해석하는 것은 보류한다. 누적 투여량과의 연관도 노출 시간이 긴 사람에게 사건을 더 발견할 기회가 있었다는 문제를 함께 검토한다.", "units": [ "U-TDM1Liver26" ] }, { "id": "QP-77", "state": "held", "scope": "특정 항체의 점상 염색 연구를 전체 진단 성능·개인 분자/유전성 판정·치료 반응으로 일반화하는 해석 보류", "date": "2026-10-09", "by": "Codex (GPT-6)", "reason": "이 연구의 VENTANA M1 항체와 선택된 검체에서는 점상 염색을 보존으로 읽으면 오류가 생길 수 있다고 기록한다. 다른 항체로 확인한 소실 양상과 내부 대조·검체 부위를 함께 봐야 하는 방법상의 공백이다. 모든 항체의 염색, 분자적 미세부수체 상태, 개인의 유전성 질환이나 면역치료 반응으로 자동 변환하는 해석은 보류한다.", "units": [ "U-MLH1Punctate26" ] }, { "id": "QP-78", "state": "held", "scope": "확대 관찰 코호트의 생존 연관을 독립 재현·개인별 치료 인과 이득·생략 안전성으로 해석하는 범위 보류", "date": "2026-10-10", "by": "Codex (GPT-6)", "reason": "잔존 질환을 포함한 조정 관찰 연관으로 기록한다. 이전 환자 기간을 포함한 확대 분석은 같은 자료원의 후속 보고이므로 독립 재현으로 세지 않는다. 치료 선택·시작 시점·누락과 교란을 검토하기 전에는 개인별 치료 이득이나 생략의 안전성으로 해석하는 범위를 보류한다.", "units": [ "U-ERLowOmission26" ] }, { "id": "QP-79", "state": "held", "scope": "전체 발현/활성 감소의 세포 효과를 엑손 특이 치료·환자 내성 극복·완치로 해석하는 범위 보류", "date": "2026-10-10", "by": "Codex (GPT-6)", "reason": "세포에서 확인한 발현·활성 조절과 노화 상태의 회복을 검증 후보로 기록한다. 전체 단백질을 줄인 효과를 특정 엑손만의 치료 효과로 바꾸거나, 별도 환자 예후 연관을 약제 반응의 검증으로 쓰는 해석은 보류한다. 사람의 선택성·노출·위해·오래 지속되는 종양 제어는 아직 확인되지 않았다.", "units": [ "U-SUV39H2Splice26" ] }, { "id": "QP-80", "state": "held", "scope": "갑상선 수질암에서 반데타닙과 카보잔티닙의 우열 및 전체 생존 이득 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-ZETA", "U-T-EXAM", "U-T-LIBRETTO531" ] }, { "id": "QP-81", "state": "held", "scope": "저위험 유두암 관찰 결과를 암 진단이 없는 사람·소아·더 큰 종양·평생 안전성으로 넓히는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-KoreaThyScreen16" ] }, { "id": "QP-82", "state": "held", "scope": "선택적 RET 억제제 두 약의 우열 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-ARROW", "U-T-LIBRETTO001", "U-T-LIBRETTO531" ] }, { "id": "QP-83", "state": "held", "scope": "KRAS G12C 대장암 병용요법의 전체 생존 이득, 저용량 효과, 약제 간 우열 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-CodeBreaK300", "U-KRYSTAL1CRC" ] }, { "id": "QP-84", "state": "held", "scope": "불응성 대장암 후기 치료의 약제 간 순서와 장기 생존·완치 해석 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-RECOURSE", "U-FRESCO2", "U-SUNLIGHT" ] }, { "id": "QP-85", "state": "held", "scope": "3기 결장암 보조 항암 기간을 요법·위험군에 따라 줄이는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-IDEA18", "U-MOSAIC" ] }, { "id": "QP-86", "state": "held", "scope": "BRAF V600E 대장암 일차 치료의 전체 생존 이득 크기와 항암 병용의 기여 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-BREAKWATER", "U-BEACON" ] }, { "id": "QP-87", "state": "held", "scope": "3기 dMMR 결장암 보조 면역항암의 전체 생존 이득과 다른 전략과의 우열 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ATOMIC", "U-NICHE2" ] }, { "id": "QP-88", "state": "held", "scope": "CDK4/6 억제제 사이의 전체 생존 결과 차이가 약 자체의 차이라는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-PALOMA2", "U-PALOMA3" ] }, { "id": "QP-89", "state": "held", "scope": "식도·접합부 선암에서 수술 전후 항암이 항암방사선 뒤 면역항암제 전략보다 낫다는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ESOPEC", "U-NeoAEGIS" ] }, { "id": "QP-90", "state": "held", "scope": "HER2 양성 전이성 유방암에서 무진행 생존만 개선한 HER2 표적 추가 치료의 생존 이득 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-NALA", "U-HER2CLIMB02" ] }, { "id": "QP-91", "state": "held", "scope": "저위험 분화 갑상선암 요오드 생략을 더 큰 종양·림프절 전이·5년 이후·전절제 미만 수술로 넓히는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-ESTIMABL2", "U-T-IoN", "U-T-HiLo", "U-T-ESTIMABL1" ] }, { "id": "QP-92", "state": "held", "scope": "저위험 유두암 관찰 중 종양 증가를 단일 진행 위험 수치로 제시하는 판단 보류", "date": "2026-10-11", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-PTMCSurveillanceKR18", "U-PMCObserveJP10" ] }, { "id": "QP-94", "state": "held", "scope": "사건별 성능을 전체 사건·현재 모든 기관·개인 추적 전략의 이득 또는 치료 이력의 인과효과로 확대하는 해석 보류", "date": "2026-10-12", "by": "Codex (GPT-6)", "reason": "그렇게 묶지 않는다. 저자가 보고한 국소·구역 재발의 판별 성능과 반대쪽 유방암의 성능을 사건별로 분리한다. 선행 전신치료를 받지 않은 집단에서는 후자의 판별력이 낮았다는 결과도 남긴다. 작은 절대 보정 오차만으로 낮은 위험 구간의 과대예측을 지우거나, 치료 이력이 다른 집단의 성능 차이를 치료의 인과효과로 해석하는 범위는 보류한다. 추적 전략의 환자 이득은 따로 검증해야 한다.", "units": [ "U-INFLUENCEBE26" ] }, { "id": "QP-95", "state": "held", "scope": "실험·환자 상관 신호를 치료 선택·병용 이득·다른 암종의 효과·완치로 확대하는 해석 보류", "date": "2026-10-13", "by": "Codex (GPT-6)", "reason": "환자에서 검증된 병용 치료로 두지 않는다. 위암 모형에서 수용체의 변형·안정화와 항체 내성이 연결되고 차단 개입이 반응을 높였다는 실험 근거를 후보로 기록한다. 환자 예후와의 연관성은 치료 이득과 분리한다. 다른 질환의 약제 승인은 위암에서 필요한 노출·정상 조직 위해·상호작용·생존 이득을 대신하지 않으며 유방암으로의 적용도 보류한다.", "units": [ "U-HER2Lactylation26" ] }, { "id": "QP-96", "state": "held", "scope": "실험·환자 상관 신호를 치료 선택·병용 이득·다른 암종의 효과·완치로 확대하는 해석 보류", "date": "2026-10-13", "by": "Codex (GPT-6)", "reason": "내성과 연결된 후보 신호까지 기록하고 치료 선택 기준으로의 전환은 보류한다. 효소 활성·발현량·인산화 부위는 서로 다른 관측값이며, 환자의 나쁜 예후와 연관된 표지가 특정 치료의 이득을 구분한다는 뜻도 아니다. 치료 중 적응 반응과 장기 내성을 구별하고, 추가 억제의 정상 조직 위해와 환자 결과를 따로 검증해야 한다.", "units": [ "U-CDK1Dynamics26" ] }, { "id": "QP-93", "state": "held", "scope": "외부 병리 예측의 판별력·언어모델 합의·소수 학습을 자체 재현·치료 변경 이득·안전한 임상 운영으로 확대하는 해석 보류", "date": "2026-10-11", "by": "Codex (GPT-6)", "reason": "외부 저자가 보고한 병리 반응의 판별 성능으로 기록한다. 언어모델의 합의와 영상의 설명 가능성은 임상 이득이나 내성 기전의 증명이 아니다. 코호트 독립성·학습 자료 노출·전처리와 모형 고정을 대조하기 전에는 자체 재현으로 세지 않고, 소수 학습 결과를 작은 환자 자료만으로 안전하게 운영할 수 있다는 근거로 해석하는 범위를 보류한다.", "units": [ "U-CLASP26" ] }, { "id": "QP-97", "state": "held", "scope": "잠복기 모형의 설명력을 개별 미래 예측·변이 축적 차단의 임상 이득·재발 예방으로 확대하는 해석 보류", "date": "2026-10-14", "by": "Codex (GPT-6)", "reason": "그렇게 결론내리지 않는다. 원발·전이 종양의 분석에서 변이 시점과 잠복기의 연관을 설명하는 모형으로 기록한다. 검출된 변이가 퍼진 뒤 생겼다는 추론, 개별 환자의 미래 재발 예측, 개입으로 재발을 줄인다는 인과 이득은 각각 검증이 다르다. 표본 선정·검출 감도·이전 치료와 모형 가정을 확인하기 전에는 특정 변이 경로를 예방 치료의 검증된 표적으로 두지 않는다.", "units": [ "U-MetastaticLatency26" ] }, { "id": "QP-98", "state": "held", "scope": "음성 소규모 시험을 기전 전체·현대 치료 순서·재발 예방으로 확대하는 해석과 탐색 생검의 치료 선별 보류", "date": "2026-10-15", "by": "Codex (GPT-6)", "reason": "시험의 내분비 내성 전이성 유방암 맥락에서는 병용이 진행 억제를 개선했다는 근거가 없고 위해가 늘었다고 기록한다. 전임상 활성을 사람의 병용 이득으로 옮긴 기대를 낮춘다. 다만 작은 시험의 차이 미검출을 두 방식의 동등성이나 해당 기전 전체의 부정으로 넓히지 않는다. 현대 치료 순서와 변이별 선택, 재발 예방으로의 외삽은 보류한다.", "units": [ "U-Ganetespib26" ] }, { "id": "QP-99", "state": "held", "scope": "보험 청구 투약 종료를 영상 진행·생존·변이별 비교 약효 및 대체 치료의 이득으로 확대하는 해석 보류", "date": "2026-10-15", "by": "Codex (GPT-6)", "reason": "변이별 투약 지속기간과 분자 신호의 관찰 연관성으로 기록한다. 약을 끝낸 시점은 영상 진행이나 사망과 같지 않고 중단 이유도 다양하다. 이전 치료와 변이의 동반·양, 자료 연결과 누락을 확인하기 전에는 약효의 인과 차이나 대체 약제의 우열로 바꾸지 않는다. 기존 무작위 시험의 결론도 이 관찰로 덮어쓰지 않는다.", "units": [ "U-ESR1VariantTOT26" ] }, { "id": "QP-100", "state": "held", "scope": "상태별 예후 모형의 연관성을 보조치료의 인과 이득·독립 개인 예측·완치로 확대하는 해석 보류", "date": "2026-10-16", "by": "Codex (GPT-6)", "reason": "수술 후 상태별 예후를 설명한 관찰 모형으로 기록하고 보조치료의 인과 이득은 보류한다. 원문의 사망 비율은 재발한 환자들을 분모로 하므로 전체 환자의 사망 비율로 옮기지 않는다. 일정 시점까지 재발 없이 생존한 사람의 조건부 전망도 수술 시점 전체 환자나 미래 개인의 예측과 구분한다. 자료를 다시 분석하거나 치료 효과를 검증한 것으로 세지 않는다.", "units": [ "U-CRLMMultistate26" ] }, { "id": "QP-101", "state": "held", "scope": "공간 신호와 실험 병용 활성을 인간 내성 극복·다른 면역 맥락·임상 준비도로 확대하는 해석 보류", "date": "2026-10-16", "by": "Codex (GPT-6)", "reason": "공간 관측과 실험적 개입이 연결된 후보로 기록하며 인간 병용 효과는 보류한다. 같은 환자의 여러 병변은 독립 환자 수가 아니고, 첫 재평가의 안정질환 포함 반응 분류는 오래 지속되는 임상 이득과 다르다. 면역 결핍 생쥐의 전이 모형 결과를 면역계가 있는 종양이나 사람의 지연 치료로 그대로 옮기지 않는다. 성립하지 않은 모형도 검증 공백으로 보존한다.", "units": [ "U-S100RAGETDXd26" ] }, { "id": "QP-102", "state": "held", "scope": "단일군 장기 생존을 수술 생략의 안전성·비교 생존 이득·완치로 확대하는 해석 보류", "date": "2026-10-17", "by": "Codex (GPT-6)", "reason": "장기 생존이 관찰됐다는 점은 기존 단일군 시험의 후속 근거로 갱신하되, 수술 생략의 안전성과 비교 생존 이득은 보류한다. 전체 등록 집단의 전체 생존과 수술 적격 집단의 무사건 생존은 분모가 다르다. 병리 완전반응, 수술하지 않은 일부 환자의 임상 완전반응, 장기 무사건 상태와 완치를 구분한다. 같은 시험의 후속 논문을 새 임상시험이나 독립 검증으로 세지 않는다.", "units": [ "U-NEONIPIGA" ] }, { "id": "QP-103", "state": "held", "scope": "초기 미생물 병용의 관찰 반응을 제제 단독 기여·사람 내성 극복·비교 이득·완치로 확대하는 해석 보류", "date": "2026-10-18", "by": "Codex (GPT-6)", "reason": "초기 단일군 병용의 관찰 신호로 기록하고 제제 자체의 기여와 비교 이득은 보류한다. 등록부는 다른 항암제 병용도 허용하므로 미생물 제제와 면역치료만의 효과로 읽지 않는다. 등록 계획의 표본 수를 논문의 분석 분모로 바꾸거나 반응 수를 역산하지 않는다. 세포를 제거하는 면역 기전의 동물 실험과 사람의 반응 연관성도 구별한다.", "units": [ "U-AkkMSSCRC26" ] }, { "id": "QP-104", "state": "held", "scope": "계산 잠재 변수를 생물학적 실측·독립 개인 예측·기준모형 대비 우위·치료 이득으로 확대하는 해석 보류", "date": "2026-10-19", "by": "Codex (GPT-6)", "reason": "설명 구조를 가진 계산 모형의 내부 평가로 기록하고, 잠재 변수의 생물학적 실측과 개인 예측의 검증은 보류한다. 문헌의 기준 표현형으로 절대 척도를 고정한 것은 추정 세포량이 실제로 맞음을 뜻하지 않는다. 같은 과거 코호트의 내부 교차검증과 기존 생존모형에 비슷한 순위 성능을 외부 검증이나 우위로 바꾸지 않는다.", "units": [ "U-MechanisticRelapse26" ] }, { "id": "QP-105", "state": "held", "scope": "실패한 뇌전이 병용에서 경로 전체의 무효·뇌척수액 기반 치료 변경 이득으로 확대하는 해석 보류", "date": "2026-10-20", "by": "Codex (GPT-6)", "reason": "시험한 용량과 환자군에서 일차 반응 목표를 달성하지 못한 실패로 기록한다. 뇌 도달이나 전임상 기전만으로 사람의 효능을 유지하지 않는다. 다만 작은 단일군 결과로 모든 경로 억제 전략의 무효를 선언하지 않고, 투여 노출·용량 제한·대상 선택을 다시 구분한다. 뇌척수액 종양 신호의 연관성도 치료 변경의 이득으로 확대하지 않는다.", "units": [ "U-PaxalisibBrain26" ] }, { "id": "QP-106", "state": "held", "scope": "국소 제어의 비열등성을 생존 동등·우월성·조사 생략·장기 위해 부재로 확대하는 해석 보류", "date": "2026-10-20", "by": "Codex (GPT-6)", "reason": "보고된 고위험 수술 후 환자군과 조사 범위에서 국소 제어의 비열등성과 급성 피부 독성 감소를 지지하는 결과로 기록한다. 생존의 우월성이나 동등성, 림프절 조사 생략, 드문 장기 심장 위해의 부재로 확대하는 판단은 보류한다. 무작위 배정 전체와 수정 분석 집단의 차이도 확인한다.", "units": [ "U-HypoMastIMNI26" ] }, { "id": "QP-107", "state": "held", "scope": "단일군 장기 경과를 수술 전 치료의 독립 기여·비교 이득·완치로 확대하는 해석 보류", "date": "2026-10-20", "by": "Codex (GPT-6)", "reason": "한 코호트의 장기 경과와 치료 이행을 보여 주는 자료로 기록한다. 수술 전 치료·수술·수술 후 치료와 환자 선택이 함께 있어 짧은 수술 전 과정의 독립 기여와 다른 요법 대비 이득은 보류한다. 생존자를 오래 관찰한 사실과 전체 환자의 완치도 구분한다.", "units": [ "U-nacGSOXLong26" ] }, { "id": "QP-108", "state": "held", "scope": "PI3K 변이 대장암 아스피린의 전체 생존 이득과 변이 없는 환자·이차 변이군으로의 확대 판단 보류", "date": "2026-10-20", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-ALASCCA" ] }, { "id": "QP-109", "state": "held", "scope": "운동 프로그램 이득의 전체 생존 확정, 운동량 기준, 직장암·전이암·다른 암 확대 판단 보류", "date": "2026-10-20", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-CHALLENGE" ] }, { "id": "QP-110", "state": "held", "scope": "pMMR 전이 대장암 면역항암 병용의 이득 판단 보류", "date": "2026-10-20", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-LEAP017", "U-AtezoTRIBE", "U-AkkMSSCRC26" ] }, { "id": "QP-111", "state": "held", "scope": "렌바티닙 저용량 시작 전략의 이득 판단 보류", "date": "2026-10-20", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-LENVA211", "U-T-SELECT" ] }, { "id": "QP-112", "state": "held", "scope": "갑상선암 다중 표적 억제제의 시험 간 순위 판단 보류", "date": "2026-10-20", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-Donafenib23", "U-T-ALTER01031", "U-T-SELECT", "U-T-DECISION", "U-T-ZETA", "U-T-EXAM", "U-T-LIBRETTO531" ] }, { "id": "QP-113", "state": "held", "scope": "기저 폐 소견의 관찰 연관성을 개인 위험·치료 배제나 감시 전략의 이득으로 확대하는 해석 보류", "date": "2026-10-21", "by": "Codex (GPT-6)", "reason": "치료를 받은 한 코호트에서의 위해 연관성으로 기록한다. 미세한 소견도 무시할 수 없다는 연구 질문을 남기되 개인의 위험 확률이나 치료 배제·검사 전략의 이득으로 확대하는 판단은 보류한다. 모호한 소견과 확실한 소견의 차이가 유의하지 않았다는 결과도 두 집단의 동일함을 증명하지 않는다.", "units": [ "U-TDXdILA26" ] }, { "id": "QP-114", "state": "held", "scope": "호산구의 예후 연관성을 차등 치료 선택 검증·혈구 증가 개입의 사람 재발 예방으로 확대하는 해석 보류", "date": "2026-10-21", "by": "Codex (GPT-6)", "reason": "예후 연관성과 차등 치료 이득을 구분해 기록한다. 큰 확장 코호트와 가중 분석이 있어도 치료 배정·기점·문턱값·상호작용을 확인하기 전 선택 지표로서의 검증은 보류한다. 생쥐에서 호산구를 옮긴 결과를 사람의 혈구 수를 높여 재발을 막는 효과로 바꾸지 않는다.", "units": [ "U-EosinophilHR26" ] }, { "id": "QP-115", "state": "held", "scope": "시험관 구성 점수를 사람의 치료 성공확률·영상 반응·치료 축소 안전성으로 확대하는 해석 보류", "date": "2026-10-21", "by": "Codex (GPT-6)", "reason": "약물별 취약성과 병용 기여를 나눠 보는 실험적 점수로 기록한다. 점수의 이름에 확률이 들어가도 사람의 결과에 맞춰 보정된 확률은 아니며, 시험관의 반응 유사 구간도 환자의 영상 반응이 아니다. 약제 구성 축소나 개인 선택의 안전성을 확정하는 해석은 보류한다.", "units": [ "U-ACTOrganoid26" ] }, { "id": "QP-116", "state": "held", "scope": "구획별 단일군 신호를 한 반응률·약제 우열·임상 이득·완치로 합치는 해석 보류", "date": "2026-10-21", "by": "Codex (GPT-6)", "reason": "같은 시험의 다른 코호트로 연결하고 질환 구획·평가변수·분모를 나눠 기록한다. 연수막 질환의 안정 또는 호전은 확인된 객관적 반응과 같지 않으며, 실질 뇌전이의 반응 실패를 다른 코호트의 분모에 옮기지 않는다. 뇌척수액에서 약물이 검출된 사실도 임상 이득이나 완치를 확정하지 않는다.", "units": [ "U-QBS72S26" ] }, { "id": "QP-117", "state": "held", "scope": "완전반응과 비수술 관리를 선택한 집단의 관찰 비교로 기록한다. 생존 차이를 뚜렷하게 찾지 못한 결과는 동등성이나 비열등성의 입증이 아니다. 반응 확인과 치료 시점·선택·추적 차이를 보존하며, 유지 치료나 수술을 생략하는 전략의 안전성과 완치 확대는 보류한다.", "date": "2026-10-22", "by": "Codex (GPT-6)", "reason": "원출처의 관찰·기전 해석과 임상 확대를 구분한 새 판단", "units": [ "U-PD1MaintenanceCRC26" ] }, { "id": "QP-118", "state": "held", "scope": "지방 이용과 세포 사멸 회피를 잇는 기전 가설로 기록한다. 환자 조직의 발현과 실험 모델의 경로 조작을 사람의 전이 치료 효과로 확대하지 않는다. 표적 특이성·구제 실험·노출·위해를 원 방법에서 확인하기 전 약제나 임상 효능의 순위를 정하는 판단은 보류한다.", "date": "2026-10-22", "by": "Codex (GPT-6)", "reason": "원출처의 관찰·기전 해석과 임상 확대를 구분한 새 판단", "units": [ "U-FABP4Peritoneal26" ] }, { "id": "QP-119", "state": "held", "scope": "잔존 병변을 가진 환자에서의 분류 변화와 예후 연관성으로 기록한다. 생검과 수술 검체의 차이를 치료가 일으킨 생물학적 변화로 단정하지 않고, 선택된 재판독·표본 구성·판독 변동을 함께 살핀다. 재검사에 따라 약제를 정하는 전략의 이득이나 전이암 결과의 이식은 보류한다.", "date": "2026-10-23", "by": "Codex (GPT-6)", "reason": "원출처의 분류 변화·예후와 재검사 기반 치료 이득을 구분한 새 판단", "units": [ "U-HER2ResidualDiscord26" ] }, { "id": "QP-120", "state": "held", "scope": "이 병용·투여 조건에서 관찰된 위해와 조기 종료를 실패 근거로 보존한다. 이를 용량 조절이 안전하다는 근거나 면역 경로 전체의 무효로 바꾸지 않는다. 특정 성분의 인과 기여와 다른 전달 방식의 이득은 구분해 보류한다.", "date": "2026-10-24", "by": "Codex (GPT-6)", "reason": "원출처의 실패·장기 추적과 임상 확대의 범위를 구분한 새 판단", "units": [ "U-INTEGRAL26" ] }, { "id": "QP-121", "state": "held", "scope": "같은 시험의 성숙한 추적을 기존 근거에 연결해 무병생존 미확인이라는 옛 한계를 갱신한다. 동시에 수술을 포함한 전략·계획 준수 집단·서로 다른 평가 기점과 탐색적 전체 생존을 보존한다. 관찰 기간에 사건이 없다는 결과를 영구적인 재발 위험 소멸이나 수술 생략의 검증으로 확대하는 판단은 보류한다.", "date": "2026-10-24", "by": "Codex (GPT-6)", "reason": "원출처의 실패·장기 추적과 임상 확대의 범위를 구분한 새 판단", "units": [ "U-NICHE2" ] }, { "id": "QP-122", "state": "held", "scope": "RAS 야생형 전이성 대장암 전체에서 일차 항EGFR 항체의 생존 우위 판단 보류", "date": "2026-10-30", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-FIRE3", "U-CALGB80405", "U-PARADIGM" ] }, { "id": "QP-123", "state": "held", "scope": "전이성 대장암 강화·보조 항암에서 무병 생존·반응 지표를 생존 이득으로 읽는 판단 보류", "date": "2026-10-30", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-TRIPLETE", "U-JCOG0603", "U-IDEA18" ] }, { "id": "QP-124", "state": "held", "scope": "방사성요오드 불응 BRAF 변이 분화 갑상선암에서 MEK 억제제 추가 이득 판단 보류", "date": "2026-10-30", "by": "Claude", "reason": "새 질문의 보류 범위와 독립 확인 조건을 명시함; 기존 추적 상태 보존", "units": [ "U-T-DABTHY", "U-T-ROAR" ] }, { "id": "QP-130", "state": "held", "scope": "병리반응 개선을 생존 이득·동등성 또는 위해 감소로 확대하는 판단 보류", "date": "2026-11-12", "by": "Codex (GPT-6)", "reason": "생존 우월성 미확인·신경독성 신호·등록 불일치를 함께 확인했다.", "units": [ "U-NabDDHR26" ] }, { "id": "QP-131", "state": "held", "scope": "예후 연관성을 검사 기반 치료·수술 선택의 이득으로 바꾸는 판단 보류", "date": "2026-11-12", "by": "Codex (GPT-6)", "reason": "단변량 분석·가변 채혈 시점·검사 확보에 따른 선택의 한계가 있다.", "units": [ "U-CRPMctDNA26" ] }, { "id": "QP-132", "state": "held", "scope": "반복 검사 음성에 따른 치료 축소·중단의 안전성과 완치 판단 보류", "date": "2026-11-13", "by": "Codex (GPT-6)", "reason": "장기 반응 선별 코호트이며 검사 이후 진행 사례가 있고 무작위 치료 비교가 없다.", "units": [ "U-HER2CR26" ] }, { "id": "QP-133", "state": "held", "scope": "합성 반응 지표에 따른 추가 면역치료 이득·수술 생략 판단 보류", "date": "2026-11-13", "by": "Codex (GPT-6)", "reason": "수술과 비수술 집단에 다른 반응 기준을 적용한 단일군 시험이다.", "units": [ "U-CA2098M4" ] }, { "id": "QP-134", "state": "held", "scope": "허투별 비무작위 군 비교를 통한 약제 우열 판단 보류", "date": "2026-11-13", "by": "Codex (GPT-6)", "reason": "허투 상태와 배정 치료가 함께 다르고 일부 평가변수는 수치가 게시되지 않았다.", "units": [ "U-UCI1467" ] } ], "correctionReviews": [ { "pmid": "40088908", "forPmid": "38906161", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/langas/article/PIIS2468-1253(25)00047-0/fulltext", "summary": "Treatment-discontinuation wording was corrected to treatment-related adverse events. Other corrections concern treatment completion, rounding, a figure confidence-level label, diarrhoea and deaths. The current abstract retains the cited primary relapse-free-survival estimate and adjusted interval. U-ATT5 now uses the corrected safety wording." }, { "pmid": null, "forPmid": "17978289", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070056", "summary": "The notice changes the third S-1 entry in Figure 1A from270to370. It does not amend the abstract efficacy or safety estimates used here. Original and five-year trial reports remain one evidence unit." }, { "pmid": "38867085", "forPmid": "37548812", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://link.springer.com/article/10.1007/s10120-024-01519-0", "summary": "The Results paragraph had mislabeled 190 and 236 as patients with recurrence and separately cited deaths. The notice replaces this with 426 observed events during five years: 190 with S-1 plus docetaxel and 236 with S-1 alone. The article was corrected as of May 22, 2024. The curated unit avoids the erroneous recurrence counts; the notice does not amend its abstract survival estimates." }, { "pmid": "37766422", "forPmid": "37184928", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://academic.oup.com/jnci/article/115/11/1437/7284424", "summary": "The notice corrects a Discussion citation about estrogen levels and bone mineral density, adds the correct study and an endocrine-therapy toxicity systematic review to the bibliography, and renumbers subsequent citations. It does not amend the efficacy or safety estimates in the abstract used for U-NSABPB42." }, { "pmid": null, "forPmid": "23219286", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60252-4/fulltext", "summary": "Corrects the control cardiac-event count, transposes receptor-group labels in specified appendix plots, and restores omitted authors, collaborators and centers. The proposed unit omits the affected cardiac estimate and appendix curves; the reported ER-positive recurrence and breast-cancer mortality and selected noncardiac harms are outside the notice scope." }, { "pmid": "28457627", "forPmid": "23219286", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8889022/", "summary": "The audit update is limited in the main paper to ischemic heart disease, non-breast-cancer mortality, and mortality with unknown or any ER status. The proposed unit omits those estimates; ER-positive recurrence and breast-cancer mortality and selected noncardiac harms are outside the stated scope." }, { "pmid": "30614468", "forPmid": "30509771", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30926-4/fulltext", "summary": "The notice corrects only the article title, applied online January 3, 2019; the printed version is correct. It does not amend the primary DFS estimates or significance threshold used here." }, { "pmid": "40023649", "forPmid": "39874977", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00352-6/fulltext", "summary": "The notice states that the appendix was corrected as of February 27, 2025, without specifying individual changes. The proposed unit makes no appendix-derived claims. Its central-confirmation denominators, PFS estimate and safety figures match the current publisher abstract and saved PubMed abstract. Review is limited to these abstract-supported claims and does not certify the appendix." }, { "pmid": "31881136", "forPmid": "31825569", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx190039", "summary": "The Safety subsection is replaced with a more specific account of one patient who met laboratory Hy’s-law criteria, recovered after dose modification, continued treatment, and was subsequently judged by an independent hepatology review not to be a true Hy’s-law case. The notice concerns characterization of a liver-safety event, not the efficacy endpoint. The current unit uses PFS estimates only and omits the affected individual liver-event classification." }, { "pmid": "39637898", "forPmid": "37875143", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00650-8/fulltext", "summary": "The correction restores an omitted hazard-ratio data point for the no-liver-metastases subgroup in Figure 2D. It was applied online on December 2, 2024. The current unit uses ITT overall survival and omits the affected subgroup figure." }, { "pmid": "41931063", "forPmid": "41370739", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx260006", "summary": "The notice restores a corrupted Discussion passage about activity in tumors with lower IHC scores plus ISH amplification and the predominance of distant invasive recurrences. It specifies distant-event counts for the two arms. It does not amend the abstract IDFS or ILD estimates used in the current unit. The stale full-notice-unreviewed wording in the unit limits should be updated when this review is integrated." }, { "pmid": "26559595", "forPmid": "25564897", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx150037", "summary": "In the Results adverse-events subsection, grade3 neuropathy during combination treatment was corrected from14 to13 patients (3.2%,95%CI1.7–5.4). The notice states the online article is corrected. Uses corrected13 and3.2%, matching the current official PubMed abstract. No efficacy result is identified as changed by this notice." }, { "pmid": "31044719", "forPmid": "30718072", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30244-X/fulltext", "summary": "Table 3 should give the ramucirumab plus chemotherapy group grade 4 gastrointestinal-haemorrhage event percentage as 1%; the correction was applied April 30, 2019. The existing unit cites PFS and OS only. The corrected adverse-event percentage is not added to its abstract-only numeric claim. A separate saved-abstract context issue is recorded below." }, { "pmid": "37481269", "forPmid": "37068504", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01481-2/fulltext", "summary": "The statistical-analysis and eligibility sections are directed to corrected appendix page ranges, and the appendix itself was corrected as of July 20, 2023. This review does not certify the corrected appendix or its statistical-analysis plan. Existing efficacy figures were checked against the current public publisher abstract." }, { "pmid": "38101428", "forPmid": "37068504", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02762-9/fulltext", "summary": "The notice replaces grade-specific descriptions of the most common nausea, vomiting and decreased appetite with all-grade wording, explains more nausea/vomiting-related discontinuation with zolbetuximab, and states that small gastro-oesophageal-junction subgroups do not support PFS or OS conclusions. It also corrects appendix references, a White-race placebo event count in a forest plot, adds a dyspnoea row, revises Discussion wording and amends the appendix. Corrections were applied December 12, 2023. The stored PubMed abstract still uses the superseded grade-specific wording. The current publisher abstract uses all-grade. Keep the original source bytes and explicitly identify this discrepancy; do not infer a GEJ-specific efficacy benefit from the overall trial. No appendix-derived claim is included." }, { "pmid": "37364222", "forPmid": "35584336", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://ascopubs.org/doi/10.1200/JCO.23.01239", "summary": "The fulvestrant-only Kaplan-Meier curves in Figure 1 panels C and D were replaced after incorrectly duplicating panels A and B. Supplementary Figure S5 panel B changes a six-month overall-survival confidence interval to 88.7-97.8, and supplementary Table S3 changes the all-patient hazard-ratio confidence interval to 0.63-0.95. The correction was applied June 26, 2023. The existing claim uses the primary PFS hazard ratios for all patients and the ESR1-mutant population, both supported by the saved abstract. It does not cite the fulvestrant-only curves, six-month OS interval or supplementary hazard ratio. This notice does not amend the two cited primary PFS hazard ratios. Do not transfer the primary all-patient comparison to a fulvestrant-only comparison, or imply that the corrected curves and supplementary estimates were independently reproduced." }, { "pmid": null, "forPmid": "23020162", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx130019", "summary": "The aggregate adverse-event category must include grade 3 and all higher grades, rather than only grades 3 and 4. The correction applies to the Abstract Results, Results Safety paragraph, two Table 3 column headings and its second footnote. The current claim reports only independently reviewed PFS medians and a hazard ratio. These are unchanged in the current publisher abstract. The saved PubMed abstract retains superseded safety-category wording; preserving it without context risks later reusing an incorrect category. Preserve the raw PubMed source. Add the correction scope to limits and distinguish the aggregate grade-at-least-3 category from a grade-3-or-4-only category. No safety-equivalence claim or patient-level reanalysis follows from this review." }, { "pmid": null, "forPmid": "17192538", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070016", "summary": "A missing footnote in Table 3 reports grade-4 adverse events: 13 events among 10 combination-arm patients and 16 events among 11 capecitabine-only patients. The notice describes the between-arm differences as not statistically significant and states that the table was corrected online. The correction concerns the adverse-event table and does not amend the initial time-to-progression estimates cited in the unit. The later final-OS paper is outside this notice and was not reaudited in this review. The current limits still incorrectly say the complete notice remains unread. Replace only the stale full-notice review-status passage; retain the early-stopping, crossover, toxicity and historical-comparator limitations. The corrected footnote is not evidence of equivalence or absence of toxicity and its event counts are not added to the abstract-only efficacy claim." }, { "pmid": "30894267", "forPmid": "28215665", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32771-5/fulltext", "summary": "The notice corrects declarations of interest for several named authors and states that the online version was updated. It does not identify changes to efficacy or safety results. The numerical DFS and OS statements in the proposed unit therefore remain supported by the saved final abstract." }, { "pmid": "30507432", "forPmid": "30355453", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30843-X/fulltext", "summary": "Several Figure 3 points and an x-axis scale value were corrected, as was an x-axis scale value in appendix Figure 1. The notice also mentions other minor errors without itemizing them; changes were applied online on November 28, 2018. The proposed claim uses the overall-survival and adverse-event values in the saved official abstract; these were also directly checked against the current publisher abstract. No subgroup or corrected-figure estimate is used. The unspecified minor errors are not claimed to have been independently audited." }, { "pmid": "33539749", "forPmid": "33301740", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30781-6/fulltext", "summary": "Figure 1 must identify 185 of the 187 standard-care patients receiving adjuvant chemotherapy as receiving it according to hospital policy. The correction was applied online on February 1, 2021. This flow-diagram classification correction is not used to alter the primary disease-related treatment-failure estimates or the separate later locoregional-failure report. Optional adjuvant therapy remains a feature of the standard-care strategy; the unit does not infer a randomized effect of receiving adjuvant chemotherapy." }, { "pmid": "34339653", "forPmid": "34252374", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00417-4/fulltext", "summary": "A Results appendix page reference was changed. Two erroneous group labels in the Table 2 legend were replaced by adjuvant-SOX, and Appendix 2 was updated. Changes were applied online on July 30, 2021; the notice states the printed version was correct. The proposed unit uses the reported modified intention-to-treat disease-free-survival comparisons and the subsequent final overall-survival report. No estimate is extracted from the corrected table legend or appendix; those underlying artifacts were not independently audited." }, { "pmid": "39914427", "forPmid": "34252374", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00015-4/fulltext", "summary": "The primary-endpoint sentence in Summary Methods was corrected: the superiority comparison is perioperative-SOX versus adjuvant-CapOx, while the non-inferiority comparison is adjuvant-SOX versus adjuvant-CapOx with an HR margin of 1.33. The change was applied online on February 3, 2025. The saved primary PubMed abstract still names adjuvant-SOX as the superiority comparator. The current publisher abstract and final report instead agree with the correction. The raw PubMed record is preserved; the proposed claim uses the corrected adjuvant-CapOx comparison and does not infer superiority between the two SOX strategies." }, { "pmid": null, "forPmid": "20728210", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61919-8/fulltext", "summary": "The chemotherapy-arm median overall survival in Figure 4A must read 11.1 months. The notice states that the online correction was applied on October 8, 2010. The current unit already reports chemotherapy-arm median overall survival of 11.1 months. The current official publisher abstract also reports 13.8 versus 11.1 months and HR 0.74. The notice changes an efficacy figure value, but the existing unit already agrees with the corrected value." }, { "pmid": null, "forPmid": "22588877", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://aacrjournals.org/cancerdiscovery/article/2/10/960/2824/Correction-The-cBio-Cancer-Genomics-Portal-An-Open", "summary": "The Grant Support statement omitted the Starr Cancer Consortium funding, grant I5-A500, for the integration with Integrative Genomics Viewer (IGV). The correction adds funding attribution and does not amend the current description of the cancer-genomics platform. It does not establish or revalidate the local statement that IATHEON A1 and A2 use the API." }, { "pmid": "28792849", "forPmid": "28578601", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx170012", "summary": "The print edition omitted the authors’ disclosure statement. The notice supplies those conflicts of interest and says the online article is correct. It does not report an efficacy or safety estimate correction." }, { "pmid": "30586508", "forPmid": "27717303", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx180043", "summary": "The disclosure statement and disclosure forms were updated to add disclosures for three authors; the notice says the article is correct online. It does not report an efficacy or safety estimate correction." }, { "pmid": "38070948", "forPmid": "37086745", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02709-5/fulltext", "summary": "Subheadings under Visceral disease in figure 2 (subgroup display) were corrected online. The notice does not change the overall progression-free survival, safety or interstitial lung disease figures used in this record; subgroup values are not adopted here." }, { "pmid": "38460989", "forPmid": "37086745", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00420-3/fulltext", "summary": "One author's affiliation and the formatting of another author's name were corrected online. It does not report an efficacy or safety estimate correction." }, { "pmid": "28700263", "forPmid": "28581356", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx170011", "summary": "The authors' disclosure statement had been omitted from the print edition and was supplied. It does not report an efficacy or safety estimate correction." }, { "pmid": "30338958", "forPmid": "28581356", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx180036", "summary": "Disclosure information for one author was inaccurate and an expanded disclosure statement was added; the editors noted that the author had failed to disclose financial associations. It does not report an efficacy or safety estimate correction." }, { "pmid": "28884691", "forPmid": "28734759", "type": "ErratumIn", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30638-1/fulltext", "summary": "The 86% (95% CI 62-95) figure for responses lasting 12 months was relabelled as a Kaplan-Meier 12-month estimate, and an earlier database lock date was corrected to September 2016. The numerical estimates themselves were not changed." }, { "pmid": "36791183", "forPmid": "33789008", "type": "ErratumIn", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx220014", "summary": "A baseline table row was relabelled from tumour location at initial diagnosis to tumour location at trial entry, and its patient counts by location were corrected in both groups; a figure label was corrected likewise. It does not report an efficacy or safety estimate correction." }, { "pmid": "40140623", "forPmid": "39843940", "type": "ErratumIn", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://www.nature.com/articles/s41591-025-03666-y", "summary": "Missing subgroup labels were added to one figure, the y-axis labels of the progression-free survival figure were corrected from overall survival, and the hazard ratio shown in that figure was corrected to 0.53, which is the value in the abstract." }, { "pmid": "31917389", "forPmid": "31369045", "type": "ErratumIn", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11845095/", "summary": "Three figures in the Results were corrected: validated assays were developed for 90.9% of mutations rather than 91.5%; of 29 patients who relapsed, 23 (79.3%, not 88.4%) had prior ctDNA detection and 6 (20.7%, not 21.6%) relapsed without it. The hazard ratios, lead time and site-specific detection counts in the abstract were not changed." }, { "pmid": "39938112", "forPmid": "37870968", "type": "ErratumIn", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx240006", "summary": "A reanalysis with a later data snapshot and the same data cutoff changed abstract values: median progression-free survival 3.9 months (95% CI 3.6 to 5.7) for the 240-mg group and 2.0 months for standard care, hazard ratios 0.48 (95% CI 0.30 to 0.78; P=0.005) for 960 mg and 0.59 (95% CI 0.37 to 0.95; P=0.036) for 240 mg, and the conclusion now attributes significantly longer progression-free survival to the 960-mg dose only. The library unit uses the corrected values and links the notice." }, { "pmid": "37367990", "forPmid": "37071094", "type": "ErratumIn", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10300671/", "summary": "A Discussion sentence about second-line treatment duration in another trial (FIRE-3) was reworded from longer to shorter, one reference was replaced and Supplement 3 was changed. No abstract value used in the library unit was changed." }, { "pmid": "34534460", "forPmid": "34118198", "type": "ErratumIn", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00247-3/fulltext", "summary": "The first sentence of the Introduction (share of medullary cancer among thyroid cancers) was reworded. No result used in the library unit was changed." }, { "pmid": "37973164", "forPmid": "37907210", "type": "ErratumIn", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10652813/", "summary": "One author's affiliation was corrected. It does not report an efficacy or safety estimate correction." }, { "pmid": "27760322", "forPmid": "27149842", "type": "ErratumIn", "reviewedAt": "2026-10-20", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5638785/", "summary": "Supplementary Table S3 was replaced with a version that includes all somatic mutations used in the analyses. No abstract value was changed. The library uses this study's public portal mutation data for analysis A8 and cites the paper only as the data source." }, { "pmid": "42001850", "forPmid": "41895280", "type": "ErratumIn", "reviewedAt": "2026-10-21", "by": "Claude", "url": "https://www.cell.com/cancer-cell/fulltext/S1535-6108(26)00217-5", "summary": "Only the Received date was corrected (to the original submission date of 26 April 2024). No result, data or abstract value was changed. The library cites the paper as the source of the MSK-IMPACT 50K data used in analysis A9." }, { "pmid": "42817702", "forPmid": "41661218", "type": "ErratumIn", "reviewedAt": "2026-10-24", "by": "Codex (GPT-6)", "url": "https://aacrjournals.org/clincancerres/article/32/19/4504/788418/Correction-A-Phase-II-Study-of-Docetaxel-and", "summary": "The notice adds the omitted author Ann C. Anselme and updates author contributions/disclosures. It does not amend the abstract efficacy or safety figures used here. The separate parent-body response percentage and registry response-definition discrepancy remain explicitly unresolved." } ] }, "programs": [ { "id": "gastric", "name": "Gastric Cancer", "short": "Gastric", "status": "Active", "color": "dab", "summary": "Targeted therapy for gastric and gastro-oesophageal junction adenocarcinoma: HER2, CLDN18.2, the PD-1 axis with its biomarkers, VEGFR2, resistance after first-line HER2 therapy, and recurrence and metastasis.", "axes": [ "HER2 and HER2 loss after trastuzumab", "CLDN18.2 antibodies and cell therapy", "PD-1 blockade and PD-L1 / MSI-H biomarkers", "VEGFR2 in later lines", "Tumour heterogeneity and co-amplification", "Peritoneal metastasis and recurrence" ], "files": [ "RF-G1" ], "subtypes": [ "G-HER2", "G-HER2NEG", "G-CLDN", "G-PDL1", "G-MSI", "G-TCGA" ] }, { "id": "breast", "name": "Breast Cancer", "short": "Breast", "status": "Active", "color": "eosin", "summary": "Targeted therapy by subtype — HER2-positive, HR-positive/HER2-negative and triple-negative — with HER2 expression level tracked as a separate attribute that cuts across those subtypes. Endocrine resistance, recurrence after adjuvant therapy and response differences are standing questions.", "axes": [ "HER2-positive: antibodies, ADCs and TKIs", "HR+/HER2−: CDK4/6, PI3K/AKT, ESR1-directed therapy", "Triple-negative: immunotherapy and TROP2 ADCs", "HER2-low and HER2-ultralow across subtypes", "Endocrine resistance and ESR1 mutations", "Adjuvant therapy and recurrence" ], "files": [ "RF-B1" ], "subtypes": [ "B-HER2POS", "B-HRPOS", "B-TNBC" ] }, { "id": "colorectal", "name": "Colorectal Cancer", "short": "Colorectal", "status": "Partial", "color": "dab", "summary": "Authorised extension alongside the gastric and breast core programmes. The starter library separates recurrence and residual-disease evidence from immunotherapy evidence in study-defined dMMR/MSI-H colon and rectal cancer. It does not cover all colorectal treatment settings.", "axes": [ "Recurrence and ctDNA-guided research questions", "Study-defined dMMR / MSI-H populations", "Colon and rectal settings kept separate", "Durable control and curative approaches: validation still required" ], "files": [ "RF-C1" ], "subtypes": [ "C-MSI" ] }, { "id": "thyroid", "name": "Thyroid Cancer", "short": "Thyroid", "status": "Partial", "color": "hema", "summary": "Separate exploratory records on thyroid cancer, covering treatment by driver alteration, screening and associations with thyroiditis. These answer distinct questions. Research records only; not personal medical advice.", "axes": [ "Radioactive-iodine-refractory differentiated thyroid cancer — multikinase inhibitors", "RET-altered medullary and papillary thyroid cancer — selective RET inhibitors", "BRAF V600E — anaplastic thyroid cancer and redifferentiation", "NTRK and other fusions — tumour-agnostic inhibitors", "Screening and overdiagnosis — the Korean experience", "Chronic lymphocytic (Hashimoto's) thyroiditis and papillary thyroid cancer — association or detection bias" ], "files": [], "subtypes": [] }, { "id": "gxb", "name": "Gastric × Breast", "short": "G × B", "status": "Active", "color": "hema", "summary": "Targets and pathways that appear in both cancers, compared side by side. The standing question is what extra evidence is needed before a result in one cancer can be carried to the other.", "axes": [ "HER2 agents: where results agree and where they split", "Genomic context of ERBB2 amplification", "HER2 testing rules in each cancer", "PD-1 blockade in both cancers" ], "files": [ "RF-X1" ], "subtypes": [] }, { "id": "expansion", "name": "Expansion Programs", "short": "Expansion", "status": "Planned", "color": "violet", "summary": "Ovarian, endometrial and cervical cancer are follow-on areas. Nothing here is under active analysis yet; the page lists the evidence that would open each programme.", "axes": [ "Ovarian cancer", "Endometrial cancer", "Cervical cancer" ], "files": [], "subtypes": [] } ], "subtypes": [ { "id": "C-MSI", "program": "colorectal", "name": "MSI-H / dMMR (colorectal)", "def": "Study-defined high microsatellite instability or mismatch-repair deficiency. Eligibility criteria, assay and tumor site are recorded with each study; no universal cut-off is assumed, nor any equivalence between colon and rectal settings." }, { "id": "B-HER2POS", "program": "breast", "name": "HER2-positive", "def": "HER2 IHC 3+ or ISH-amplified (IHC 2+/ISH+), regardless of hormone-receptor status." }, { "id": "B-HRPOS", "program": "breast", "name": "HR-positive / HER2-negative", "def": "Oestrogen and/or progesterone receptor positive, HER2 not positive. Includes HER2-0, HER2-ultralow and HER2-low tumours." }, { "id": "B-TNBC", "program": "breast", "name": "Triple-negative", "def": "ER-negative, PR-negative and HER2-negative (NCI definition). Includes HER2-low and HER2-0 tumours." }, { "id": "G-HER2", "program": "gastric", "name": "HER2-positive", "def": "IHC 3+ or IHC 2+ with ISH/FISH amplification, scored with gastric-specific criteria." }, { "id": "G-HER2NEG", "program": "gastric", "name": "HER2-negative", "def": "Not HER2-positive by the gastric criteria." }, { "id": "G-CLDN", "program": "gastric", "name": "CLDN18.2-positive", "def": "Defined by IHC; the threshold differs by study (≥75% moderate-to-strong membranous staining in SPOTLIGHT; ≥2+ in ≥40% of cells in CT041-ST-01)." }, { "id": "G-PDL1", "program": "gastric", "name": "PD-L1 CPS-defined", "def": "Subsets defined by PD-L1 combined positive score cut-offs used in trials (≥1, ≥5). A biomarker subset, not a target." }, { "id": "G-MSI", "program": "gastric", "name": "MSI-H / dMMR", "def": "Microsatellite instability-high or mismatch-repair deficient; a genomic state used to select PD-1 blockade." }, { "id": "G-TCGA", "program": "gastric", "name": "TCGA molecular subtypes", "def": "EBV-positive, microsatellite unstable, genomically stable, chromosomally unstable (TCGA 2014). A research classification, not a treatment-selection rule." } ], "her2Levels": [ { "id": "0", "label": "IHC 0", "sub": "no staining" }, { "id": "ultra", "label": "IHC 0+", "sub": "membrane staining (ultralow)" }, { "id": "1", "label": "IHC 1+", "sub": "" }, { "id": "2neg", "label": "IHC 2+", "sub": "ISH-negative" }, { "id": "2pos", "label": "IHC 2+", "sub": "ISH-positive" }, { "id": "3", "label": "IHC 3+", "sub": "" } ], "her2Matrix": { "HR+": { "0": [ "B-HRPOS", "HER2-0", [] ], "1": [ "B-HRPOS", "HER2-low", [ "U-DB04", "U-DB06" ] ], "3": [ "B-HER2POS", "HER2-positive", [ "U-CLEOPATRA", "U-DB03" ] ], "ultra": [ "B-HRPOS", "HER2-ultralow", [ "U-DB06" ] ], "2neg": [ "B-HRPOS", "HER2-low", [ "U-DB04", "U-DB06" ] ], "2pos": [ "B-HER2POS", "HER2-positive", [ "U-CLEOPATRA", "U-DB03" ] ] }, "HR−": { "0": [ "B-TNBC", "HER2-0", [] ], "1": [ "B-TNBC", "HER2-low", [ "U-DB04" ] ], "3": [ "B-HER2POS", "HER2-positive", [ "U-CLEOPATRA", "U-DB03" ] ], "ultra": [ "B-TNBC", "HER2-ultralow", [] ], "2neg": [ "B-TNBC", "HER2-low", [ "U-DB04" ] ], "2pos": [ "B-HER2POS", "HER2-positive", [ "U-CLEOPATRA", "U-DB03" ] ] } }, "targets": [ { "id": "ERBB2", "name": "HER2", "gene": "ERBB2", "uniprot": "P04626", "cls": "Receptor tyrosine kinase (ERBB family)", "role": "Drug target. HER2 status by IHC/ISH is also the selection biomarker.", "structure": "SD-ERBB2", "pathways": [ "PW-ERBB", "PW-SURFACE" ], "cancers": { "gastric": { "status": "Established target", "text": "Trastuzumab with chemotherapy (ToGA) and trastuzumab deruxtecan (DESTINY-Gastric01, -04) improved survival; zanidatamab improved PFS and OS over trastuzumab (HERIZON-GEA-01). Trials of trastuzumab emtansine, pertuzumab and lapatinib did not meet their primary OS endpoints in the trial-defined efficacy populations; JACOB later reported a descriptive survival signal that does not change its primary result.", "units": [ "U-ToGA", "U-DG01", "U-DG04", "U-KN811", "U-HERIZON", "U-GATSBY", "U-JACOB", "U-LOGiC", "U-TyTAN" ] }, "breast": { "status": "Established target", "text": "Randomised evidence for pertuzumab (CLEOPATRA), trastuzumab emtansine (EMILIA), trastuzumab deruxtecan (DESTINY-Breast03/-04/-06/-09) and tucatinib (HER2CLIMB). Trastuzumab deruxtecan also acts in HER2-low disease.", "units": [ "U-CLEOPATRA", "U-EMILIA", "U-DB03", "U-DB04", "U-DB06", "U-DB09", "U-HER2CLIMB", "U-NCI-BREAST" ] } }, "biomarkers": [ "BM-HER2-G", "BM-HER2-B", "BM-HER2LOW-B", "BM-HER2LOW-G", "BM-pERBB2", "BM-HER2HET", "BM-COAMP" ], "approaches": [ { "cls": "Monoclonal antibody", "agents": "trastuzumab, pertuzumab, margetuximab", "units": [ "U-ToGA", "U-CLEOPATRA", "U-JACOB" ] }, { "cls": "Antibody–drug conjugate", "agents": "trastuzumab emtansine, trastuzumab deruxtecan", "units": [ "U-EMILIA", "U-GATSBY", "U-DB03", "U-DG04" ] }, { "cls": "Tyrosine kinase inhibitor", "agents": "lapatinib, neratinib, tucatinib", "units": [ "U-HER2CLIMB", "U-LOGiC", "U-TyTAN" ] }, { "cls": "Bispecific antibody", "agents": "zanidatamab", "units": [ "U-HERIZON" ] } ], "resistance": [ "RS-HER2LOSS", "RS-COAMP" ], "open": [ "Which gastric tumours lose HER2 after trastuzumab, and does re-testing change second-line comparisons?", "Why did pertuzumab, trastuzumab emtansine and lapatinib fail in gastric trials while trastuzumab and trastuzumab deruxtecan succeeded?", "Can plasma ERBB2 amplification stand in for a new biopsy (64% concordance in DESTINY-Gastric01)?" ], "readiness": { "disease": { "state": "Established", "tone": "good", "note": "Defines treatment subsets in both cancers (NCI PDQ; NCI breast page).", "units": [ "U-NCI-PDQ", "U-NCI-BREAST" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "63 experimental PDB entries on 2026-09-28, including antibody complexes 1N8Z and 1S78; AlphaFold model AF-P04626-F1.", "units": [ "U-HER2Fab", "U-HER2Pert" ] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-DS8201pre16" ] }, "clinical": { "state": "Phase 3 in both cancers", "tone": "good", "note": "Positive and negative phase 3 results in gastric; several positive phase 3 results in breast.", "units": [ "U-ToGA", "U-DG04", "U-CLEOPATRA", "U-DB03" ] }, "limits": { "state": "Documented", "tone": "warn", "note": "HER2 heterogeneity and loss after trastuzumab in gastric cancer. Four gastric/GEJ trials evaluated three agents: trastuzumab emtansine (GATSBY), pertuzumab (JACOB) and lapatinib (LOGiC, TyTAN). Their primary OS endpoints were not met; this does not establish zero effect in every subgroup. JACOB later follow-up is descriptive.", "units": [ "U-GASTHER3", "U-GATSBY", "U-JACOB", "U-LOGiC", "U-TyTAN" ] } }, "protein": { "uniprot": "P04626", "entryName": "ERBB2_HUMAN", "gene": "ERBB2", "name": "Receptor tyrosine-protein kinase erbB-2", "length": 1255, "url": "https://www.uniprot.org/uniprotkb/P04626/entry", "isoforms": [ { "name": "1", "ids": [ "P04626-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P04626-2" ], "status": "Described" }, { "name": "3", "ids": [ "P04626-3" ], "status": "Described" }, { "name": "4", "ids": [ "P04626-4" ], "status": "Described" }, { "name": "5", "ids": [ "P04626-5" ], "status": "Described" }, { "name": "6", "ids": [ "P04626-6" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P04626-F1", "accession": "P04626", "version": 6, "created": "2025-08-01", "mean": 74, "veryHigh": 0.422, "confident": 0.246, "low": 0.086, "veryLow": 0.245, "span": [ 1, 1255 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P04626-F1" }, "experimentalCount": 63, "experimentalLatest": [ "9T3R", "9T3S", "9MTE", "9MTX", "9QBH", "9QBF", "9QBG", "9IUT" ], "evidenceCount": 74 }, { "id": "CLDN18.2", "name": "CLDN18.2", "gene": "CLDN18 (isoform A2)", "uniprot": "P56856", "cls": "Tight-junction membrane protein (claudin family)", "role": "Surface antigen for antibody and CAR-T therapy. CLDN18.2 IHC is the selection biomarker.", "structure": "SD-CLDN18", "pathways": [ "PW-SURFACE" ], "cancers": { "gastric": { "status": "Established target", "text": "In first-line HER2-negative, CLDN18.2-positive, unresectable or metastatic gastric/GEJ adenocarcinoma, zolbetuximab improved PFS and OS with mFOLFOX6 (SPOTLIGHT) or CAPOX (GLOW), each versus placebo plus the same chemotherapy, and is listed in NCI PDQ. The separate randomized phase 2 CT041-ST-01 trial found a PFS benefit for satri-cel versus physician’s choice after at least two prior treatment lines; its CLDN18.2 selection threshold differed.", "units": [ "U-SPOTLIGHT", "U-GLOW", "U-CT041", "U-NCI-PDQ" ] }, "breast": { "status": "No evidence in library", "text": "No CLDN18.2 study in breast cancer has been curated.", "units": [] } }, "biomarkers": [ "BM-CLDN18" ], "approaches": [ { "cls": "Monoclonal antibody", "agents": "zolbetuximab (osemitamab appears only as a PDB complex)", "units": [ "U-SPOTLIGHT", "U-GLOW" ] }, { "cls": "CAR T cells", "agents": "satricabtagene autoleucel (satri-cel)", "units": [ "U-CT041" ] } ], "resistance": [], "open": [ "Do the two IHC thresholds (≥75% moderate-to-strong vs ≥2+ in ≥40%) select different patients?", "Where is the zolbetuximab epitope relative to the isoform-specific residues 1–69 (A3)?", "Does CLDN18.2 expression change after antibody or CAR-T therapy?" ], "readiness": { "disease": { "state": "Established in gastric", "tone": "good", "note": "Selects first-line therapy in NCI PDQ.", "units": [ "U-NCI-PDQ" ] }, "structure": { "state": "Experimental (2026) and predicted", "tone": "partial", "note": "Three cryo-EM complexes released 2026-05-27 (9V32 with zolbetuximab Fab, 4.1 Å); isoform-specific AlphaFold model AF-P56856-2-F1. No primary citation yet for the cryo-EM entries.", "units": [ "U-A3" ] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-ZOLpre24" ] }, "clinical": { "state": "Phase 3 (gastric)", "tone": "good", "note": "Two positive phase 3 trials; one randomised phase 2 of CAR T cells.", "units": [ "U-SPOTLIGHT", "U-GLOW", "U-CT041" ] }, "limits": { "state": "Threshold not harmonised", "tone": "warn", "note": "SPOTLIGHT required ≥75% of tumour cells with moderate-to-strong membranous staining; CT041-ST-01 used IHC ≥2+ in ≥40%. These thresholds and treatment settings are not interchangeable. SPOTLIGHT’s GEJ subgroup was too small for a separate benefit conclusion. Zolbetuximab nausea/vomiting affected exposure or early discontinuation; maintained measured quality of life does not establish absence of harm, and exploratory post-randomization censoring does not establish causal survival benefit. Cytokine release syndrome was common among satri-cel recipients in CT041-ST-01.", "units": [ "U-SPOTLIGHT", "U-CT041" ] } }, "protein": { "uniprot": "P56856", "entryName": "CLD18_HUMAN", "gene": "CLDN18", "name": "Claudin-18", "length": 261, "url": "https://www.uniprot.org/uniprotkb/P56856/entry", "isoforms": [ { "name": "A1", "ids": [ "P56856-1" ], "status": "Displayed" }, { "name": "A2", "ids": [ "P56856-2" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P56856-F1", "accession": "P56856", "version": 6, "created": "2025-08-01", "mean": 72.81, "veryHigh": 0.314, "confident": 0.28, "low": 0.199, "veryLow": 0.207, "span": [ 1, 261 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P56856-F1" }, "experimentalCount": 3, "experimentalLatest": [ "9V2U", "9V31", "9V32" ], "evidenceCount": 5 }, { "id": "ESR1", "name": "ERα", "gene": "ESR1", "uniprot": "P03372", "cls": "Nuclear hormone receptor", "role": "Drug target of endocrine therapy. ESR1 mutation is a selection biomarker for newer ER antagonists and degraders.", "structure": "SD-ESR1", "pathways": [ "PW-ER" ], "cancers": { "breast": { "status": "Established target", "text": "In previously treated ER-positive/HER2-negative advanced disease, elacestrant improved PFS overall and in ESR1-mutated patients (EMERALD). Imlunestrant and vepdegestrant monotherapy showed significant PFS benefit in ESR1-mutated populations, without a significant difference overall (EMBER-3, VERITAC-2). The separate EMBER-3 comparison favored imlunestrant plus abemaciclib over imlunestrant alone. Before progression at blood ESR1-mutation emergence, switching to intramuscular fulvestrant with continued palbociclib (PADA-1) or oral camizestrant with continued CDK4/6 inhibition (SERENA-6) improved PFS.", "units": [ "U-EMERALD", "U-EMBER3", "U-VERITAC2", "U-PADA1", "U-SERENA6" ] }, "gastric": { "status": "Not studied here", "text": "Not a target studied in gastric cancer in this library.", "units": [] } }, "biomarkers": [ "BM-ESR1", "BM-HR" ], "approaches": [ { "cls": "Oral SERD / ER antagonist", "agents": "elacestrant, camizestrant, imlunestrant", "units": [ "U-EMERALD", "U-SERENA6", "U-EMBER3" ] }, { "cls": "PROTAC ER degrader", "agents": "vepdegestrant", "units": [ "U-VERITAC2" ] } ], "resistance": [ "RS-ESR1", "RS-MAPK" ], "open": [ "Does switching at ESR1 emergence improve overall survival or only PFS?", "Which ESR1 variants (D538G, Y537S, E380Q…) respond differently to each degrader?", "How often do ESR1 subclones coexist with MAPK or ER-machinery alterations?" ], "readiness": { "disease": { "state": "Established in HR+ breast", "tone": "good", "note": "Endocrine therapy is the backbone of HR+ disease; ESR1 mutations enrich after treatment (A2).", "units": [ "U-A2", "U-Razavi18" ] }, "structure": { "state": "Extensive experimental and predicted", "tone": "good", "note": "493 experimental entries, 131 mentioning Y537S (2026-09-28); AlphaFold model has 46.4% very-low-confidence residues.", "units": [ "U-ERago", "U-ERtam" ] }, "function": { "state": "Preclinical mechanism", "tone": "partial", "note": "Y537S and D538G stabilise the AF-2 binding conformation (Fanning 2016).", "units": [ "U-Fanning16" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Phase 3 trials distinguish molecularly triggered switching before progression (PADA-1, SERENA-6) from new degraders after prior endocrine therapy (EMERALD, EMBER-3, VERITAC-2).", "units": [ "U-PADA1", "U-SERENA6", "U-EMERALD", "U-EMBER3", "U-VERITAC2" ] }, "limits": { "state": "Subgroup-dependent", "tone": "warn", "note": "PFS findings depend on mutation status, regimen and comparator: EMERALD was positive overall and in ESR1-mutated patients; EMBER-3 and VERITAC-2 monotherapy comparisons were significant in ESR1-mutated populations but not overall. These PFS results do not by themselves establish overall-survival benefit.", "units": [ "U-EMBER3", "U-VERITAC2", "U-EMERALD" ] } }, "protein": { "uniprot": "P03372", "entryName": "ESR1_HUMAN", "gene": "ESR1", "name": "Estrogen receptor", "length": 595, "url": "https://www.uniprot.org/uniprotkb/P03372/entry", "isoforms": [ { "name": "1", "ids": [ "P03372-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P03372-2" ], "status": "Described" }, { "name": "3", "ids": [ "P03372-3" ], "status": "Described" }, { "name": "4", "ids": [ "P03372-4" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P03372-F1", "accession": "P03372", "version": 6, "created": "2025-08-01", "mean": 66.44, "veryHigh": 0.435, "confident": 0.069, "low": 0.032, "veryLow": 0.464, "span": [ 1, 595 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P03372-F1" }, "experimentalCount": 493, "experimentalLatest": [ "11ZU", "9YC4", "11SD", "11SE", "11SF", "11SG", "11SH", "11SI" ], "evidenceCount": 15 }, { "id": "PIK3CA", "name": "PI3Kα", "gene": "PIK3CA", "uniprot": "P42336", "cls": "Lipid kinase catalytic subunit p110α", "role": "Drug target. PIK3CA mutation selects patients.", "structure": "SD-PIK3CA", "pathways": [ "PW-PI3K", "PW-ERBB" ], "cancers": { "breast": { "status": "Established target", "text": "Alpelisib plus fulvestrant after prior endocrine therapy improved PFS in PIK3CA-mutated HR+/HER2− advanced breast cancer (SOLAR-1); first-line inavolisib plus palbociclib-fulvestrant versus placebo plus palbociclib-fulvestrant after relapse during or within 12 months after completion of adjuvant endocrine therapy improved PFS with final OS benefit (INAVO120); RLY-2608, a mutant-selective allosteric inhibitor, is in phase 3.", "units": [ "U-SOLAR1", "U-INAVO120", "U-RLY2608" ] }, "gastric": { "status": "Biology only", "text": "TCGA reports recurrent PIK3CA mutations in EBV-positive gastric cancer; no PI3Kα trial in the library.", "units": [ "U-TCGASTAD" ] } }, "biomarkers": [ "BM-PI3K" ], "approaches": [ { "cls": "PI3Kα inhibitor", "agents": "alpelisib, inavolisib", "units": [ "U-SOLAR1", "U-INAVO120" ] }, { "cls": "Mutant-selective allosteric inhibitor", "agents": "RLY-2608 (investigational)", "units": [ "U-RLY2608" ] } ], "resistance": [], "open": [ "Does mutant selectivity remove the hyperglycaemia seen with alpelisib in patients?", "How do PIK3CA-mutant tumours respond to PI3Kα vs AKT inhibition head to head (NCT06982521)?" ], "readiness": { "disease": { "state": "Established in HR+ breast", "tone": "good", "note": "PIK3CA mutated in 41–44% of HR+/HER2− samples (A2).", "units": [ "U-A2" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "138 experimental entries; AlphaFold mean pLDDT 92.4 for p110α alone (no p85α).", "units": [ "U-BYL719" ] }, "function": { "state": "Preclinical allosteric mechanism", "tone": "partial", "note": "MD simulation and cryo-EM of mutant activation (RLY-2608 paper).", "units": [ "U-RLY2608" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "SOLAR-1 demonstrated PFS benefit after prior endocrine therapy. INAVO120 demonstrated PFS and formal final OS benefit with first-line inavolisib plus palbociclib-fulvestrant versus placebo plus the same backbone in the selected early endocrine-relapse population.", "units": [ "U-SOLAR1", "U-INAVO120" ] }, "limits": { "state": "Toxicity documented", "tone": "warn", "note": "Grade 3–4 hyperglycaemia occurred in 36.6% with alpelisib in SOLAR-1. In INAVO120, hyperglycaemia, stomatitis/mucosal inflammation, gastrointestinal and ocular harms were more frequent with inavolisib than placebo on the same backbone. Benefit was demonstrated in selected early endocrine relapse, not all later-line or CDK4/6-resistant disease; these trials do not establish comparative safety between PI3K inhibitors.", "units": [ "U-SOLAR1", "U-INAVO120" ] } }, "protein": { "uniprot": "P42336", "entryName": "PK3CA_HUMAN", "gene": "PIK3CA", "name": "Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform", "length": 1068, "url": "https://www.uniprot.org/uniprotkb/P42336/entry", "isoforms": [] }, "predicted": { "entryId": "AF-P42336-F1", "accession": "P42336", "version": 6, "created": "2025-08-01", "mean": 92.38, "veryHigh": 0.822, "confident": 0.117, "low": 0.05, "veryLow": 0.011, "span": [ 1, 1068 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P42336-F1" }, "experimentalCount": 139, "experimentalLatest": [ "9YF2", "9XW5", "9XW7", "9XW8", "9NI3", "9NI8", "9NI7", "9NIF" ], "evidenceCount": 6 }, { "id": "AKT", "name": "AKT", "gene": "AKT1 (AlphaFold entry shown for AKT1)", "uniprot": "P31749", "cls": "Serine/threonine kinase", "role": "Drug target of capivasertib.", "structure": null, "pathways": [ "PW-PI3K" ], "cancers": { "breast": { "status": "Established target", "text": "Capivasertib plus fulvestrant improved PFS overall and in AKT pathway-altered tumours (CAPItello-291).", "units": [ "U-CAP291", "U-NCI-BREAST" ] } }, "biomarkers": [ "BM-PI3K" ], "approaches": [ { "cls": "AKT inhibitor", "agents": "capivasertib", "units": [ "U-CAP291" ] } ], "resistance": [], "open": [ "Is the AKT pathway alteration a selection biomarker, given benefit in the overall population?" ], "readiness": { "disease": { "state": "Supported", "tone": "partial", "note": "AKT pathway alterations in 40.8% of CAPItello-291.", "units": [ "U-CAP291" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "56 experimental entries for AKT1.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-AZD5363pre12" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Phase 3 PFS benefit; final OS not significant in the 2026 congress abstract.", "units": [ "U-CAP291" ] }, "limits": { "state": "Biomarker role unsettled", "tone": "warn", "note": "PFS benefit in the overall and altered populations does not establish benefit in every individual biomarker subgroup. Final OS was not significantly improved in the 2026 congress abstract.", "units": [ "U-CAP291" ] } }, "protein": { "uniprot": "P31749", "entryName": "AKT1_HUMAN", "gene": "AKT1", "name": "RAC-alpha serine/threonine-protein kinase", "length": 480, "url": "https://www.uniprot.org/uniprotkb/P31749/entry", "isoforms": [ { "name": "1", "ids": [ "P31749-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P31749-2" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P31749-F1", "accession": "P31749", "version": 6, "created": "2025-08-01", "mean": 83.06, "veryHigh": 0.537, "confident": 0.296, "low": 0.067, "veryLow": 0.1, "span": [ 1, 480 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P31749-F1" }, "experimentalCount": 56, "experimentalLatest": [ "9TMT", "9TMU", "9TMV", "9TMW", "9TMY", "9TMZ", "9TN0", "9TN1" ], "evidenceCount": 2 }, { "id": "CDK4/6", "name": "CDK4/6", "gene": "CDK4, CDK6", "uniprot": "P11802", "cls": "Cell-cycle kinases", "role": "Drug targets of abemaciclib, palbociclib and ribociclib.", "structure": null, "pathways": [ "PW-ER" ], "cancers": { "breast": { "status": "Established target (advanced); conflicting (adjuvant)", "text": "Listed by NCI for HR-positive breast cancer. Adjuvant results differ: monarchE showed IDFS and formal OS benefit for abemaciclib in high-risk node-positive HR+/HER2-negative disease; NATALEE showed iDFS benefit for ribociclib in selected stage II/III including high-risk node-negative disease, with OS still maturing and no established OS benefit; palbociclib did not improve IDFS (PALLAS, PENELOPE-B).", "units": [ "U-monarchE", "U-NATALEE", "U-PALLAS", "U-PENELOPEB", "U-NCI-BREAST" ] } }, "biomarkers": [ "BM-HR" ], "approaches": [ { "cls": "CDK4/6 inhibitor", "agents": "abemaciclib, palbociclib, ribociclib", "units": [ "U-monarchE", "U-NATALEE", "U-PALLAS" ] } ], "resistance": [], "open": [ "Why did adjuvant palbociclib fail when abemaciclib and ribociclib succeeded?" ], "readiness": { "disease": { "state": "Established in HR+ breast", "tone": "good", "note": "NCI breast page.", "units": [ "U-NCI-BREAST" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "15 (CDK4) and 22 (CDK6) experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-PD0332991pre09" ] }, "clinical": { "state": "Phase 3, conflicting in adjuvant", "tone": "warn", "note": "monarchE: IDFS and formal OS benefit in high-risk node-positive HR+/HER2-negative disease; NATALEE: iDFS benefit in selected stage II/III with OS maturing, no established OS benefit; PALLAS and PENELOPE-B: no palbociclib IDFS improvement.", "units": [ "U-monarchE", "U-NATALEE", "U-PALLAS", "U-PENELOPEB" ] }, "limits": { "state": "Class effect not uniform", "tone": "warn", "note": "Adjuvant benefit differs by agent or design.", "units": [ "U-PENELOPEB" ] } }, "protein": { "uniprot": "P11802", "entryName": "CDK4_HUMAN", "gene": "CDK4", "name": "Cyclin-dependent kinase 4", "length": 303, "url": "https://www.uniprot.org/uniprotkb/P11802/entry", "isoforms": [ { "name": "1", "ids": [ "P11802-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P11802-2" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P11802-F1", "accession": "P11802", "version": 6, "created": "2025-08-01", "mean": 86.81, "veryHigh": 0.67, "confident": 0.185, "low": 0.076, "veryLow": 0.069, "span": [ 1, 303 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P11802-F1" }, "experimentalCount": 15, "experimentalLatest": [ "9CSK", "7SJ3", "6P8E", "6P8F", "6P8G", "6P8H", "5FWP", "5FWK" ], "evidenceCount": 25 }, { "id": "TACSTD2", "name": "TROP2", "gene": "TACSTD2", "uniprot": "P09758", "cls": "Cell-surface glycoprotein", "role": "Target antigen for antibody–drug conjugates. In TROPiCS-02, expression level did not identify which patients benefited.", "structure": null, "pathways": [ "PW-SURFACE" ], "cancers": { "breast": { "status": "Established target", "text": "Sacituzumab govitecan improved OS in pretreated metastatic TNBC (ASCENT) and pretreated HR+/HER2− disease (TROPiCS-02). Datopotamab deruxtecan improved PFS in pretreated HR+/HER2− disease, but final OS was not significantly improved (TROPION-Breast01). In previously untreated advanced TNBC, sacituzumab govitecan plus pembrolizumab improved PFS in PD-L1-positive disease, versus chemotherapy plus pembrolizumab, with immature OS (ASCENT-04). In untreated advanced TNBC for whom immunotherapy was not an option, sacituzumab govitecan improved PFS with OS not reported in the primary abstract (ASCENT-03), while datopotamab deruxtecan improved both dual primary endpoints of PFS and OS (TROPION-Breast02).", "units": [ "U-ASCENT", "U-TROPiCS02", "U-TROPIONB01", "U-ASCENT04", "U-ASCENT03", "U-TROPIONB02" ] } }, "biomarkers": [ "BM-TROP2" ], "approaches": [ { "cls": "Antibody–drug conjugate", "agents": "sacituzumab govitecan, datopotamab deruxtecan", "units": [ "U-ASCENT", "U-TROPiCS02", "U-TROPIONB01", "U-ASCENT04", "U-ASCENT03", "U-TROPIONB02" ] } ], "resistance": [], "open": [ "What happens when one ADC follows another (TROP2 after HER2, or the reverse)? Existing retrospective cohorts do not establish optimal sequence or randomised comparison." ], "readiness": { "disease": { "state": "Supported", "tone": "partial", "note": "Target antigen; not a selection biomarker in TROPiCS-02.", "units": [ "U-TROPiCS02" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "7 experimental entries, including sacituzumab Fab–TROP2 (9PI9).", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-SGpre15" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Phase 3 findings depend on setting and endpoint: OS benefits in ASCENT, TROPiCS-02 and TROPION-Breast02; PFS benefit without significant final OS improvement in TROPION-Breast01; PFS benefits with OS immature in ASCENT-04 or not reported in the primary ASCENT-03 abstract. Immunotherapy-not-option populations are not synonymous with PD-L1-negative disease.", "units": [ "U-ASCENT", "U-TROPiCS02", "U-TROPIONB01", "U-ASCENT04", "U-ASCENT03", "U-TROPIONB02" ] }, "limits": { "state": "Sequencing unknown", "tone": "open", "note": "Existing retrospective ADC sequence cohorts do not establish optimal sequence or randomised comparison.", "units": [ "U-ADCLow", "U-ADCSequence84" ] } }, "protein": { "uniprot": "P09758", "entryName": "TACD2_HUMAN", "gene": "TACSTD2", "name": "Tumor-associated calcium signal transducer 2", "length": 323, "url": "https://www.uniprot.org/uniprotkb/P09758/entry", "isoforms": [] }, "predicted": { "entryId": "AF-P09758-F1", "accession": "P09758", "version": 6, "created": "2025-08-01", "mean": 82.69, "veryHigh": 0.594, "confident": 0.155, "low": 0.164, "veryLow": 0.087, "span": [ 1, 323 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P09758-F1" }, "experimentalCount": 7, "experimentalLatest": [ "9PI9", "7E5M", "7E5N", "7PEE", "2MVK", "2MVL", "2MAE" ], "evidenceCount": 9 }, { "id": "PDCD1", "name": "PD-1", "gene": "PDCD1", "uniprot": "Q15116", "cls": "Immune checkpoint receptor on T cells", "role": "Drug target of pembrolizumab, nivolumab and tislelizumab. PD-L1 expression and MSI-H/dMMR are selection biomarkers, not targets.", "structure": null, "pathways": [ "PW-IMMUNE" ], "cancers": { "gastric": { "status": "Established target", "text": "First-line benefit with nivolumab (CheckMate 649), pembrolizumab (KEYNOTE-859) and tislelizumab (RATIONALE-305); second-line pembrolizumab failed (KEYNOTE-061); first-line monotherapy was not superior (KEYNOTE-062).", "units": [ "U-CM649", "U-KN859", "U-RAT305", "U-KN061", "U-KN062", "U-KN811" ] }, "breast": { "status": "Established target (TNBC)", "text": "In untreated stage II/III TNBC, KEYNOTE-522 improved pCR with preoperative pembrolizumab plus chemotherapy. The full perioperative strategy, including postoperative pembrolizumab, improved EFS and final overall survival versus matched chemotherapy/placebo control; the trial cannot isolate each treatment phase’s survival contribution.", "units": [ "U-KN522" ] } }, "biomarkers": [ "BM-PDL1-CPS", "BM-PDL1-TAP", "BM-MSI", "BM-EBV" ], "approaches": [ { "cls": "Anti-PD-1 antibody", "agents": "pembrolizumab, nivolumab, tislelizumab", "units": [ "U-CM649", "U-KN859", "U-RAT305" ] } ], "resistance": [], "open": [ "Are CPS and TAP cut-offs interchangeable across antibodies?", "Why did second-line pembrolizumab fail in CPS ≥ 1 gastric cancer?" ], "readiness": { "disease": { "state": "Established", "tone": "good", "note": "NCI PDQ lists PD-1 blockade.", "units": [ "U-NCI-PDQ" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "38 experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-PD1Rupp22" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Positive and negative phase 3 results.", "units": [ "U-CM649", "U-KN061" ] }, "limits": { "state": "Biomarker-dependent", "tone": "warn", "note": "Benefit varies with PD-L1 level and assay.", "units": [ "U-KN062" ] } }, "protein": { "uniprot": "Q15116", "entryName": "PDCD1_HUMAN", "gene": "PDCD1", "name": "Programmed cell death protein 1", "length": 288, "url": "https://www.uniprot.org/uniprotkb/Q15116/entry", "isoforms": [] }, "predicted": { "entryId": "AF-Q15116-F1", "accession": "Q15116", "version": 6, "created": "2025-08-01", "mean": 74.12, "veryHigh": 0.358, "confident": 0.212, "low": 0.267, "veryLow": 0.163, "span": [ 1, 288 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-Q15116-F1" }, "experimentalCount": 38, "experimentalLatest": [ "9W43", "9EHT", "9Q8L", "9HK1", "8U31", "8U32", "8EQ6", "8GY5" ], "evidenceCount": 34 }, { "id": "CD274", "name": "PD-L1", "gene": "CD274", "uniprot": "Q9NZQ7", "cls": "Immune checkpoint ligand", "role": "Drug target of atezolizumab, durvalumab and avelumab. PD-L1 expression is also used as a biomarker, measured differently by each assay.", "structure": null, "pathways": [ "PW-IMMUNE" ], "cancers": { "breast": { "status": "Conflicting", "text": "In advanced TNBC, atezolizumab with nab-paclitaxel improved PFS (IMpassion130), whereas with paclitaxel it did not in PD-L1-positive disease (IMpassion131). In surgery-first adjuvant TNBC, adding atezolizumab to chemotherapy did not improve invasive disease-free survival (IMpassion030).", "units": [ "U-IMP130", "U-IMP131", "U-IMP030" ] }, "gastric": { "status": "Mixed", "text": "PD-L1 is also used as a selection biomarker (CPS, TAP). In resectable disease, perioperative durvalumab plus FLOT improved EFS with formal final OS improvement; the comparison reflects the complete perioperative strategy, not isolated phases. After induction chemotherapy for unresectable disease, avelumab switch maintenance did not show OS superiority.", "units": [ "U-CM649", "U-RAT305", "U-MATTERHORN", "U-JAVG100" ] } }, "biomarkers": [ "BM-PDL1-B", "BM-PDL1-CPS" ], "approaches": [ { "cls": "Anti-PD-L1 antibody", "agents": "atezolizumab", "units": [ "U-IMP130", "U-IMP131" ] }, { "cls": "Anti-PD-L1 antibody", "agents": "durvalumab", "units": [ "U-MATTERHORN" ] }, { "cls": "Anti-PD-L1 antibody", "agents": "avelumab", "units": [ "U-JAVG100" ] } ], "resistance": [], "open": [ "Does the companion chemotherapy explain the IMpassion130/131 split?" ], "readiness": { "disease": { "state": "Supported", "tone": "partial", "note": "TCGA reports CD274 amplification in EBV-positive gastric cancer.", "units": [ "U-TCGASTAD" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "78 experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-PDL1Glyco16" ] }, "clinical": { "state": "Conflicting", "tone": "warn", "note": "Conflicting phase 3 results in TNBC: atezolizumab with nab-paclitaxel improved PFS in advanced disease (IMpassion130) but with paclitaxel did not in PD-L1-positive disease (IMpassion131), and adjuvant atezolizumab did not improve invasive disease-free survival in surgery-first disease (IMpassion030).", "units": [ "U-IMP130", "U-IMP131", "U-IMP030" ] }, "limits": { "state": "Assay and design", "tone": "warn", "note": "Cross-trial comparisons cannot isolate companion chemotherapy or treatment timing as causal explanations for differing results. In IMpassion030, nonsignificant invasive disease-free survival does not establish equivalence or confirmed harm.", "units": [] } }, "protein": { "uniprot": "Q9NZQ7", "entryName": "PD1L1_HUMAN", "gene": "CD274", "name": "Programmed cell death 1 ligand 1", "length": 290, "url": "https://www.uniprot.org/uniprotkb/Q9NZQ7/entry", "isoforms": [ { "name": "1", "ids": [ "Q9NZQ7-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "Q9NZQ7-2" ], "status": "Described" }, { "name": "3", "ids": [ "Q9NZQ7-3" ], "status": "Described" }, { "name": "4", "ids": [ "Q9NZQ7-4" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-Q9NZQ7-F1", "accession": "Q9NZQ7", "version": 6, "created": "2025-08-01", "mean": 88.25, "veryHigh": 0.71, "confident": 0.134, "low": 0.138, "veryLow": 0.017, "span": [ 1, 290 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-Q9NZQ7-F1" }, "experimentalCount": 80, "experimentalLatest": [ "13DS", "13DT", "35TL", "9TZM", "9KSB", "13FL", "9QSM", "9MAP" ], "evidenceCount": 12 }, { "id": "KDR", "name": "VEGFR2", "gene": "KDR", "uniprot": "P35968", "cls": "Receptor tyrosine kinase (angiogenesis)", "role": "Drug target of ramucirumab.", "structure": null, "pathways": [ "PW-VEGF" ], "cancers": { "gastric": { "status": "Established (later lines)", "text": "Ramucirumab improved OS in second-line RAINBOW and REGARD. First-line RAINFALL improved investigator-assessed PFS, without corroboration by central review or a statistically significant OS improvement. After progression on ramucirumab, third-or-later-line RINDBeRG found improved PFS but no statistically significant OS advantage for ramucirumab plus irinotecan over irinotecan alone.", "units": [ "U-RAINBOW", "U-REGARD", "U-RAINFALL", "U-NCI-PDQ", "U-RINDBeRG" ] } }, "biomarkers": [], "approaches": [ { "cls": "Anti-VEGFR2 antibody", "agents": "ramucirumab", "units": [ "U-RAINBOW", "U-REGARD" ] } ], "resistance": [], "open": [ "No selection biomarker is curated for ramucirumab." ], "readiness": { "disease": { "state": "Supported", "tone": "partial", "note": "Angiogenesis target without a selection biomarker.", "units": [] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "54 experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-VEGFR2Mashima21" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Second-line OS benefit in RAINBOW and REGARD. RAINFALL PFS findings differed by assessor, with nonsignificant OS; RINDBeRG improved PFS but did not meet its primary OS endpoint after prior ramucirumab progression.", "units": [ "U-RAINBOW", "U-REGARD", "U-RAINFALL", "U-RINDBeRG" ] }, "limits": { "state": "Line-dependent", "tone": "warn", "note": "Benefits depend on setting and endpoint. Nonsignificant OS does not establish equivalence or zero effect. RAINFALL PFS differed by assessor; RINDBeRG source discrepancies in hazard ratios and P values remain unresolved in the linked unit.", "units": [ "U-RAINFALL", "U-RINDBeRG" ] } }, "protein": { "uniprot": "P35968", "entryName": "VGFR2_HUMAN", "gene": "KDR", "name": "Vascular endothelial growth factor receptor 2", "length": 1356, "url": "https://www.uniprot.org/uniprotkb/P35968/entry", "isoforms": [ { "name": "1", "ids": [ "P35968-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P35968-2" ], "status": "Described" }, { "name": "3", "ids": [ "P35968-3" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P35968-F1", "accession": "P35968", "version": 6, "created": "2025-08-01", "mean": 71.12, "veryHigh": 0.235, "confident": 0.434, "low": 0.076, "veryLow": 0.255, "span": [ 1, 1356 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P35968-F1" }, "experimentalCount": 54, "experimentalLatest": [ "6XVJ", "6XVK", "6GQO", "6GQP", "6GQQ", "5OYJ", "5EW3", "3WZD" ], "evidenceCount": 8 }, { "id": "PARP1", "name": "PARP1/2", "gene": "PARP1 (AlphaFold entry shown for PARP1)", "uniprot": "P09874", "cls": "DNA repair enzymes", "role": "Drug target of olaparib and talazoparib. Germline BRCA1/2 mutation is the selection biomarker.", "structure": null, "pathways": [ "PW-DDR" ], "cancers": { "breast": { "status": "Established (BRCA-mutated)", "text": "In germline BRCA-mutated, HER2-negative, high-risk early breast cancer after local therapy and (neo)adjuvant chemotherapy, adjuvant olaparib improved IDFS and met formal OS significance at the prespecified second interim analysis (OlympiA), with descriptive longer follow-up showing sustained benefit. In metastatic disease, olaparib (OlympiAD) and talazoparib (EMBRACA) improved PFS over chemotherapy, but final OS differences were not statistically significant. NCI lists olaparib and talazoparib.", "units": [ "U-OlympiA", "U-NCI-BREAST", "U-EMBRACA", "U-OlympiAD" ] } }, "biomarkers": [ "BM-gBRCA" ], "approaches": [ { "cls": "PARP inhibitor", "agents": "olaparib, talazoparib", "units": [ "U-OlympiA" ] } ], "resistance": [], "open": [ "How large is the overlap between gBRCA carriers and the clinical high-risk groups of CDK4/6 adjuvant trials?" ], "readiness": { "disease": { "state": "Established (gBRCA)", "tone": "good", "note": "Restricted to BRCA-mutated disease.", "units": [ "U-OlympiA" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "106 experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-PARPRottenberg08" ] }, "clinical": { "state": "Phase 3", "tone": "good", "note": "Phase 3 evidence in germline BRCA-mutated, HER2-negative breast cancer: high-risk early-disease adjuvant trial (OlympiA) demonstrating IDFS benefit and formal OS significance at the prespecified second interim analysis alongside descriptive longer follow-up; metastatic trials (OlympiAD, EMBRACA) demonstrating PFS improvements over chemotherapy, but nonsignificant final OS.", "units": [ "U-OlympiA", "U-EMBRACA", "U-OlympiAD" ] }, "limits": { "state": "Narrow population", "tone": "open", "note": "Restricted to germline BRCA1/2-mutated, HER2-negative breast cancer; findings cannot be extrapolated to somatic-only mutations, broader HRD populations, or unselected breast cancer. In metastatic disease, demonstrated PFS benefit cannot be equated to established OS benefit, though nonsignificant final OS does not prove absence of survival effect. Established PARP inhibitor toxicities and long-term safety require continued monitoring.", "units": [ "U-OlympiA", "U-EMBRACA", "U-OlympiAD" ] } }, "protein": { "uniprot": "P09874", "entryName": "PARP1_HUMAN", "gene": "PARP1", "name": "Poly [ADP-ribose] polymerase 1", "length": 1014, "url": "https://www.uniprot.org/uniprotkb/P09874/entry", "isoforms": [] }, "predicted": { "entryId": "AF-P09874-F1", "accession": "P09874", "version": 6, "created": "2025-08-01", "mean": 82.38, "veryHigh": 0.495, "confident": 0.333, "low": 0.061, "veryLow": 0.11, "span": [ 1, 1014 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P09874-F1" }, "experimentalCount": 106, "experimentalLatest": [ "9UMC", "9UMF", "9MI8", "9MJA", "8VYH", "9ILN", "9BPY", "9DMC" ], "evidenceCount": 4 }, { "id": "FGFR2", "name": "FGFR2", "gene": "FGFR2", "uniprot": "P21802", "cls": "Receptor tyrosine kinase", "role": "Investigational FGFR2b-directed antibody target with randomized phase 2 and phase 3 evidence in selected gastric/gastroesophageal junction adenocarcinoma.", "structure": null, "pathways": [ "PW-ERBB" ], "cancers": { "gastric": { "status": "Candidate", "text": "FGFR2 amplification in 19/438 TCGA gastric tumours (4.3%) and in 4 of 58 ERBB2-amplified tumours (A1). Amplification is not interchangeable with FGFR2b IHC selection. FIGHT provides exploratory phase 2 evidence. FORTITUDE-101 met its primary interim OS boundary in the prespecified >=10% staining population, with attenuated estimates on later descriptive follow-up; the reviewed source is a conference abstract.", "units": [ "U-A1", "U-FIGHT", "U-FORT101" ] } }, "biomarkers": [ "BM-COAMP" ], "approaches": [ { "cls": "FGFR2b-directed antibody", "agents": "bemarituzumab with mFOLFOX6 (investigational)", "units": [ "U-FIGHT", "U-FORT101" ] } ], "resistance": [ "RS-COAMP" ], "open": [ "How do full FORTITUDE-101 results and eligibility/amendment history clarify the interim and later descriptive findings?", "How should corneal risk and biomarker selection be evaluated in further research?" ], "readiness": { "disease": { "state": "Emerging", "tone": "open", "note": "Amplified subset in TCGA gastric (A1).", "units": [ "U-A1" ] }, "structure": { "state": "Experimental and predicted", "tone": "good", "note": "65 experimental entries.", "units": [] }, "function": { "state": "Preclinical, one study", "tone": "partial", "note": "One preclinical study in the library, added by Codex (GPT-6) on 2026-09-28. Read the unit for the model and its limits; a model result is not a clinical finding.", "units": [ "U-FGFR2Xie13" ] }, "clinical": { "state": "Phase 2 / 3 evidence", "tone": "partial", "note": "FIGHT is exploratory phase 2 evidence; its primary report, SAP testing threshold and final descriptive analysis require separate interpretation. FORTITUDE-101 reports interim OS success with attenuation at later descriptive follow-up in the prespecified >=10% IHC population.", "units": [ "U-FIGHT", "U-FORT101" ] }, "limits": { "state": "Limited", "tone": "partial", "note": "FGFR2 amplification is not interchangeable with FGFR2b IHC selection. FIGHT subgroup findings are exploratory. FORTITUDE-101 is conference-abstract evidence with unresolved eligibility/amendment detail; later descriptive follow-up does not constitute a new formal failure test. Corneal adverse events are a material safety signal. These sources do not establish efficacy with contemporary chemoimmunotherapy.", "units": [ "U-FIGHT", "U-FORT101" ] } }, "protein": { "uniprot": "P21802", "entryName": "FGFR2_HUMAN", "gene": "FGFR2", "name": "Fibroblast growth factor receptor 2", "length": 821, "url": "https://www.uniprot.org/uniprotkb/P21802/entry", "isoforms": [ { "name": "1", "ids": [ "P21802-1" ], "status": "Displayed" }, { "name": "2", "ids": [ "P21802-2" ], "status": "Described" }, { "name": "3", "ids": [ "P21802-3" ], "status": "Described" }, { "name": "4", "ids": [ "P21802-4" ], "status": "Described" }, { "name": "5", "ids": [ "P21802-5" ], "status": "Described" }, { "name": "6", "ids": [ "P21802-6" ], "status": "Described" }, { "name": "7", "ids": [ "P21802-8" ], "status": "Described" }, { "name": "8", "ids": [ "P21802-14" ], "status": "Described" }, { "name": "9", "ids": [ "P21802-15" ], "status": "Described" }, { "name": "10", "ids": [ "P21802-16" ], "status": "Described" }, { "name": "11", "ids": [ "P21802-17" ], "status": "Described" }, { "name": "12", "ids": [ "P21802-18" ], "status": "Described" }, { "name": "13", "ids": [ "P21802-19" ], "status": "Described" }, { "name": "14", "ids": [ "P21802-20" ], "status": "Described" }, { "name": "15", "ids": [ "P21802-21" ], "status": "Described" }, { "name": "16", "ids": [ "P21802-22" ], "status": "Described" }, { "name": "17", "ids": [ "P21802-23" ], "status": "Described" } ] }, "predicted": { "entryId": "AF-P21802-F1", "accession": "P21802", "version": 6, "created": "2025-08-01", "mean": 73.94, "veryHigh": 0.367, "confident": 0.306, "low": 0.073, "veryLow": 0.255, "span": [ 1, 821 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P21802-F1" }, "experimentalCount": 65, "experimentalLatest": [ "9W2L", "9W19", "9VLM", "10OO", "10OQ", "10OU", "9U7E", "9U7S" ], "evidenceCount": 4 } ], "biomarkers": [ { "id": "BM-MSI-C", "name": "MSI-H / dMMR (colorectal)", "kind": "Selection biomarker (study-defined genomic state)", "assay": "Study-specific MMR / MSI assessment; see the linked source", "program": "colorectal", "def": "Mismatch-repair deficiency or high microsatellite instability as defined by each colorectal study. No single assay threshold is imposed across the studies.", "selects": [ "PDCD1" ], "units": [ "U-NICHE2", "U-DOSTrectal", "U-KN177" ], "caveat": "This genomic state is not a drug target. Findings in selected dMMR/MSI-H cohorts do not establish efficacy in all colorectal cancers or prove cure." }, { "id": "BM-HER2-G", "name": "HER2 status (gastric)", "kind": "Target and selection biomarker", "assay": "IHC with reflex ISH/FISH", "program": "gastric", "def": "Positive = IHC 3+ or IHC 2+ with ISH amplification, scored with gastric-specific criteria (Hofmann 2008; CAP/ASCP/ASCO 2017).", "selects": [ "ERBB2" ], "units": [ "U-Hofmann08", "U-GEAHER2", "U-ToGA", "U-DG04" ], "caveat": "Scoring differs from breast; heterogeneity is higher and status can be lost after trastuzumab." }, { "id": "BM-HER2-B", "name": "HER2 status (breast)", "kind": "Target and selection biomarker", "assay": "IHC with reflex ISH", "program": "breast", "def": "Positive = IHC 3+ or ISH-amplified, per ASCO–CAP.", "selects": [ "ERBB2" ], "units": [ "U-ASCOCAP23" ], "caveat": "" }, { "id": "BM-HER2LOW-B", "name": "HER2-low / ultralow (breast)", "kind": "Selection biomarker", "assay": "IHC", "program": "breast", "def": "HER2-low = IHC 1+ or 2+/ISH−; ultralow = IHC 0 with faint membrane staining. Crosses HR+/HER2− and TNBC.", "selects": [ "ERBB2" ], "units": [ "U-DB04", "U-DB06", "U-ASCOCAP23" ], "caveat": "An expression level that selects an ADC, not a new subtype." }, { "id": "BM-HER2LOW-G", "name": "HER2-low (gastric)", "kind": "Exploratory biomarker", "assay": "IHC", "program": "gastric", "def": "IHC 2+/ISH− or IHC 1+ in the DESTINY-Gastric01 exploratory cohorts.", "selects": [ "ERBB2" ], "units": [ "U-DG01" ], "caveat": "Exploratory only: five and two partial responses." }, { "id": "BM-pERBB2", "name": "Plasma ERBB2 amplification", "kind": "Exploratory biomarker", "assay": "ctDNA", "program": "gastric", "def": "ERBB2 amplification detected in plasma.", "selects": [ "ERBB2" ], "units": [ "U-DG01" ], "caveat": "64% concordance with tissue HER2 positivity in DESTINY-Gastric01." }, { "id": "BM-HER2HET", "name": "HER2 heterogeneity (gastric)", "kind": "Exploratory biomarker", "assay": "ISH", "program": "gastric", "def": "Genetic heterogeneity of HER2 amplification within a tumour.", "selects": [], "units": [ "U-GASTHER3" ], "caveat": "2.9% at baseline, 21.9% at second biopsy in GASTHER3." }, { "id": "BM-COAMP", "name": "Co-alterations with ERBB2", "kind": "Hypothesis", "assay": "NGS / copy number", "program": "gxb", "def": "Amplification or mutation of RTK, RAS, PI3K or cell-cycle genes in ERBB2-amplified tumours.", "selects": [], "units": [ "U-Janjigian18", "U-A1" ], "caveat": "Associated with trastuzumab resistance in one esophagogastric cohort; descriptive frequencies only in A1." }, { "id": "BM-CLDN18", "name": "CLDN18.2 IHC", "kind": "Target and selection biomarker", "assay": "IHC", "program": "gastric", "def": "Membranous CLDN18 staining; thresholds differ by study.", "selects": [ "CLDN18.2" ], "units": [ "U-SPOTLIGHT", "U-GLOW", "U-CT041" ], "caveat": "≥75% moderate-to-strong (SPOTLIGHT) vs ≥2+ in ≥40% (CT041-ST-01)." }, { "id": "BM-PDL1-CPS", "name": "PD-L1 CPS (gastric)", "kind": "Selection biomarker", "assay": "IHC, combined positive score", "program": "gastric", "def": "Cut-offs ≥1 and ≥5 used in trials.", "selects": [ "PDCD1" ], "units": [ "U-CM649", "U-KN811", "U-KN062", "U-KN061", "U-NCI-PDQ" ], "caveat": "Selects PD-1 blockade; PD-L1 is not the drug target of pembrolizumab or nivolumab." }, { "id": "BM-PDL1-TAP", "name": "PD-L1 TAP score", "kind": "Selection biomarker", "assay": "IHC, tumour area positivity", "program": "gastric", "def": "Cut-off ≥5% in RATIONALE-305.", "selects": [ "PDCD1" ], "units": [ "U-RAT305" ], "caveat": "Not interchangeable with CPS without a concordance study." }, { "id": "BM-PDL1-B", "name": "PD-L1 (TNBC)", "kind": "Selection biomarker", "assay": "IHC", "program": "breast", "def": "PD-L1-positive population in IMpassion trials.", "selects": [ "CD274" ], "units": [ "U-IMP130", "U-IMP131" ], "caveat": "Same biomarker, conflicting outcomes." }, { "id": "BM-MSI", "name": "MSI-H / dMMR", "kind": "Selection biomarker (genomic state)", "assay": "IHC for MMR proteins or PCR for MSI", "program": "gastric", "def": "Mismatch-repair deficiency or high microsatellite instability.", "selects": [ "PDCD1" ], "units": [ "U-NCI-PDQ", "U-TCGASTAD" ], "caveat": "A genomic state, not a drug target." }, { "id": "BM-EBV", "name": "EBV-positive gastric", "kind": "Research classification", "assay": "EBER ISH / genomic", "program": "gastric", "def": "TCGA subtype with PIK3CA mutations and CD274/PDCD1LG2 amplification.", "selects": [], "units": [ "U-TCGASTAD" ], "caveat": "Not used to select therapy in the curated trials." }, { "id": "BM-ESR1", "name": "ESR1 mutation", "kind": "Selection biomarker", "assay": "Tissue NGS or ctDNA", "program": "breast", "def": "Ligand-binding-domain mutations (D538G, Y537S, E380Q…).", "selects": [ "ESR1" ], "units": [ "U-EMERALD", "U-PADA1", "U-SERENA6", "U-EMBER3", "U-VERITAC2", "U-A2" ], "caveat": "Mostly acquired under endocrine therapy (A2: 19.2% metastatic vs 2.6% primary, HR+/HER2−)." }, { "id": "BM-PI3K", "name": "PIK3CA / AKT1 / PTEN alterations", "kind": "Selection biomarker", "assay": "Tissue NGS or ctDNA", "program": "breast", "def": "PIK3CA mutation for PI3Kα inhibitors; AKT pathway alteration in CAPItello-291.", "selects": [ "PIK3CA", "AKT" ], "units": [ "U-SOLAR1", "U-INAVO120", "U-CAP291", "U-A2" ], "caveat": "PIK3CA frequency is similar in primary and metastatic samples (A2)." }, { "id": "BM-gBRCA", "name": "Germline BRCA1/2", "kind": "Selection biomarker", "assay": "Germline testing", "program": "breast", "def": "Pathogenic germline BRCA1 or BRCA2 variant.", "selects": [ "PARP1" ], "units": [ "U-OlympiA", "U-NCI-BREAST" ], "caveat": "" }, { "id": "BM-HR", "name": "ER / PR status", "kind": "Selection biomarker", "assay": "IHC", "program": "breast", "def": "Hormone-receptor positivity defines HR+ disease.", "selects": [ "ESR1", "CDK4/6" ], "units": [ "U-NCI-BREAST" ], "caveat": "" }, { "id": "BM-TROP2", "name": "TROP2 expression", "kind": "Target antigen, not a selection biomarker", "assay": "IHC", "program": "breast", "def": "Expression of the ADC target.", "selects": [], "units": [ "U-TROPiCS02" ], "caveat": "Benefit consistent across expression levels in TROPiCS-02." } ], "pathways": [ { "id": "PW-ERBB", "name": "HER2 signalling and bypass", "note": "HER2 heterodimers signal through PI3K–AKT and RAS–MAPK. Co-amplified receptors are a proposed bypass route.", "nodes": [ [ "ERBB2", "HER2", "target" ], [ "ERBB3", "HER3", "plain" ], [ "PIK3CA", "PI3Kα", "target" ], [ "AKT", "AKT", "target" ], [ "MAPK", "RAS–MAPK", "plain" ], [ "RTK", "EGFR · MET · FGFR2", "plain" ], [ "CCNE1", "CCNE1", "plain" ] ], "edges": [ [ "ERBB2", "ERBB3", "dimerises with", [ "U-HER2Pert" ] ], [ "ERBB3", "PIK3CA", "activates", [] ], [ "PIK3CA", "AKT", "activates", [] ], [ "ERBB2", "MAPK", "activates", [] ], [ "RTK", "MAPK", "bypass (hypothesis)", [ "U-Janjigian18", "U-A1" ] ], [ "CCNE1", "ERBB2", "co-amplified in 31% of ERBB2-amp gastric (A1)", [ "U-A1" ] ] ] }, { "id": "PW-PI3K", "name": "PI3K–AKT–mTOR", "note": "Three drug classes act at three points of one pathway.", "nodes": [ [ "PIK3CA", "PI3Kα", "target" ], [ "AKT", "AKT", "target" ], [ "MTOR", "mTOR", "plain" ] ], "edges": [ [ "PIK3CA", "AKT", "activates", [] ], [ "AKT", "MTOR", "activates", [] ] ], "drugs": [ [ "PIK3CA", "alpelisib · inavolisib · RLY-2608" ], [ "AKT", "capivasertib" ], [ "MTOR", "everolimus" ] ] }, { "id": "PW-ER", "name": "ER signalling and the cell cycle", "note": "Endocrine therapy and CDK4/6 inhibitors act on two linked steps; ESR1 mutations change the first.", "nodes": [ [ "E2", "Oestrogen", "plain" ], [ "ESR1", "ERα", "target" ], [ "CDK4/6", "CDK4/6", "target" ], [ "RB", "RB–E2F", "plain" ] ], "edges": [ [ "E2", "ESR1", "binds", [ "U-ERago" ] ], [ "ESR1", "CDK4/6", "drives cyclin D–CDK4/6", [] ], [ "CDK4/6", "RB", "phosphorylates", [] ] ], "drugs": [ [ "ESR1", "elacestrant · camizestrant · imlunestrant · vepdegestrant" ], [ "CDK4/6", "abemaciclib · palbociclib · ribociclib" ] ] }, { "id": "PW-IMMUNE", "name": "PD-1 / PD-L1 checkpoint", "note": "The drug target and the selection biomarker are different molecules for pembrolizumab and nivolumab.", "nodes": [ [ "CD274", "PD-L1", "target" ], [ "PDCD1", "PD-1", "target" ], [ "TCELL", "T-cell activity", "plain" ] ], "edges": [ [ "CD274", "PDCD1", "binds", [] ], [ "PDCD1", "TCELL", "inhibits", [] ] ], "drugs": [ [ "PDCD1", "pembrolizumab · nivolumab · tislelizumab" ], [ "CD274", "atezolizumab" ] ] }, { "id": "PW-VEGF", "name": "VEGF–VEGFR2 angiogenesis", "note": "Ramucirumab blocks the receptor.", "nodes": [ [ "VEGF", "VEGF-A", "plain" ], [ "KDR", "VEGFR2", "target" ], [ "ANGIO", "Angiogenesis", "plain" ] ], "edges": [ [ "VEGF", "KDR", "binds", [] ], [ "KDR", "ANGIO", "drives", [] ] ], "drugs": [ [ "KDR", "ramucirumab" ] ] }, { "id": "PW-DDR", "name": "DNA damage repair", "note": "PARP inhibition is selected by germline BRCA status.", "nodes": [ [ "PARP1", "PARP1/2", "target" ], [ "BRCA", "BRCA1/2", "plain" ], [ "HR", "Homologous recombination", "plain" ] ], "edges": [ [ "BRCA", "HR", "required for", [] ], [ "PARP1", "HR", "dependence when BRCA is lost", [ "U-OlympiA" ] ] ], "drugs": [ [ "PARP1", "olaparib · talazoparib" ] ] }, { "id": "PW-SURFACE", "name": "Surface antigens for delivery", "note": "Not a signalling pathway. Antibodies, ADCs and CAR T cells use these proteins as addresses.", "nodes": [ [ "ERBB2", "HER2", "target" ], [ "TACSTD2", "TROP2", "target" ], [ "CLDN18.2", "CLDN18.2", "target" ] ], "edges": [], "drugs": [ [ "ERBB2", "T-DXd · T-DM1 · zanidatamab" ], [ "TACSTD2", "sacituzumab govitecan · Dato-DXd" ], [ "CLDN18.2", "zolbetuximab · satri-cel" ] ] } ], "therapeutics": [ { "cls": "Anti-HER2 antibody", "agents": "trastuzumab · pertuzumab · margetuximab", "target": "ERBB2", "gastric": [ "NCI (trastuzumab)", "Phase 3 negative (pertuzumab, JACOB)" ], "breast": [ "NCI" ], "units": [ "U-ToGA", "U-JACOB", "U-CLEOPATRA" ] }, { "cls": "HER2 antibody–drug conjugate", "agents": "trastuzumab deruxtecan · trastuzumab emtansine", "target": "ERBB2", "gastric": [ "NCI (T-DXd)", "Phase 3 negative (T-DM1, GATSBY)" ], "breast": [ "NCI" ], "units": [ "U-DG04", "U-GATSBY", "U-DB03", "U-EMILIA" ] }, { "cls": "HER2 tyrosine kinase inhibitor", "agents": "lapatinib · neratinib · tucatinib", "target": "ERBB2", "gastric": [ "Phase 3 negative (lapatinib, LOGiC, TyTAN)" ], "breast": [ "NCI" ], "units": [ "U-LOGiC", "U-TyTAN", "U-HER2CLIMB" ] }, { "cls": "HER2 bispecific antibody", "agents": "zanidatamab", "target": "ERBB2", "gastric": [ "Phase 3 positive (HERIZON-GEA-01, 2026)", "Not in NCI PDQ page" ], "breast": [ "Not in library" ], "units": [ "U-HERIZON" ] }, { "cls": "Anti-CLDN18.2 antibody", "agents": "zolbetuximab", "target": "CLDN18.2", "gastric": [ "NCI" ], "breast": [ "Not in library" ], "units": [ "U-SPOTLIGHT", "U-GLOW" ] }, { "cls": "CLDN18.2 CAR T cells", "agents": "satri-cel", "target": "CLDN18.2", "gastric": [ "Randomised phase 2 positive", "Investigational" ], "breast": [ "Not in library" ], "units": [ "U-CT041" ] }, { "cls": "Anti-PD-1 antibody", "agents": "nivolumab · pembrolizumab · tislelizumab", "target": "PDCD1", "gastric": [ "NCI (nivolumab, pembrolizumab)", "Phase 3 positive (tislelizumab; not in NCI PDQ page)" ], "breast": [ "NCI (pembrolizumab, TNBC)" ], "units": [ "U-CM649", "U-KN859", "U-RAT305", "U-KN522" ] }, { "cls": "Anti-PD-L1 antibody", "agents": "atezolizumab", "target": "CD274", "gastric": [ "Not in library" ], "breast": [ "Conflicting phase 3 (IMpassion130/131)" ], "units": [ "U-IMP130", "U-IMP131" ] }, { "cls": "Anti-VEGFR2 antibody", "agents": "ramucirumab", "target": "KDR", "gastric": [ "NCI" ], "breast": [ "Not in library" ], "units": [ "U-RAINBOW", "U-REGARD", "U-RAINFALL" ] }, { "cls": "CDK4/6 inhibitor", "agents": "abemaciclib · palbociclib · ribociclib", "target": "CDK4/6", "gastric": [ "Not in library" ], "breast": [ "NCI", "Adjuvant split (monarchE/NATALEE vs PALLAS/PENELOPE-B)" ], "units": [ "U-monarchE", "U-NATALEE", "U-PALLAS", "U-PENELOPEB" ] }, { "cls": "PI3Kα inhibitor", "agents": "alpelisib · inavolisib", "target": "PIK3CA", "gastric": [ "Not in library" ], "breast": [ "NCI" ], "units": [ "U-SOLAR1", "U-INAVO120" ] }, { "cls": "Mutant-selective PI3Kα inhibitor", "agents": "RLY-2608", "target": "PIK3CA", "gastric": [ "Not in library" ], "breast": [ "Investigational (phase 1; phase 3 registered)" ], "units": [ "U-RLY2608" ] }, { "cls": "AKT inhibitor", "agents": "capivasertib", "target": "AKT", "gastric": [ "Not in library" ], "breast": [ "NCI" ], "units": [ "U-CAP291" ] }, { "cls": "mTOR inhibitor", "agents": "everolimus", "target": null, "gastric": [ "Not in library" ], "breast": [ "NCI" ], "units": [ "U-NCI-BREAST" ] }, { "cls": "Oral ER antagonist / degrader", "agents": "elacestrant · camizestrant · imlunestrant · vepdegestrant", "target": "ESR1", "gastric": [ "Not in library" ], "breast": [ "NCI (camizestrant on targeted-therapy page)", "Phase 3 (all four)" ], "units": [ "U-EMERALD", "U-SERENA6", "U-EMBER3", "U-VERITAC2" ] }, { "cls": "PARP inhibitor", "agents": "olaparib · talazoparib", "target": "PARP1", "gastric": [ "Not in library" ], "breast": [ "NCI" ], "units": [ "U-OlympiA" ] }, { "cls": "TROP2 antibody–drug conjugate", "agents": "sacituzumab govitecan · datopotamab deruxtecan", "target": "TACSTD2", "gastric": [ "Not in library" ], "breast": [ "NCI" ], "units": [ "U-ASCENT", "U-TROPiCS02", "U-TROPIONB01" ] } ], "datasets": [ { "id": "D-STAD", "name": "TCGA Stomach Adenocarcinoma (PanCancer Atlas)", "where": "cBioPortal study stad_tcga_pan_can_atlas_2018", "access": "Open (summary-level via cBioPortal); raw data controlled through GDC/dbGaP", "status": "Connected", "size": "440 samples; 438 with copy-number calls", "used": [ "A1" ], "questions": "Frequency and co-occurrence of alterations in primary gastric tumours.", "limits": "Treatment-naive primary resections; no response data." }, { "id": "D-BRCA", "name": "TCGA Breast Invasive Carcinoma (PanCancer Atlas)", "where": "cBioPortal study brca_tcga_pan_can_atlas_2018", "access": "Open (summary-level); raw controlled", "status": "Connected", "size": "1,084 samples; 1,070 with copy-number calls; 1,066 sequenced", "used": [ "A1", "A2" ], "questions": "Primary-tumour reference frequencies by PAM50 subtype.", "limits": "Primary tumours; subtype from PAM50 in the study data." }, { "id": "D-MSK18", "name": "Breast Cancer (MSK, Cancer Cell 2018)", "where": "cBioPortal study breast_msk_2018 (Razavi et al.)", "access": "Open (summary-level)", "status": "Connected", "size": "1,918 samples: 918 primary, 1,000 metastasis", "used": [ "A2", "A5" ], "questions": "Alterations in treated, metastatic HR+ disease.", "limits": "Single institution; cross-sectional; sequencing panel." }, { "id": "D-METABRIC", "name": "METABRIC", "where": "cBioPortal study brca_metabric; frozen brca_metabric_2012 subset", "access": "Open processed data via cBioPortal; ODbL attribution and shared/adapted database conditions apply", "status": "Connected", "size": "1,980 primary-tumour samples in the frozen original cohort", "used": [ "CV-A1", "CV-A3 (reused comparator)" ], "questions": "Descriptive primary-tumour co-amplification comparison; survival and treatment benefit not evaluated.", "limits": "Original 2012 subset only, with complete calls for six prespecified genes. Affymetrix SNP6/DNAcopy calls are not interchangeable with gastric assay thresholds. CV-A3 reuses the CV-A1 comparator and adds no new METABRIC patients. Global donor deduplication across anonymous studies is unproven. Processed-data access does not grant raw-source access; no new biological validation is implied." }, { "id": "D-CPTAC", "name": "CPTAC breast proteogenomics", "where": "PDC / cBioPortal", "access": "Open (to confirm)", "status": "Planned", "size": "", "used": [], "questions": "Protein-level HER2 and pathway activity.", "limits": "" }, { "id": "D-GENIE", "name": "AACR Project GENIE", "where": "Synapse", "access": "Registration and data-use terms", "status": "Not Connected", "size": "", "used": [], "questions": "Independent replication of A2 in a multi-institution cohort.", "limits": "Project access approval and verified data acquisition are not documented in this library. The account and current terms-of-access requirements must be met, or shown to have been met, before a pinned release is connected." }, { "id": "D-DEPMAP", "name": "DepMap / CCLE", "where": "depmap.org", "access": "Pinned 24Q4 Public v1: CC BY 4.0 verified; only Model.csv received", "status": "Planned", "size": "1 of 5 required files received and checksum verified", "used": [], "questions": "Cell-line dependency on ERBB2, PIK3CA, ESR1 by lineage.", "limits": "Required matrices and profile mappings are still missing; A4 has not been run. Cell-model results are not patient treatment outcomes." }, { "id": "D-THCA", "name": "TCGA Thyroid Carcinoma (PanCancer Atlas) with GDC clinical table", "where": "cBioPortal study thca_tcga_pan_can_atlas_2018; open GDC clinical biotab for TCGA-THCA", "access": "Open", "status": "Connected", "size": "507 patients in the clinical table; 490 sequenced samples", "used": [ "A6" ], "questions": "Tumour alterations by recorded thyroid history in papillary thyroid cancer.", "limits": "Thyroid history is a site-reported field, not uniform pathology review; surgical cases only." }, { "id": "D-CRCMSK", "name": "Metastatic Colorectal Cancer (MSK, Cancer Cell 2018)", "where": "cBioPortal study crc_msk_2017 (Yaeger et al.)", "access": "Open (summary-level)", "status": "Connected", "size": "1,134 samples from 1,099 patients: 601 primary, 533 metastasis", "used": [ "A7" ], "questions": "Co-occurrence of ERBB2 amplification with RAS and BRAF status in metastatic colorectal cancer.", "limits": "Single institution; targeted panel; discrete copy-number calls, not the HER2-positive definition used in trials." }, { "id": "D-CRCMSK26", "name": "Colorectal Adenocarcinoma (MSK, 2026)", "where": "cBioPortal study crc_msk_2026 (portal API; not in DataHub)", "access": "Open (summary-level)", "status": "Connected", "size": "7,237 samples from 6,789 patients; 6,513 patients with a determined MSI label analysed", "used": [ "A8" ], "questions": "BRAF V600E frequency by MSI status.", "limits": "Single institution; targeted panels; MSI from MSIsensor sample labels; many patients also appear in earlier MSK studies in this library." }, { "id": "D-CRCDFCI16", "name": "Colorectal Adenocarcinoma (DFCI, Cell Reports 2016)", "where": "cBioPortal study coadread_dfci_2016 (Giannakis et al.)", "access": "Open (summary-level)", "status": "Connected", "size": "619 patients; 529 with an MSI label analysed", "used": [ "A8" ], "questions": "BRAF V600E frequency by MSI status.", "limits": "Patients from two United States prospective cohort studies; whole-exome sequencing; MSI as labelled in the study." }, { "id": "D-CRCGNE12", "name": "Colorectal Adenocarcinoma (Genentech, Nature 2012)", "where": "cBioPortal study coadread_genentech (Seshagiri et al.)", "access": "Open (summary-level)", "status": "Connected", "size": "74 patients; 72 sequenced and analysed", "used": [ "A8" ], "questions": "BRAF V600E frequency by MSI status.", "limits": "Small series; whole-exome sequencing; MSI as labelled in the study." }, { "id": "D-MSK50K", "name": "MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)", "where": "cBioPortal study msk_impact_50k_2026 (Bandlamudi et al.; portal API)", "access": "Open; CC BY-NC-ND 4.0 (only aggregate results are published)", "status": "Connected", "size": "54,331 samples; 867 thyroid cancer samples, 722 patients analysed for A9", "used": [ "A9" ], "questions": "BRAF V600E by thyroid cancer histology.", "limits": "Single institution; targeted panels; histology as recorded in the portal; tertiary-referral case mix; licence forbids redistribution of derivatives, so only aggregates are shown." }, { "id": "D-GDC", "name": "NCI Genomic Data Commons", "where": "portal.gdc.cancer.gov", "access": "Open and controlled tiers", "status": "Planned", "size": "", "used": [], "questions": "Harmonised raw data for re-analysis.", "limits": "Controlled data require dbGaP approval." }, { "id": "D-AFDB", "name": "AlphaFold Protein Structure Database", "where": "alphafold.ebi.ac.uk (API /api/prediction)", "access": "Open; licence stated on the site, not re-verified in this draft", "status": "Connected", "size": "14 entries saved (13 canonical + CLDN18 isoform A2)", "used": [ "Structure Lab" ], "questions": "Predicted models and confidence for target proteins.", "limits": "Predictions, not experimental structures; single static state." }, { "id": "D-PDB", "name": "RCSB Protein Data Bank", "where": "data.rcsb.org, search.rcsb.org", "access": "Open", "status": "Connected", "size": "20 entries saved; counts for 13 proteins", "used": [ "Structure Lab" ], "questions": "Experimental structures and complexes.", "limits": "" }, { "id": "D-UNIPROT", "name": "UniProt", "where": "rest.uniprot.org", "access": "Open", "status": "Connected", "size": "13 entries", "used": [ "A3", "Structure Lab" ], "questions": "Sequences, isoforms, topology.", "limits": "" }, { "id": "D-CTGOV", "name": "ClinicalTrials.gov", "where": "API v2", "access": "Open", "status": "Connected", "size": "53 trial records; benchmark counts", "used": [ "Clinical Trial Radar", "Benchmark" ], "questions": "Trial status, design, sponsors, results posting.", "limits": "Trials registered only in jRCT, ChiCTR, CRIS or EU CTR are missed." }, { "id": "D-PUBMED", "name": "PubMed", "where": "NCBI E-utilities", "access": "Open", "status": "Connected", "size": "83 papers; benchmark counts", "used": [ "Literature Observatory", "Benchmark" ], "questions": "Bibliographic records and abstracts.", "limits": "Affiliation search relies on string matching." }, { "id": "D-MSKEGC", "name": "MSK esophagogastric cohort (Janjigian 2018)", "where": "cBioPortal (study id to confirm)", "access": "Open (summary-level, to confirm)", "status": "Planned", "size": "", "used": [], "questions": "Replication of A1 with treatment data.", "limits": "" } ], "analyses": [ { "id": "A1", "unit": "U-A1", "title": "ERBB2 amplification and co-amplification, TCGA gastric vs breast", "run": "node scripts/run-analyses.mjs", "output": "data/analyses/A1-erbb2-amplification.json", "data": [ "D-STAD", "D-BRCA" ], "date": "2026-09-28", "kind": "Descriptive count", "status": "Executed", "result": { "id": "A1", "title": "ERBB2 amplification and co-amplification in TCGA gastric (STAD) and breast (BRCA) tumours", "retrieved": "2026-09-28", "method": "cBioPortal public API; GISTIC 2.0 discrete calls, value 2 = high-level amplification; denominator = samples with CNA data", "results": [ { "study": "stad_tcga_pan_can_atlas_2018", "sampleList": "stad_tcga_pan_can_atlas_2018_cna", "profile": "stad_tcga_pan_can_atlas_2018_gistic", "samples": 438, "erbb2Amplified": 58, "genes": { "ERBB2": { "amplified": 58, "pct": 13.2 }, "GRB7": { "amplified": 58, "pct": 13.2, "withERBB2": 58, "pctOfERBB2amp": 100 }, "CDK12": { "amplified": 39, "pct": 8.9, "withERBB2": 39, "pctOfERBB2amp": 67.2 }, "EGFR": { "amplified": 23, "pct": 5.3, "withERBB2": 4, "pctOfERBB2amp": 6.9 }, "MET": { "amplified": 12, "pct": 2.7, "withERBB2": 3, "pctOfERBB2amp": 5.2 }, "FGFR2": { "amplified": 19, "pct": 4.3, "withERBB2": 4, "pctOfERBB2amp": 6.9 }, "KRAS": { "amplified": 35, "pct": 8, "withERBB2": 2, "pctOfERBB2amp": 3.4 }, "CCNE1": { "amplified": 49, "pct": 11.2, "withERBB2": 18, "pctOfERBB2amp": 31 } }, "erbb2WithAnyOf": { "genes": [ "EGFR", "MET", "FGFR2", "KRAS", "CCNE1" ], "n": 27, "pct": 46.6 } }, { "study": "brca_tcga_pan_can_atlas_2018", "sampleList": "brca_tcga_pan_can_atlas_2018_cna", "profile": "brca_tcga_pan_can_atlas_2018_gistic", "samples": 1070, "erbb2Amplified": 123, "genes": { "ERBB2": { "amplified": 123, "pct": 11.5 }, "GRB7": { "amplified": 122, "pct": 11.4, "withERBB2": 122, "pctOfERBB2amp": 99.2 }, "CDK12": { "amplified": 111, "pct": 10.4, "withERBB2": 109, "pctOfERBB2amp": 88.6 }, "EGFR": { "amplified": 17, "pct": 1.6, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "MET": { "amplified": 4, "pct": 0.4, "withERBB2": 0, "pctOfERBB2amp": 0 }, "FGFR2": { "amplified": 16, "pct": 1.5, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "KRAS": { "amplified": 15, "pct": 1.4, "withERBB2": 2, "pctOfERBB2amp": 1.6 }, "CCNE1": { "amplified": 33, "pct": 3.1, "withERBB2": 4, "pctOfERBB2amp": 3.3 } }, "erbb2WithAnyOf": { "genes": [ "EGFR", "MET", "FGFR2", "KRAS", "CCNE1" ], "n": 9, "pct": 7.3 } } ] } }, { "id": "A2", "unit": "U-A2", "title": "ESR1 and PIK3CA mutations, primary vs metastatic breast samples", "run": "node scripts/run-analyses.mjs", "output": "data/analyses/A2-esr1-pik3ca-primary-vs-metastatic.json", "data": [ "D-MSK18", "D-BRCA" ], "date": "2026-09-28", "kind": "Descriptive count", "status": "Executed", "result": { "id": "A2", "title": "ESR1 and PIK3CA mutations in primary and metastatic breast tumour samples (MSK-IMPACT, Razavi et al. 2018) with TCGA luminal primaries as reference", "retrieved": "2026-09-28", "method": "cBioPortal public API; non-synonymous mutations; one count per sample; groups by SAMPLE_TYPE, HR_STATUS and OVERALL_HER2_STATUS as recorded in the study", "msk": { "study": "breast_msk_2018", "sampleList": "breast_msk_2018_sequenced", "groups": { "Primary": { "all": { "ESR1": { "mutated": 21, "samples": 918, "pct": 2.3 }, "PIK3CA": { "mutated": 362, "samples": 918, "pct": 39.4 } }, "hrPosHer2Neg": { "ESR1": { "mutated": 19, "samples": 733, "pct": 2.6 }, "PIK3CA": { "mutated": 320, "samples": 733, "pct": 43.7 }, "ESR1top": [ "Y537S 4", "D538G 3", "E380Q 2", "G521Rfs*18 1", "S432L 1", "L466Q 1" ] } }, "Metastasis": { "all": { "ESR1": { "mutated": 143, "samples": 1000, "pct": 14.3 }, "PIK3CA": { "mutated": 363, "samples": 1000, "pct": 36.3 } }, "hrPosHer2Neg": { "ESR1": { "mutated": 121, "samples": 629, "pct": 19.2 }, "PIK3CA": { "mutated": 259, "samples": 629, "pct": 41.2 }, "ESR1top": [ "D538G 51", "Y537S 26", "E380Q 12", "Y537C 10", "Y537N 9", "L536H 4" ] } } } }, "tcga": { "study": "brca_tcga_pan_can_atlas_2018", "sampleList": "brca_tcga_pan_can_atlas_2018_sequenced", "all": { "ESR1": { "mutated": 9, "samples": 1066, "pct": 0.8 }, "PIK3CA": { "mutated": 347, "samples": 1066, "pct": 32.6 } }, "luminal": { "ESR1": { "mutated": 8, "samples": 696, "pct": 1.1 }, "PIK3CA": { "mutated": 296, "samples": 696, "pct": 42.5 } } } } }, { "id": "A3", "unit": "U-A3", "title": "CLDN18 isoform A1 vs A2 sequence comparison", "run": "node scripts/run-analyses.mjs", "output": "data/analyses/A3-cldn18-isoforms.json", "data": [ "D-UNIPROT" ], "date": "2026-09-28", "kind": "Sequence comparison", "status": "Executed", "result": { "id": "A3", "title": "CLDN18 isoform A1 (canonical) vs isoform A2 (CLDN18.2) sequence comparison", "retrieved": "2026-09-28", "method": "UniProt REST FASTA for both isoform accessions, position-by-position comparison; topology and alternative-sequence annotation read from the P56856 entry. The topology is annotated for the canonical isoform; whether it holds for A2 is not shown here.", "lengths": { "P56856-1": 261, "P56856-2": 261 }, "differingPositions": 21, "span": { "first": 2, "last": 69 }, "identicalFrom": 70, "differences": [ { "pos": 2, "a1": "S", "a2": "A" }, { "pos": 3, "a1": "T", "a2": "V" }, { "pos": 5, "a1": "T", "a2": "A" }, { "pos": 8, "a1": "V", "a2": "G" }, { "pos": 9, "a1": "V", "a2": "L" }, { "pos": 10, "a1": "A", "a2": "G" }, { "pos": 12, "a1": "L", "a2": "V" }, { "pos": 13, "a1": "L", "a2": "V" }, { "pos": 15, "a1": "I", "a2": "L" }, { "pos": 16, "a1": "L", "a2": "I" }, { "pos": 18, "a1": "L", "a2": "I" }, { "pos": 21, "a1": "C", "a2": "I" }, { "pos": 26, "a1": "G", "a2": "C" }, { "pos": 29, "a1": "M", "a2": "Q" }, { "pos": 37, "a1": "D", "a2": "N" }, { "pos": 42, "a1": "S", "a2": "A" }, { "pos": 45, "a1": "Q", "a2": "N" }, { "pos": 47, "a1": "E", "a2": "Q" }, { "pos": 56, "a1": "Q", "a2": "E" }, { "pos": 65, "a1": "P", "a2": "G" }, { "pos": 69, "a1": "I", "a2": "L" } ], "topology": [ { "type": "Topological domain", "start": 1, "end": 6, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 7, "end": 27, "description": "Helical" }, { "type": "Topological domain", "start": 28, "end": 80, "description": "Extracellular" }, { "type": "Transmembrane", "start": 81, "end": 101, "description": "Helical" }, { "type": "Topological domain", "start": 102, "end": 122, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 123, "end": 143, "description": "Helical" }, { "type": "Topological domain", "start": 144, "end": 174, "description": "Extracellular" }, { "type": "Transmembrane", "start": 175, "end": 195, "description": "Helical" }, { "type": "Topological domain", "start": 196, "end": 261, "description": "Cytoplasmic" } ], "alternativeSequence": [ { "start": 1, "end": 69, "description": "in isoform A2" } ], "regionsTouched": [ "Topological domain 1-6 (Cytoplasmic)", "Transmembrane 7-27 (Helical)", "Topological domain 28-80 (Extracellular)" ] } }, { "id": "A5", "unit": "U-A5", "title": "Paired ESR1 detection in primary and metastatic breast specimens", "run": "python3 scripts/run-paired-mutation.py --plan docs/A5-PLAN-2026-09-30.json --inputs data/analyses/inputs/A5/outcomes/manifest-decoder-v2.json --output-dir /tmp/iatheon-a5-replay", "output": "data/analyses/A5/stats-result.json", "data": [ "D-MSK18" ], "date": "2026-09-30", "kind": "Paired observational comparison", "status": "Executed", "by": "Codex (GPT-6)", "added": "2026-09-30", "result": { "id": "A5", "analysisType": "paired-esr1-discordance-v1", "status": "completed", "retrieved": "2026-09-30", "title": "Paired ESR1 detection in primary and metastatic breast specimens", "method": "One metadata-selected primary/metastatic pair per patient; non-synonymous ESR1 detection; exact two-sided McNemar test, exact discordant-direction interval and descriptive marginal Wilson intervals.", "executedAtUtc": "2026-09-30T00:36:32.980543+00:00", "studyId": "breast_msk_2018", "sourceCollectionId": "MSK-BREAST-2018", "paired": { "pairs": 42, "cells": { "neither": 35, "primaryOnly": 0, "metastasisOnly": 6, "both": 1 }, "discordantPairs": 6, "metastasisDirectionShare": 1, "directionExact95CI": [ 0.5407418735600996, 1 ], "mcnemarExactP": 0.03125, "primary": { "events": 1, "patients": 42, "proportion": 0.023809523809523808, "wilson95CI": [ 0.004215404134432506, 0.12321201573766649 ] }, "metastasis": { "events": 7, "patients": 42, "proportion": 0.16666666666666666, "wilson95CI": [ 0.08315916646398072, 0.3060400274464885 ] }, "pairedRiskDifference": 0.14285714285714285 }, "conclusion": "supported", "secondary": { "hrPositiveHer2NegativeBoth": { "pairs": 25, "cells": { "neither": 19, "primaryOnly": 0, "metastasisOnly": 5, "both": 1 }, "primaryEvents": 1, "metastasisEvents": 6, "pairedRiskDifference": 0.2, "inference": "descriptive_only" } }, "selectionSummary": { "clinicalSamples": 1918, "sequencedSamples": 1918, "esr1ProfiledSamples": 1918, "unprofiledOrUncoveredSequencedSamples": 0, "eligibleTissueSamplesExcludedForUnknownTime": 0, "selectedPairs": 42, "selectedSamples": 84, "chronology": { "metastasisLater": 38, "sameTime": 3, "metastasisEarlier": 1 } }, "limits": [ "Within-patient tissue detection discordance is not evidence of mutation acquisition or loss.", "Metastatic specimen collection is not necessarily later; ties and reverse ordering are retained and reported.", "No qualifying reported mutation is non-detection after assay-targeting checks, not proven base-level biological absence.", "Panel, coverage, specimen quality, treatment history and ascertainment may differ; no causal therapy or predictive validation claim.", "Only patients with both selected specimen types enter this retrospective comparison; no power threshold or general-population representativeness is assumed.", "The paired risk difference is a descriptive point estimate; no unpaired confidence interval is attached.", "This reuses the MSK source collection and is not an independent patient-cohort evaluation or new experiment.", "The missing-Entrez annotation decoder was amended after input retrieval under a preserved original scientific plan; implementation timing and outcome exposure are documented in the linked amendment." ], "planRef": { "path": "docs/A5-PLAN-2026-09-30.json", "sha256": "de5666490db73a7933944e46b2595552201e8fa1dbb7c30fcd3987d2023f1073" }, "inputsRef": { "path": "data/analyses/inputs/A5/outcomes/manifest-decoder-v2.json", "sha256": "7113391422e21203cdd5fbe70e18ff4d1c7f2b4c3aa8123b89cc7a1823bc246b" }, "implementation": { "path": "scripts/run-paired-mutation.py", "sha256": "d0ea6c02e8c7df930e82d2432c50eaed502ba45071bfb08e214dd2a3891b99f6" }, "software": { "python": "3.12.14", "packages": { "numpy": "2.2.6", "scipy": "1.15.3", "statsmodels": "0.14.4" } }, "implementationAmendment": { "path": "data/analyses/inputs/A5/code-history/implementation-amendment.json", "sha256": "435bd788121280eed0da93488a563fc56cebac03dcaaa35c6ec97d67ec200aff" } } }, { "id": "A6", "unit": "U-A6", "title": "BRAF V600E frequency by recorded lymphocytic thyroiditis in TCGA papillary thyroid cancer", "run": "python3 scripts/run-thyroiditis-braf.py --plan docs/A6-PLAN-2026-10-06.json --inputs data/analyses/inputs/A6/outcomes/manifest.json --output /tmp/iatheon-a6-replay.json", "output": "data/analyses/A6/stats-result.json", "data": [ "D-THCA" ], "date": "2026-10-06", "kind": "Two-group observational comparison", "status": "Executed", "by": "Claude", "added": "2026-10-06", "result": { "id": "A6", "analysisType": "thyroiditis-braf-association-v1", "status": "completed", "retrieved": "2026-10-06", "title": "BRAF V600E frequency by recorded lymphocytic thyroiditis in TCGA papillary thyroid cancer", "method": "Patients with a recorded thyroid-disorder history and a sequenced primary tumour; exposure is recorded lymphocytic thyroiditis; outcome is BRAF p.V600E in the primary tumour; two-sided Fisher exact test, Newcombe-Wilson interval for the difference and Wilson marginal intervals.", "executedAtUtc": "2026-10-06T11:10:16.792961+00:00", "studyId": "thca_tcga_pan_can_atlas_2018", "sourceCollectionId": "TCGA-THCA", "groups": [ { "role": "thyroiditis", "patients": 75, "brafV600E": 40, "proportion": 0.5333333333333333, "wilson95CI": [ 0.42157537389084965, 0.6418430366102965 ] }, { "role": "no_thyroiditis", "patients": 359, "brafV600E": 212, "proportion": 0.5905292479108635, "wilson95CI": [ 0.5389650707469896, 0.640176530687595 ] } ], "primary": { "endpoint": "BRAF_V600E_in_sequenced_primary_tumour", "contrast": "thyroiditis_minus_no_thyroiditis", "riskDifference": -0.05719591457753015, "newcombeWilson95CI": [ -0.17948530163078413, 0.06294242265019231 ], "twoSidedFisherExactP": 0.3705853295397361, "sampleOddsRatio": 0.7924528301886793, "contingencyTable": [ [ 40, 35 ], [ 212, 147 ] ], "tableRows": [ "thyroiditis", "no_thyroiditis" ], "tableColumns": [ "BRAF_V600E", "no_BRAF_V600E" ], "numberOfPrimaryTests": 1 }, "conclusion": "inconclusive", "selectionSummary": { "clinicalPatients": 507, "sequencedSamples": 490, "excludedPatients": { "unknownHistory": 58, "noSequencedPrimaryTumour": 15 }, "selectedThyroiditis": 75, "selectedNoThyroiditis": 359, "selectedPatients": 434, "selectionUsesOutcomes": false }, "limits": [ "Cross-sectional association among patients who already have papillary thyroid cancer; it says nothing about who develops cancer.", "Thyroiditis is a recorded history field from contributing sites, not a uniform pathology review; unrecorded thyroiditis is counted as absent.", "Patients with unavailable or unknown thyroid history are excluded, not imputed.", "One prespecified test; no adjustment for age, sex, histological variant or contributing site.", "The direction was expected from published pooled analyses; this is a prespecified retrospective reanalysis of public data, not a blinded prospective study.", "BRAF V600E status is a tumour feature, not a clinical outcome; no prognostic or treatment claim follows." ], "provenance": { "firstOutcomeRetrievalAtUtc": "2026-10-06T11:10:11.193230+00:00", "literatureKnownBeforeLock": true }, "planRef": { "path": "docs/A6-PLAN-2026-10-06.json", "sha256": "39d6e856fc07b993c615eee8f941e80281ccb27bcc00f561f9ba9b6a6c401342" }, "inputsRef": { "path": "data/analyses/inputs/A6/outcomes/manifest.json", "sha256": "138a5a16777547579f6ee1ab773473060b8d961555fa04d8e592b026fa2d8a94" }, "implementation": { "path": "scripts/run-thyroiditis-braf.py", "sha256": "1cf9a2ebde73fc3e0991f5f41eb1b510232d5a0dde4f889a46de97a052fc911d" }, "software": { "python": "3.13.5", "packages": { "numpy": "2.2.6", "scipy": "1.15.3", "statsmodels": "0.14.4" } } } }, { "id": "A7", "unit": "U-A7", "title": "ERBB2 amplification by RAS/BRAF status in MSK metastatic colorectal cancer", "run": "python3 scripts/run-erbb2-ras-braf.py --plan docs/A7-PLAN-2026-10-06.json --inputs data/analyses/inputs/A7/outcomes/manifest.json --output /tmp/iatheon-a7-replay.json", "output": "data/analyses/A7/stats-result.json", "data": [ "D-CRCMSK" ], "date": "2026-10-06", "kind": "Two-group observational comparison", "status": "Executed", "by": "Claude", "added": "2026-10-06", "result": { "id": "A7", "analysisType": "erbb2-amplification-by-ras-braf-v1", "status": "completed", "retrieved": "2026-10-06", "title": "ERBB2 amplification by RAS/BRAF status in MSK metastatic colorectal cancer", "method": "One sample per patient, primary tumour preferred; RAS/BRAF mutant means a KRAS or NRAS missense mutation at codon 12, 13, 59, 61, 117 or 146 or BRAF V600E; outcome is high-level ERBB2 amplification in the discrete copy-number profile; two-sided Fisher exact test, Newcombe-Wilson interval for the difference and Wilson marginal intervals.", "executedAtUtc": "2026-10-06T11:36:45.532406+00:00", "studyId": "crc_msk_2017", "sourceCollectionId": "MSK-CRC-2017", "groups": [ { "role": "wildtype", "patients": 514, "erbb2Amplified": 26, "proportion": 0.05058365758754864, "wilson95CI": [ 0.03475052036502392, 0.0730845281223348 ] }, { "role": "mutant", "patients": 585, "erbb2Amplified": 7, "proportion": 0.011965811965811967, "wilson95CI": [ 0.005808072697621002, 0.024491184519128344 ] } ], "primary": { "endpoint": "ERBB2_high_level_amplification", "contrast": "wildtype_minus_mutant", "riskDifference": 0.038617845621736674, "newcombeWilson95CI": [ 0.018429403584108585, 0.06194608875571976 ], "twoSidedFisherExactP": 0.0002563993262160211, "contingencyTable": [ [ 26, 488 ], [ 7, 578 ] ], "tableRows": [ "wildtype", "mutant" ], "tableColumns": [ "ERBB2_amplified", "not_amplified" ], "numberOfPrimaryTests": 1 }, "conclusion": "supported", "selectionSummary": { "clinicalSamples": 1134, "profiledSamples": 1134, "excludedSamples": { "notProfiledForMutationsAndCopyNumber": 0, "panelMissingRequiredGene": 0, "additionalSamplesOfSelectedPatients": 35 }, "selectedPatients": 1099, "selectionUsesOutcomes": false }, "limits": [ "Single-institution targeted-panel series of patients with metastatic colorectal cancer; not a population sample.", "Copy-number amplification is the discrete call in the public profile, not immunohistochemistry or in-situ hybridisation; it is not the HER2-positive definition used in trials.", "One prespecified test; no adjustment for tumour side, microsatellite status or prior treatment.", "The direction was expected from published reports; this is a prespecified retrospective reanalysis of public data, not a blinded prospective study.", "A molecular co-occurrence pattern is not a treatment effect; no response or survival claim follows.", "Patient identifiers of this institution also appear in other analysed studies; the same person could be counted in more than one study." ], "provenance": { "firstOutcomeRetrievalAtUtc": "2026-10-06T11:36:39.644404+00:00", "literatureKnownBeforeLock": true }, "planRef": { "path": "docs/A7-PLAN-2026-10-06.json", "sha256": "32d8e29493554f364b948cc7181130457f5ee419d03e8332590b3189f037320e" }, "inputsRef": { "path": "data/analyses/inputs/A7/outcomes/manifest.json", "sha256": "daa3e320e2de51015bec6434208c62fa5a8e5ab768a92a6a57e9f7b19d8c20c6" }, "implementation": { "path": "scripts/run-erbb2-ras-braf.py", "sha256": "bec3038cf1f1699174b6ca3c95804ccb1386fa585e9593dac61c51a6707ab3c1" }, "software": { "python": "3.13.5", "packages": { "numpy": "2.2.6", "scipy": "1.15.3", "statsmodels": "0.14.4" } } } }, { "id": "A8", "unit": "U-A8", "title": "BRAF V600E by MSI status in three colorectal cancer cohorts", "run": "python3 scripts/run-msi-braf.py --plan docs/A8-PLAN-2026-10-20.json --inputs data/analyses/inputs/A8/outcomes/manifest.json --output /tmp/iatheon-a8-replay.json", "output": "data/analyses/A8/result.json", "data": [ "D-CRCMSK26", "D-CRCDFCI16", "D-CRCGNE12" ], "date": "2026-10-20", "kind": "Two-group observational comparison in three cohorts", "status": "Executed", "by": "Claude", "added": "2026-10-20", "result": { "id": "A8", "analysisType": "braf-v600e-by-msi-status-v1", "status": "completed", "retrieved": "2026-10-20", "title": "BRAF V600E by MSI status in three colorectal cancer cohorts", "method": "One sample per patient with a determined MSI label, primary tumour preferred where sample type is recorded; BRAF V600E is a missense call with protein change V600E in the public mutation profile; MSI-high and microsatellite-stable groups compared with a two-sided Fisher exact test and a Newcombe-Wilson 95% interval for the difference, in each cohort separately. The MSK 2026 cohort is primary; DFCI 2016 and Genentech 2012 are prespecified replications, not pooled.", "executedAtUtc": "2026-10-20T01:57:03.681492+00:00", "primaryCohort": "MSK", "conclusion": "supported", "cohorts": [ { "cohortId": "MSK", "studyId": "crc_msk_2026", "label": "MSK colorectal cancer · 2026 portal study", "role": "primary", "groups": [ { "role": "msi_high", "patients": 749, "brafV600E": 259, "proportion": 0.34579439252336447, "wilson95CI": [ 0.3125969017084483, 0.38056558649742805 ] }, { "role": "mss", "patients": 5764, "brafV600E": 260, "proportion": 0.04510756419153366, "wilson95CI": [ 0.040045932539782454, 0.05077512462010001 ] } ], "primary": { "endpoint": "BRAF_V600E", "contrast": "msi_high_minus_mss", "riskDifference": 0.3006868283318308, "newcombeWilson95CI": [ 0.2670090220253343, 0.33582450106865225 ], "twoSidedFisherExactP": 1.9522946076958697e-118, "contingencyTable": [ [ 259, 490 ], [ 260, 5504 ] ], "tableRows": [ "msi_high", "mss" ], "tableColumns": [ "BRAF_V600E", "no_BRAF_V600E" ] }, "conclusion": "supported", "selectionSummary": { "portalSamples": 7237, "profiledSamples": 7237, "excludedSamples": { "notProfiledForMutations": 0, "msiNotDetermined": 353, "panelWithoutBraf": 0, "additionalSamplesOfSelectedPatients": 371 }, "selectedPatients": 6513, "selectionUsesOutcomes": false }, "brafMutationRecords": 774 }, { "cohortId": "DFCI", "studyId": "coadread_dfci_2016", "label": "DFCI colorectal cancer · Cell Reports 2016 (Nurses' Health Study and Health Professionals Follow-up Study)", "role": "replication", "groups": [ { "role": "msi_high", "patients": 91, "brafV600E": 53, "proportion": 0.5824175824175825, "wilson95CI": [ 0.47977166187867143, 0.6783870187923924 ] }, { "role": "mss", "patients": 438, "brafV600E": 37, "proportion": 0.08447488584474885, "wilson95CI": [ 0.061906423334929114, 0.11426866677195775 ] } ], "primary": { "endpoint": "BRAF_V600E", "contrast": "msi_high_minus_mss", "riskDifference": 0.49794269657283363, "newcombeWilson95CI": [ 0.39106026403493266, 0.5965300599525074 ], "twoSidedFisherExactP": 1.8992768696985286e-24, "contingencyTable": [ [ 53, 38 ], [ 37, 401 ] ], "tableRows": [ "msi_high", "mss" ], "tableColumns": [ "BRAF_V600E", "no_BRAF_V600E" ] }, "conclusion": "supported", "selectionSummary": { "portalSamples": 619, "profiledSamples": 619, "excludedSamples": { "notProfiledForMutations": 0, "msiNotDetermined": 90, "panelWithoutBraf": 0, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 529, "selectionUsesOutcomes": false }, "brafMutationRecords": 112 }, { "cohortId": "GNE", "studyId": "coadread_genentech", "label": "Genentech colorectal cancer · Nature 2012", "role": "replication", "groups": [ { "role": "msi_high", "patients": 15, "brafV600E": 2, "proportion": 0.13333333333333333, "wilson95CI": [ 0.03736125910306534, 0.3788198283232237 ] }, { "role": "mss", "patients": 57, "brafV600E": 2, "proportion": 0.03508771929824561, "wilson95CI": [ 0.009675664344932874, 0.11920781367625809 ] } ], "primary": { "endpoint": "BRAF_V600E", "contrast": "msi_high_minus_mss", "riskDifference": 0.09824561403508772, "newcombeWilson95CI": [ -0.029374248487271215, 0.3450438955513326 ], "twoSidedFisherExactP": 0.18942641355378642, "contingencyTable": [ [ 2, 13 ], [ 2, 55 ] ], "tableRows": [ "msi_high", "mss" ], "tableColumns": [ "BRAF_V600E", "no_BRAF_V600E" ] }, "conclusion": "inconclusive", "selectionSummary": { "portalSamples": 74, "profiledSamples": 72, "excludedSamples": { "notProfiledForMutations": 2, "msiNotDetermined": 0, "panelWithoutBraf": 0, "additionalSamplesOfSelectedPatients": 0 }, "selectedPatients": 72, "selectionUsesOutcomes": false }, "brafMutationRecords": 7 } ], "limits": [ "The association between BRAF V600E and MSI-high colorectal cancer is well established; agreement here confirms the handling of public data rather than adding new biology.", "MSI is the label each study provides (MSIsensor at MSK, study-specific calls in the other two); samples with indeterminate or missing labels were excluded, which may not be random.", "Only the BRAF V600E missense call is counted; other BRAF alterations are not.", "No adjustment for age, tumour side, stage or germline mismatch-repair status; sporadic and inherited MSI-high tumours are not separated, although they differ sharply in BRAF V600E frequency.", "The MSK 2026 cohort includes patients already counted in earlier MSK analyses of this library; the headline patient count removes them by hospital-wide identifier.", "The Genentech cohort is small; its inconclusive result reflects 15 MSI-high patients and does not contradict the other two cohorts.", "A molecular co-occurrence pattern is not a treatment effect." ], "provenance": { "firstOutcomeRetrievalAtUtc": "2026-10-20T01:56:57.181101+00:00", "literatureKnownBeforeLock": true }, "planRef": { "path": "docs/A8-PLAN-2026-10-20.json", "sha256": "7dd487b8fdb26a295594f443774c42a07d825a5f79d2e24c743c1af8ad8645b4", "lockedAtUtc": "2026-10-20T01:56:39.159113+00:00" }, "inputsRef": { "path": "data/analyses/inputs/A8/outcomes/manifest.json", "sha256": "58686454d7dbc7312fc14d02a527bbc868d8c1e53a10fca99dd18d0533f31422" }, "rawResult": { "path": "data/analyses/A8/stats-result.json", "sha256": "26eb9617ab6245bd1976bb6c8004ce07774664ff8b9572705b9e3cb5095c6dc7" }, "implementation": { "path": "scripts/run-msi-braf.py", "sha256": "db37677bb26c556694e249c84d7dd568be666f7e50f5f302f715904174c6bb50" }, "software": { "python": "3.13.5", "packages": { "numpy": "2.2.6", "scipy": "1.15.3", "statsmodels": "0.14.4" }, "runnerSha256": "db37677bb26c556694e249c84d7dd568be666f7e50f5f302f715904174c6bb50" } } }, { "id": "A9", "unit": "U-A9", "title": "BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer, MSK-IMPACT 50K", "run": "python3 scripts/run-thyroid-histology-braf.py --plan docs/A9-PLAN-2026-10-21.json --inputs data/analyses/inputs/A9/outcomes/manifest.json --output /tmp/iatheon-a9-replay.json", "output": "data/analyses/A9/result.json", "data": [ "D-MSK50K" ], "date": "2026-10-21", "kind": "Two-group observational comparison", "status": "Executed", "by": "Claude", "added": "2026-10-21", "result": { "id": "A9", "analysisType": "braf-v600e-papillary-vs-other-follicular-thyroid-v1", "status": "completed", "retrieved": "2026-10-21", "title": "BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer, MSK-IMPACT 50K", "method": "Thyroid cancer samples of the MSK-IMPACT 50K portal study; one sample per patient, primary tumour preferred; papillary carcinoma compared with follicular, Hurthle cell, poorly differentiated and anaplastic carcinoma taken together (medullary carcinoma not compared); BRAF V600E is a missense call with protein change V600E in the public mutation profile; two-sided Fisher exact test and Newcombe-Wilson 95% interval for the difference. Only aggregate results are published (CC BY-NC-ND 4.0 source).", "executedAtUtc": "2026-10-21T09:45:46.828391+00:00", "primaryCohort": "MSK50K", "conclusion": "supported", "cohorts": [ { "cohortId": "MSK50K", "studyId": "msk_impact_50k_2026", "label": "MSK-IMPACT 50K · thyroid cancer", "role": "primary", "groups": [ { "role": "papillary", "patients": 374, "brafV600E": 254, "proportion": 0.679144385026738, "wilson95CI": [ 0.6302194539894735, 0.7244266465687771 ] }, { "role": "other_follicular", "patients": 348, "brafV600E": 74, "proportion": 0.21264367816091953, "wilson95CI": [ 0.17291116242515187, 0.25865099437591954 ] } ], "primary": { "endpoint": "BRAF_V600E", "contrast": "papillary_minus_other_follicular", "riskDifference": 0.46650070686581846, "newcombeWilson95CI": [ 0.39934177579698676, 0.526743183716083 ], "twoSidedFisherExactP": 1.424764836414661e-37, "contingencyTable": [ [ 254, 120 ], [ 74, 274 ] ], "tableRows": [ "papillary", "other_follicular" ], "tableColumns": [ "BRAF_V600E", "no_BRAF_V600E" ] }, "conclusion": "supported", "selectionSummary": { "portalSamples": 54331, "profiledSamples": 54331, "excludedSamples": { "otherCancerType": 53464, "notProfiledForMutations": 0, "histologyNotCompared": 95, "panelWithoutBraf": 0, "additionalSamplesOfSelectedPatients": 50 }, "selectedPatients": 722, "selectionUsesOutcomes": false }, "brafMutationRecords": 345 } ], "limits": [ "The association between BRAF V600E and papillary thyroid carcinoma is well established; agreement here confirms the handling of public data rather than adding new biology.", "Histology is the detailed cancer type recorded in the portal, not central pathology review.", "The comparison group mixes four types with very different BRAF frequencies (rare in follicular and Hurthle cell carcinoma, more common in poorly differentiated and anaplastic carcinoma); the pooled proportion depends on that mix.", "Only the BRAF V600E missense call is counted; BRAF fusions and other alterations are not.", "A tertiary-referral series enriched for advanced and aggressive disease, with many metastatic samples; the frequencies are not population estimates.", "The source study is distributed under CC BY-NC-ND 4.0; only aggregate results are published and the source is attributed.", "A molecular co-occurrence pattern is not a treatment effect." ], "provenance": { "firstOutcomeRetrievalAtUtc": "2026-10-21T09:44:03.070036+00:00", "literatureKnownBeforeLock": true }, "planRef": { "path": "docs/A9-PLAN-2026-10-21.json", "sha256": "093d4ff408a2c7df21a614905c9c96cfb6543b470913a1847779f7e5dde7de29", "lockedAtUtc": "2026-10-21T09:42:33.729621+00:00" }, "inputsRef": { "path": "data/analyses/inputs/A9/outcomes/manifest.json", "sha256": "1c32cde5eddd214ee0c61138aeaec41c2bce3972d3bb6705bb75d594bb3ddd72" }, "rawResult": { "path": "data/analyses/A9/stats-result.json", "sha256": "64cfe9fd50fe9324a616aa3db36a91288da9781ac8edad76304d288d38533355" }, "implementation": { "path": "scripts/run-thyroid-histology-braf.py", "sha256": "ee8f70dfc6acdbae63bd4d595bfb32454fc32b874b872c58f668d0bb1b804d38" }, "software": { "python": "3.13.5", "packages": { "numpy": "2.2.6", "scipy": "1.15.3", "statsmodels": "0.14.4" }, "runnerSha256": "ee8f70dfc6acdbae63bd4d595bfb32454fc32b874b872c58f668d0bb1b804d38" } } } ], "evidence": [ { "id": "U-ToGA", "trial": "G-ToGA", "papers": [ { "key": "P-ToGA", "pmid": "20728210", "title": "Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.", "journal": "Lancet", "year": "2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20728210/", "doi": "10.1016/S0140-6736(10)61121-X", "errata": [ { "pmid": null, "title": "Lancet. 2010 Oct 16;376(9749):1302", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61919-8/fulltext", "reviewed": true, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "", "label": "ToGA", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, advanced", "population": "HER2-positive advanced gastric or GEJ cancer", "claim": "Trastuzumab plus chemotherapy improved median overall survival over chemotherapy alone: 13.8 vs 11.1 months (HR 0.74).", "trialRecord": { "key": "G-ToGA", "nct": "NCT01041404", "acronym": null, "title": "ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 584, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "Chugai Pharmaceutical" ], "hasResults": true, "start": "2005-09", "lastUpdate": "2014-11-05", "url": "https://clinicaltrials.gov/study/NCT01041404" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival in all randomised patients who received study medication at least once", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 594, "assessment": "not stated", "quote": "ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries … 594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290)." }, "effect": { "measure": "HR", "value": 0.74, "ci_low": 0.6, "ci_high": 0.91, "ci_level": "95%", "p": "0.0046", "endpoint": "Overall survival", "quote": "Median overall survival was 13.8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0.74; 95% CI 0.60-0.91; p=0.0046)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 68, "grade3plus_control_pct": 68, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not differ between groups." }, "takeaway_en": "In patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer, adding trastuzumab to first-line cisplatin plus capecitabine or fluorouracil improved median overall survival compared with chemotherapy alone (13.8 vs 11.1 months; hazard ratio 0.74). Rates of grade 3 or 4 adverse events were the same in both groups (68% vs 68%), as were rates of cardiac adverse events (6% vs 6%).", "takeaway_ko": "HER2 양성 진행성 위암 또는 위식도 접합부암 환자에서 1차 시스플라틴과 카페시타빈 또는 플루오로우라실 병용 항암화학요법에 트라스투주맙을 추가하자, 항암화학요법 단독보다 전체 생존기간 중앙값이 개선되었습니다(13.8개월 대 11.1개월; 위험비 0.74). 3~4등급 이상반응 발생률은 두 군에서 같았고(68% 대 68%), 심장 이상반응 발생률도 같았습니다(6% 대 6%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-Hofmann08", "trial": null, "papers": [ { "key": "P-Hofmann08", "pmid": "18422971", "title": "Assessment of a HER2 scoring system for gastric cancer: results from a validation study.", "journal": "Histopathology", "year": "2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18422971/", "doi": "10.1111/j.1365-2559.2008.03028.x", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "", "label": "Gastric HER2 scoring", "program": "gastric", "kind": "method", "level": "literature", "result": "descriptive", "population": "Gastric cancer specimens", "claim": "Validated a gastric-specific HER2 scoring system; the abstract notes that validated breast scoring systems did not exist for gastric cancer. The system was built to select patients for the trastuzumab trial.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-GEAHER2", "trial": null, "papers": [ { "key": "P-GEAHER2", "pmid": "28129524", "title": "HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology.", "journal": "J Clin Oncol", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28129524/", "doi": "10.1200/JCO.2016.69.4836", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HER2-G" ], "subtypes": [], "limits": "", "label": "CAP/ASCP/ASCO GEA HER2 guideline", "program": "gastric", "kind": "guideline", "level": "literature", "result": "descriptive", "population": "Gastroesophageal adenocarcinoma", "claim": "Joint guideline (2017) on HER2 testing and clinical decision making in gastroesophageal adenocarcinoma.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-DG01", "trial": "G-DG01", "papers": [ { "key": "P-DG01", "pmid": "32469182", "title": "Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.", "journal": "N Engl J Med", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32469182/", "doi": "10.1056/NEJMoa2004413", "errata": [] }, { "key": "P-DG01bio", "pmid": "38745009", "title": "Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.", "journal": "Nat Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38745009/", "doi": "10.1038/s41591-024-02992-x", "errata": [] }, { "key": "P-DG01low", "pmid": "36379002", "title": "Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36379002/", "doi": "10.1200/JCO.22.00575", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G", "BM-HER2LOW-G", "BM-pERBB2" ], "subtypes": [ "G-HER2" ], "limits": "Exploratory cohorts are small (five and two partial responses). The biomarker papers are the same trial and do not add independent evidence.", "label": "DESTINY-Gastric01", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Previously treated, advanced", "population": "HER2-positive advanced gastric cancer (primary cohort); HER2-low exploratory cohorts", "claim": "Trastuzumab deruxtecan vs physician's choice chemotherapy: objective response 51% vs 14%; overall survival 12.5 vs 8.4 months (HR 0.59). Exploratory analyses of the same trial: 64% concordance between tissue HER2 positivity and plasma ERBB2 amplification; in anti-HER2-naive HER2-low cohorts, confirmed response 26.3% (IHC 2+/ISH−) and 9.5% (IHC 1+).", "trialRecord": { "key": "G-DG01", "nct": "NCT03329690", "acronym": null, "title": "DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 233, "sponsor": "Daiichi Sankyo Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca" ], "hasResults": true, "start": "2017-11-02", "lastUpdate": "2022-03-18", "url": "https://clinicaltrials.gov/study/NCT03329690" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Objective response according to independent central review", "primary_endpoint_type": "ORR", "design": { "phase": "2", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "blinded independent central review", "quote": "In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. … were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. … Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel).", "quote_note": "P-DG01; the abstract says 'independent central review' without stating that it was blinded. It gives the 187 treated patients, not the number randomized." }, "effect": { "measure": "HR", "value": 0.59, "ci_low": 0.39, "ci_high": 0.88, "ci_level": "95%", "p": "0.01", "endpoint": "Overall survival (secondary end point; no effect measure reported for the primary end point, objective response)", "quote": "Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths])." }, "landmark": [ { "endpoint": "Objective response (independent central review)", "timepoint": "Primary analysis", "experimental_pct": 51, "control_pct": 14, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan 6.4 mg/kg every 3 weeks", "control_arm": "Physician's choice chemotherapy (irinotecan or paclitaxel)", "quote": "An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P<0.001).", "difference_pp": 37, "nnt": 3, "quote_note": "P-DG01, NEJM 2020; the only paper reporting both randomized arms" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "One drug-related death (pneumonia) in the trastuzumab deruxtecan group; none in the physician's choice group", "quote": "The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group.", "quote_note": "P-DG01; overall grade ≥3 rates and discontinuation rates not reported" }, "takeaway_en": "In patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma that progressed after at least two prior therapies including trastuzumab, trastuzumab deruxtecan produced an objective response in 51% versus 14% with physician's choice chemotherapy, with longer overall survival (median 12.5 vs 8.4 months; HR 0.59). The trade-off was more myelosuppression (grade ≥3 decreased neutrophil count 51% vs 24%, anemia 38% vs 23%) and 12 patients with drug-related interstitial lung disease or pneumonitis, plus one drug-related death in the trastuzumab deruxtecan group.", "takeaway_ko": "트라스투주맙을 포함한 2개 이상의 이전 치료 후 진행한 HER2 양성 진행성 위 또는 위식도접합부 선암 환자에서, 트라스투주맙 데룩스테칸의 객관적 반응률은 51%로 의사 선택 항암화학요법의 14%보다 높았고 전체생존도 더 길었습니다(중앙값 12.5개월 대 8.4개월, 위험비 0.59). 대신 골수억제가 더 많았고(3등급 이상 호중구 감소 51% 대 24%, 빈혈 38% 대 23%), 약물 관련 간질성 폐질환 또는 폐렴이 12명에서 발생했으며, 트라스투주맙 데룩스테칸군에서 약물 관련 사망이 1건 있었습니다.", "certainty": { "level": "moderate", "reasons": [ "surrogate primary endpoint (ORR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DG02", "trial": "G-DG02", "papers": [ { "key": "P-DG02", "pmid": "37329891", "title": "Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study.", "journal": "Lancet Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37329891/", "doi": "10.1016/S1470-2045(23)00215-2", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "No comparator arm.", "label": "DESTINY-Gastric02", "program": "gastric", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Second line after trastuzumab", "population": "HER2-positive gastric or GEJ cancer, USA and Europe", "claim": "Single-arm phase 2 (n=79). Eligibility required centrally confirmed HER2-positive disease on a post-progression biopsy. Confirmed objective response 38% (30/79).", "trialRecord": { "key": "G-DG02", "nct": "NCT04014075", "acronym": null, "title": "DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 79, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca" ], "hasResults": true, "start": "2019-11-26", "lastUpdate": "2025-04-03", "url": "https://clinicaltrials.gov/study/NCT04014075" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-DG04", "trial": "G-DG04", "papers": [ { "key": "P-DG04", "pmid": "40454632", "title": "Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454632/", "doi": "10.1056/NEJMoa2503119", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "Population limited to HER2-positive metastatic gastric/GEJ adenocarcinoma with positivity on biopsy after progression on trastuzumab-based therapy, treated second line; no inference to HER2-loss/low, other lines or settings. Safety among treated patients: drug-related grade ≥3 events 50.0% vs 54.1%; adjudicated drug-related ILD/pneumonitis 13.9% with T-DXd (33 grade 1/2, 1 grade 3) vs 1.3% with ramucirumab-paclitaxel (2 grade 3, 1 grade 5); overall safety not interpreted as comparable. Two CommentIn records are commentaries, not formal errata, and were not reviewed in full text here.", "label": "DESTINY-Gastric04", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Second line after trastuzumab", "population": "HER2-positive gastric cancer confirmed on a biopsy obtained after progression on first-line trastuzumab (ClinicalTrials.gov eligibility)", "claim": "In 494 randomized patients, trastuzumab deruxtecan improved median overall survival compared with ramucirumab plus paclitaxel (14.7 vs 11.4 months; HR 0.70; 95% CI 0.55-0.90; P=0.004), as well as progression-free survival (HR 0.74; 95% CI 0.59-0.92) and confirmed response lasting ≥4 weeks (44.3% vs 29.1%).", "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "trialRecord": { "key": "G-DG04", "nct": "NCT04704934", "acronym": null, "title": "Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 490, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca" ], "hasResults": false, "start": "2021-05-21", "lastUpdate": "2026-05-27", "url": "https://clinicaltrials.gov/study/NCT04704934" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 494, "assessment": "not stated", "quote": "We conducted an international, randomized, phase 3 trial comparing second-line trastuzumab deruxtecan at a dose of 6.4 mg per kilogram of body weight with ramucirumab plus paclitaxel in patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumor biopsy conducted after the patient had progression while receiving trastuzumab-based therapy. The primary end point was overall survival. … Among 494 patients who had undergone randomization" }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.55, "ci_high": 0.9, "ci_level": "95%", "p": "0.004", "endpoint": "Overall survival (hazard ratio for death)", "quote": "overall survival was significantly longer with trastuzumab deruxtecan than with ramucirumab plus paclitaxel (median, 14.7 vs. 11.4 months; hazard ratio for death, 0.70; 95% confidence interval, 0.55 to 0.90; P = 0.004)" }, "landmark": [ { "endpoint": "Confirmed objective response (complete or partial response lasting ≥4 weeks)", "timepoint": "Best confirmed response (no fixed time point)", "experimental_pct": 44.3, "control_pct": 29.1, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan 6.4 mg/kg", "control_arm": "Ramucirumab plus paclitaxel", "quote": "confirmed objective response (in 44.3% of the patients in the trastuzumab deruxtecan group vs. 29.1% of those in the ramucirumab-paclitaxel group)", "difference_pp": 15.2, "nnt": 7, "quote_note": "single paper, P-DG04, N Engl J Med 2025" } ], "harms": { "grade3plus_experimental_pct": 50, "grade3plus_control_pct": 54.1, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Not reported overall. One grade 5 adjudicated drug-related interstitial lung disease or pneumonitis event occurred in the ramucirumab plus paclitaxel group. No grade 5 ILD was reported with trastuzumab deruxtecan.", "quote": "the incidence of drug-related adverse events of grade 3 or higher was 50.0% and 54.1%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 13.9% of the patients who received trastuzumab deruxtecan (grade 1 or 2 in 33 patients and grade 3 in 1) and in 1.3% of those who received ramucirumab plus paclitaxel (grade 3 in 2 patients and grade 5 in 1)." }, "takeaway_en": "In patients with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma whose HER2 status was reconfirmed on biopsy after progression on trastuzumab-based therapy, second-line trastuzumab deruxtecan was compared with ramucirumab plus paclitaxel. Trastuzumab deruxtecan gave a confirmed response in 44.3% vs 29.1% of patients and longer median overall survival (14.7 vs 11.4 months; HR 0.70), with similar drug-related grade 3 or higher adverse events (50.0% vs 54.1%) but more drug-related interstitial lung disease or pneumonitis (13.9% vs 1.3%, mainly grade 1-2).", "takeaway_ko": "트라스투주맙 기반 치료 후 진행하여 재생검으로 HER2 양성이 재확인된 전이성 위암 또는 위식도접합부 선암 환자에서, 2차 치료로 트라스투주맙 데룩스테칸과 라무시루맙+파클리탁셀을 비교하였습니다. 트라스투주맙 데룩스테칸군은 확정 객관적 반응률이 44.3% 대 29.1%로 높았고 전체생존기간 중앙값도 14.7개월 대 11.4개월로 길었습니다(위험비 0.70). 약물 관련 3등급 이상 이상반응은 50.0% 대 54.1%로 비슷했으나, 약물 관련 간질성 폐질환/폐렴은 13.9% 대 1.3%로 더 많았으며 대부분 1-2등급이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-GATSBY", "trial": "G-GATSBY", "papers": [ { "key": "P-GATSBY", "pmid": "28343975", "title": "Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study.", "journal": "Lancet Oncol", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28343975/", "doi": "10.1016/S1470-2045(17)30111-0", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "", "label": "GATSBY", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Second line", "population": "Previously treated HER2-positive gastric or GEJ adenocarcinoma", "claim": "Trastuzumab emtansine 2.4 mg/kg weekly did not improve overall survival over taxane: 7.9 vs 8.6 months (HR 1.15, 95% CI 0.87–1.51).", "trialRecord": { "key": "G-GATSBY", "nct": "NCT01641939", "acronym": null, "title": "A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer", "status": "TERMINATED", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 415, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2012-09-03", "lastUpdate": "2017-05-12", "url": "https://clinicaltrials.gov/study/NCT01641939" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (intention-to-treat population)", "primary_endpoint_type": "OS", "design": { "phase": "2/3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide)." }, "effect": { "measure": "HR", "value": 1.15, "ci_low": 0.87, "ci_high": 1.51, "ci_level": "95%", "p": "one-sided p=0·86", "endpoint": "Overall survival, trastuzumab emtansine 2.4 mg/kg weekly vs taxane", "quote": "Median overall survival was 7·9 months (95% CI 6·7-9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1-11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87-1·51, one-sided p=0·86)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 60, "grade3plus_control_pct": 70, "discontinuation_experimental_pct": 14, "discontinuation_control_pct": 14, "treatment_related_deaths": "Treatment-related deaths not reported separately; adverse events leading to death: eight [4%] vs four [4%]", "quote": "The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment." }, "takeaway_en": "In patients with HER2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma that progressed after first-line therapy, trastuzumab emtansine 2.4 mg/kg weekly did not improve overall survival compared with a taxane: median 7.9 vs 8.6 months (hazard ratio 1.15, 95% CI 0.87–1.51). Grade 3 or higher adverse events were less frequent with trastuzumab emtansine (60% vs 70%), and discontinuation for adverse events was similar (14% vs 14%); the main grade 3 or higher toxicities were anaemia and thrombocytopenia with trastuzumab emtansine and neutropenia with taxane.", "takeaway_ko": "1차 치료 후 진행한 HER2 양성 진행성 위암 또는 위식도접합부 선암 환자에서 트라스투주맙 엠탄신(2.4 mg/kg 매주)은 탁산 대비 전체생존기간을 개선하지 못했습니다(중앙값 7.9개월 대 8.6개월, 위험비 1.15, 95% 신뢰구간 0.87–1.51). 3등급 이상 이상반응은 트라스투주맙 엠탄신군에서 더 적었고(60% 대 70%), 이상반응으로 인한 치료 중단은 비슷했습니다(14% 대 14%). 주요 3등급 이상 독성은 트라스투주맙 엠탄신군에서 빈혈과 혈소판감소증, 탁산군에서 호중구감소증이었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-JACOB", "trial": "G-JACOB", "papers": [ { "key": "P-JACOB18", "pmid": "30217672", "title": "Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30217672/", "doi": "10.1016/S1470-2045(18)30481-9", "errata": [] }, { "key": "P-JACOB", "pmid": "36066725", "title": "Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial.", "journal": "Gastric Cancer", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36066725/", "doi": "10.1007/s10120-022-01335-4", "errata": [] }, { "key": "P-JACOBbiomarker23", "pmid": "36413222", "title": "HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial.", "journal": "Clin Cancer Res", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36413222/", "doi": "10.1158/1078-0432.CCR-22-2533", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [ "G-HER2" ], "limits": "The end-of-study analysis is descriptive and does not change the primary result. The biomarker analysis is post hoc in a subset with sequenced samples; its resistance panel does not include CCNE1.", "label": "JACOB", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "First line", "population": "HER2-positive metastatic gastric or GEJ cancer", "claim": "Adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival at the primary analysis (HR 0.84, 95% CI 0.71–1.00). The later end-of-study analysis reported HR 0.85 (0.72–0.99) for OS and 0.73 for PFS. In a post hoc analysis of 327 sequenced samples, HER2 copy number above the median was associated with longer overall survival (20.3 vs. 13.0 months; HR 0.54, 0.42-0.72). A panel of candidate resistance alterations was positive in 51 (16%), with unadjusted HRs of 1.35 (0.98-1.86) for PFS and 1.43 (1.00-2.03) for OS; only HER2 copy number remained significant in multivariable models. These biomarkers were not associated with the treatment effect of pertuzumab.", "updated": "2026-10-06", "updatedBy": "Claude", "trialRecord": { "key": "G-JACOB", "nct": "NCT01774786", "acronym": "JACOB", "title": "A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 780, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2013-06-10", "lastUpdate": "2020-12-30", "url": "https://clinicaltrials.gov/study/NCT01774786" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival in the intention-to-treat population", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 780, "assessment": "not stated", "quote": "JACOB was a double-blind, placebo-controlled, randomised, multicentre, phase 3 trial … 780 eligible patients were randomly assigned to receive either pertuzumab plus trastuzumab and chemotherapy (pertuzumab group, n=388) or placebo plus trastuzumab and chemotherapy (control group, n=392)." }, "effect": { "measure": "HR", "value": 0.84, "ci_low": 0.71, "ci_high": 1, "ci_level": "95%", "p": "0.057", "endpoint": "Overall survival (primary analysis, Lancet Oncol 2018)", "quote": "overall survival was not significantly different between treatment groups (median overall survival 17·5 months [95% CI 16·2-19·3] in the pertuzumab group and 14·2 months [12·9-15·5] in the control group; hazard ratio 0·84 [95% CI 0·71-1·00]; p=0·057)" }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "End-of-study analysis (median follow-up ≥ 44.4 months)", "experimental_pct": 57, "control_pct": 48.6, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment.", "difference_pp": 8.4, "nnt": 12, "quote_note": "End-of-study analysis (Gastric Cancer 2023" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Seven (2%) in the control group; none in the pertuzumab group", "quote": "Serious adverse events occurred in 175 (45%) of 385 patients in the pertuzumab group and 152 (39%) of 388 patients in the control group. … The most common grade 3-5 adverse events were neutropenia (116 [30%] patients in the pertuzumab group vs 108 [28%] patients in the control group), anaemia (56 [15%] vs 65 [17%]), and diarrhoea (51 [13%] vs 25 [6%]). Treatment-related deaths occurred in seven (2%) patients in the control group; no treatment-related deaths occurred in the pertuzumab group." }, "takeaway_en": "In first-line HER2-positive metastatic gastric or gastro-oesophageal junction cancer, JACOB added pertuzumab or placebo to trastuzumab plus chemotherapy. The primary analysis did not show a significant overall survival improvement (median 17.5 vs 14.2 months; HR 0.84, 95% CI 0.71-1.00; p=0.057), and objective response at the end-of-study analysis was 57.0% vs 48.6%. Pertuzumab brought more serious adverse events (45% vs 39%) and more grade 3-5 diarrhoea (13% vs 6%).", "takeaway_ko": "JACOB 연구는 HER2 양성 전이성 위암 또는 위식도접합부암 1차 치료에서 트라스투주맙과 항암화학요법에 퍼투주맙 또는 위약을 추가하여 비교했습니다. 일차 분석에서 전체생존기간은 유의하게 개선되지 않았으며(중앙값 17.5개월 대 14.2개월, 위험비 0.84, 95% 신뢰구간 0.71-1.00, p=0.057), 최종 분석의 객관적 반응률은 57.0% 대 48.6%였습니다. 퍼투주맙군에서 중대한 이상반응(45% 대 39%)과 3-5등급 설사(13% 대 6%)가 더 많았습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-LOGiC", "trial": "G-LOGiC", "papers": [ { "key": "P-LOGiC", "pmid": "26628478", "title": "Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.", "journal": "J Clin Oncol", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26628478/", "doi": "10.1200/JCO.2015.62.6598", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [ "G-HER2" ], "limits": "", "label": "LOGiC", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "First line", "population": "HER2-amplified gastric, esophageal or GEJ adenocarcinoma", "claim": "Lapatinib plus capecitabine and oxaliplatin: overall survival 12.2 vs 10.5 months, not significantly different (HR 0.91, 0.73–1.12).", "trialRecord": { "key": "G-LOGiC", "nct": "NCT00680901", "acronym": null, "title": "LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 545, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2008-06-04", "lastUpdate": "2025-08-07", "url": "https://clinicaltrials.gov/study/NCT00680901" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 545, "assessment": "not stated", "quote": "Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. … A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population." }, "effect": { "measure": "HR", "value": 0.91, "ci_low": 0.73, "ci_high": 1.12, "ci_level": "95%", "p": null, "endpoint": "Overall survival", "quote": "Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12)." }, "landmark": [ { "endpoint": "Response rate", "timepoint": "best overall response (no fixed time point stated)", "experimental_pct": 53, "control_pct": 39, "higher_is_better": true, "experimental_arm": "Lapatinib + CapeOx", "control_arm": "Placebo + CapeOx", "quote": "Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031).", "difference_pp": 14, "nnt": 8, "quote_note": "J Clin Oncol 2016, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "There were increased toxicities in the lapatinib arm, particularly diarrhea." }, "takeaway_en": "In previously untreated HER2-amplified advanced gastric, esophageal or gastroesophageal junction adenocarcinoma, adding lapatinib to capecitabine and oxaliplatin did not significantly improve overall survival (median 12.2 vs 10.5 months; HR 0.91, 95% CI 0.73 to 1.12), although response rates were higher (53% vs 39%). The trade-off was increased toxicity in the lapatinib arm, particularly diarrhea; the abstract gives no grade 3 or higher rates.", "takeaway_ko": "이전에 치료받지 않은 HER2 증폭 진행성 위암, 식도암 또는 위식도접합부 선암 환자에서 카페시타빈·옥살리플라틴에 라파티닙을 추가해도 전체생존기간은 유의하게 개선되지 않았으나(중앙값 12.2개월 대 10.5개월; HR 0.91, 95% CI 0.73–1.12) 반응률은 더 높았습니다(53% 대 39%). 라파티닙군에서는 독성, 특히 설사가 증가했으며 초록에는 3등급 이상 이상반응 비율이 제시되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TyTAN", "trial": "G-TyTAN", "papers": [ { "key": "P-TyTAN", "pmid": "24868024", "title": "Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study.", "journal": "J Clin Oncol", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24868024/", "doi": "10.1200/JCO.2013.53.6136", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [ "G-HER2" ], "limits": "", "label": "TyTAN", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Second line", "population": "HER2-amplified advanced gastric cancer in Asian populations", "claim": "Lapatinib plus paclitaxel: overall survival 11.0 vs 8.9 months (P = .1044); no significant difference in PFS.", "trialRecord": { "key": "G-TyTAN", "nct": "NCT00486954", "acronym": null, "title": "Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 273, "sponsor": "GlaxoSmithKline", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2007-07", "lastUpdate": "2013-06-20", "url": "https://clinicaltrials.gov/study/NCT00486954" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 261, "assessment": "not stated", "quote": "TyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m(2) or paclitaxel alone." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": ".1044", "endpoint": "Overall survival (median 11.0 vs 8.9 months; no hazard ratio reported in abstract)", "quote": "Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%)." }, "takeaway_en": "In Asian patients with HER2 FISH-positive advanced gastric cancer receiving second-line therapy, adding lapatinib to weekly paclitaxel gave a median overall survival of 11.0 versus 8.9 months, which was not statistically significant (P = .1044; no hazard ratio reported in the abstract), with no significant difference in median PFS (5.4 v 4.4 months). Response rates were higher with the combination (odds ratio 3.85), and adverse events of any grade occurred in nearly all patients in both arms (100% v 98%); grade 3 or higher rates were not reported in the abstract.", "takeaway_ko": "2차 치료를 받는 HER2 FISH 양성 진행성 위암 아시아인 환자에서 주 1회 파클리탁셀에 라파티닙을 추가한 결과, 전체생존기간 중앙값은 11.0개월 대 8.9개월이었으나 통계적으로 유의하지 않았습니다(P = .1044, 초록에 위험비 미보고). 무진행생존기간 중앙값도 유의한 차이가 없었습니다(5.4개월 대 4.4개월). 병용군에서 반응률이 더 높았고(오즈비 3.85), 모든 등급의 이상반응은 두 군 모두 거의 전원에서 발생했습니다(100% 대 98%). 3등급 이상 이상반응 비율은 초록에 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "no confidence interval for the primary effect in the abstract", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN811", "trial": "G-KN811", "papers": [ { "key": "P-KN811a", "pmid": "34912120", "title": "The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer.", "journal": "Nature", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34912120/", "doi": "10.1038/s41586-021-04161-3", "errata": [] }, { "key": "P-KN811b", "pmid": "37871604", "title": "Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial.", "journal": "Lancet", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37871604/", "doi": "10.1016/S0140-6736(23)02033-0", "errata": [] }, { "key": "P-KN811OS", "pmid": "39282917", "title": "Pembrolizumab in HER2-Positive Gastric Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39282917/", "doi": "10.1056/NEJMc2408121", "errata": [] }, { "key": "P-KN811FDA", "pmid": "41790455", "title": "FDA Approval Summary: Pembrolizumab for the Treatment of HER2-Positive Gastric Cancer.", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41790455/", "doi": "10.1158/1078-0432.CCR-25-3726", "errata": [] } ], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [ "ERBB2", "PDCD1" ], "biomarkers": [ "BM-HER2-G", "BM-PDL1-CPS" ], "subtypes": [ "G-HER2", "G-PDL1" ], "limits": "Applies only to first-line unresectable/metastatic HER2-positive gastric/GEJ adenocarcinoma; no inference to HER2-negative disease or other lines/settings. CPS subgroups were exploratory; the CPS<1 estimate is from ~15% of patients with wide CI spanning benefit and harm, so does not prove harm or absence of effect. Safety is from the 2023 interim treated population (350 vs 346): grade ≥3 treatment-related events 58% vs 51%; treatment-related deaths 1% each. The original-trial final-OS correspondence (PMID:39282917) has no abstract; final OS numbers here are from the FDA-authored regulatory summary of the same KEYNOTE-811 trial, not a new trial or independent validation.", "label": "KEYNOTE-811", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "HER2-positive metastatic gastric or GEJ adenocarcinoma", "claim": "In the randomized, double-blind KEYNOTE-811 trial in previously untreated unresectable/metastatic HER2-positive gastric/GEJ adenocarcinoma (698 randomized: 350 to pembrolizumab and 348 to placebo, each with trastuzumab plus fluoropyrimidine-platinum), the final median overall survival reported in the FDA regulatory summary was 20.0 months [95% CI 17.8-22.1] vs 16.8 months [14.9-18.7]; HR 0.80 [0.67-0.94], P=0.004. Earlier readouts from the same trial were an ORR of 74.4% vs 51.9% at the first interim analysis (first 264 patients, P=0.00006) and a median PFS of 10.0 mo [8.6-11.7] vs 8.1 mo [7.0-8.5] at the second interim analysis (median follow-up ~28.3-28.5 mo); HR 0.72 [0.60-0.87], P=0.0002. Exploratory final OS by PD-L1 CPS: CPS≥1 (~85%) HR 0.79 [0.66-0.95]; CPS<1 (~15%) HR 1.10 [0.72-1.68].", "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "trialRecord": { "key": "G-KN811", "nct": "NCT03615326", "acronym": null, "title": "Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 738, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2018-10-05", "lastUpdate": "2026-08-26", "url": "https://clinicaltrials.gov/study/NCT03615326" }, "sources": 6, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Dual primary endpoints: progression-free survival and overall survival (intention to treat); final overall survival reported in the FDA summary", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 698, "assessment": "not stated", "quote": "randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study … 698 patients were assigned to pembrolizumab (n=350) or placebo (n=348)." }, "effect": { "measure": "HR", "value": 0.8, "ci_low": 0.67, "ci_high": 0.94, "ci_level": "95%", "p": "0.004", "endpoint": "Overall survival (final analysis)", "quote": "The final overall survival (OS) analysis demonstrated a clinically meaningful improvement, with a median OS of 20.0 months [95% confidence interval (CI), 17.8-22.1] and 16.8 months (95% CI, 14.9-18.7) in the pembrolizumab and placebo arms, respectively [hazard ratio (HR), 0.80 (95% CI, 0.67-0.94); P = 0.004]." }, "landmark": [ { "endpoint": "Objective response rate (first 264 patients randomized, first interim analysis)", "timepoint": "First interim analysis", "experimental_pct": 74.4, "control_pct": 51.9, "higher_is_better": true, "experimental_arm": "Pembrolizumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "Accelerated approval (AA) was granted based on the overall response rate (ORR) in the first 264 patients randomized, showing a statistically significant improvement with pembrolizumab (74.4% vs. 51.9%, P = 0.00006).", "difference_pp": 22.5, "nnt": 5, "quote_note": "FDA summary 2026; only reported ORR figures" } ], "harms": { "grade3plus_experimental_pct": 58, "grade3plus_control_pct": 51, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "four (1%) in the pembrolizumab group and three (1%) in the placebo group", "quote": "Grade 3 or worse treatment-related adverse events occurred in 204 (58%) of 350 patients in the pembrolizumab group versus 176 (51%) of 346 patients in the placebo group. Treatment-related adverse events that led to death occurred in four (1%) patients in the pembrolizumab group and three (1%) in the placebo group." }, "takeaway_en": "In previously untreated unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, KEYNOTE-811 compared pembrolizumab with placebo, each added to trastuzumab plus fluoropyrimidine-platinum chemotherapy. Objective response was 74.4% vs 51.9% in the first 264 patients, and final overall survival favored pembrolizumab (HR 0.80, median 20.0 vs 16.8 months), with benefit seemingly confined to PD-L1 CPS ≥1 (HR 0.79; CPS <1 HR 1.10); grade 3 or worse treatment-related adverse events occurred in 58% vs 51%.", "takeaway_ko": "이전 치료를 받지 않은 절제 불가능 또는 전이성 HER2 양성 위암·위식도접합부 선암 환자에서, KEYNOTE-811은 트라스투주맙과 플루오로피리미딘-백금 항암화학요법에 펨브롤리주맙 또는 위약을 추가하여 비교하였다. 첫 264명에서 객관적 반응률은 74.4% 대 51.9%였고, 최종 전체생존은 펨브롤리주맙군에서 우세하였다(HR 0.80, 중앙값 20.0개월 대 16.8개월). 다만 이 이득은 PD-L1 CPS ≥1 환자에 국한된 것으로 보였으며(HR 0.79; CPS <1은 HR 1.10), 3등급 이상 치료 관련 이상반응은 58% 대 51%에서 발생하였다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-HERIZON", "trial": "G-HERIZON", "papers": [ { "key": "P-HERIZON", "pmid": "42202319", "title": "Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42202319/", "doi": "10.1056/NEJMoa2517729", "errata": [] } ], "pages": [], "targets": [ "ERBB2", "PDCD1" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "Published 2026; not yet reflected in the NCI PDQ page saved on 2026-09-28.", "label": "HERIZON-GEA-01", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "Centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma", "claim": "Zanidatamab plus chemotherapy with or without tislelizumab vs trastuzumab plus chemotherapy: median PFS 12.4 and 12.4 vs 8.1 months (HR 0.63 and 0.65); OS 26.4 vs 19.2 months with the tislelizumab triplet (HR 0.72).", "trialRecord": { "key": "G-HERIZON", "nct": "NCT05152147", "acronym": "HERIZON-GEA-01", "title": "A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 920, "sponsor": "Jazz Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [ "BeOne Medicines LTD", "BeOne Pharmaceutical Co., Ltd." ], "hasResults": false, "start": "2021-12-02", "lastUpdate": "2026-10-20", "url": "https://clinicaltrials.gov/study/NCT05152147" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival and overall survival (two primary end points)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival." }, "effect": { "measure": "HR", "value": 0.63, "ci_low": 0.51, "ci_high": 0.78, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival, zanidatamab-tislelizumab-chemotherapy vs trastuzumab-chemotherapy", "quote": "hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 83.3, "grade3plus_control_pct": 74.5, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The incidence of grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively." }, "takeaway_en": "In previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma, zanidatamab plus chemotherapy with or without tislelizumab was compared with trastuzumab plus chemotherapy. Progression-free survival was longer with both zanidatamab regimens (HR 0.63 with tislelizumab and 0.65 without). At this interim analysis, overall survival was longer only with the tislelizumab triplet (HR 0.72; median 26.4 vs. 19.2 months). Grade 3 or higher adverse events occurred in 83.3% with the triplet, 73.8% with zanidatamab-chemotherapy and 74.5% with trastuzumab-chemotherapy, and diarrhea was more frequent with zanidatamab (24.8% and 20.0% vs. 12.9%).", "takeaway_ko": "이전 치료력이 없고 중앙 검사로 확인된 HER2 양성 진행성 위식도 선암 환자에서 zanidatamab+항암화학요법(tislelizumab 병용 또는 비병용)을 trastuzumab+항암화학요법과 비교했습니다. 무진행생존기간은 두 zanidatamab 요법 모두에서 연장되었습니다(위험비: tislelizumab 병용 0.63, 비병용 0.65). 이번 중간분석에서 전체생존기간은 tislelizumab 병용 3제 요법에서만 연장되었습니다(위험비 0.72, 중앙값 26.4개월 대 19.2개월). 3등급 이상 이상반응은 3제 요법 83.3%, zanidatamab+항암화학요법 73.8%, trastuzumab+항암화학요법 74.5%에서 발생했으며, 설사는 zanidatamab 군에서 더 흔했습니다(24.8% 및 20.0% 대 12.9%).", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-GASTHER3", "trial": null, "papers": [ { "key": "P-GASTHER3", "pmid": "30386954", "title": "Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3).", "journal": "Gastric Cancer", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30386954/", "doi": "10.1007/s10120-018-0891-1", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G", "BM-HER2HET" ], "subtypes": [ "G-HER2" ], "limits": "Single study, 48 patients.", "label": "GASTHER3", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "After first-line trastuzumab", "population": "48 HER2-positive advanced gastric cancer patients with paired biopsies", "claim": "14 patients (29.1%) lost HER2 positivity on post-progression biopsy (10 IHC 0/1+, 4 IHC 2+/ISH−). ISH-defined genetic heterogeneity rose from 2.9% at baseline to 21.9% at the second biopsy.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2loss16", "trial": null, "papers": [ { "key": "P-HER2lossP", "pmid": "27578417", "title": "HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: Implication for further clinical research.", "journal": "Int J Cancer", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27578417/", "doi": "10.1002/ijc.30408", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "22 patients.", "label": "HER2 loss after trastuzumab (2016)", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "After trastuzumab", "population": "22 HER2-positive gastric or GEJ cancer patients (IHC 3+ 14, IHC 2+ 8)", "claim": "Loss of HER2 positivity was observed in 32% of post-trastuzumab samples.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-Janjigian18", "trial": null, "papers": [ { "key": "P-Janjigian18", "pmid": "29122777", "title": "Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.", "journal": "Cancer Discov", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29122777/", "doi": "10.1158/2159-8290.CD-17-0787", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "", "label": "Esophagogastric genomic predictors", "program": "gastric", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "Esophagogastric cancer, prospective sequencing", "claim": "ERBB2 amplification level by sequencing predicted trastuzumab benefit. Intrinsic or acquired trastuzumab resistance was associated with selection of a subclone lacking ERBB2 amplification, with ERBB2 exon 16 deletion, and with co-mutations in the RTK, RAS and PI3K pathways.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-VIKTORY", "trial": "G-VIKTORY", "papers": [ { "key": "P-VIKTORY", "pmid": "31315834", "title": "Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial.", "journal": "Cancer Discov", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31315834/", "doi": "10.1158/2159-8290.CD-19-0442", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Screening protocol record; efficacy per arm not curated here.", "label": "VIKTORY", "program": "gastric", "kind": "single-arm", "level": "clinical", "result": "descriptive", "population": "Metastatic gastric cancer, umbrella screening", "claim": "772 patients enrolled; sequencing succeeded in 715 (92.6%); 14.7% received biomarker-assigned treatment when screening was linked to parallel matched trials.", "trialRecord": { "key": "G-VIKTORY", "nct": "NCT02299648", "acronym": null, "title": "The Screening Protocol for The VIKTORY Trial", "status": "COMPLETED", "phases": [ "NA" ], "enrollment": 651, "sponsor": "Samsung Medical Center", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2014-07-25", "lastUpdate": "2022-06-15", "url": "https://clinicaltrials.gov/study/NCT02299648" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-TCGASTAD", "trial": null, "papers": [ { "key": "P-TCGASTAD", "pmid": "25079317", "title": "Comprehensive molecular characterization of gastric adenocarcinoma.", "journal": "Nature", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25079317/", "doi": "10.1038/nature13480", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-MSI", "BM-EBV" ], "subtypes": [ "G-TCGA" ], "limits": "", "label": "TCGA gastric", "program": "gastric", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "Gastric adenocarcinoma, primary resections", "claim": "Proposed four molecular subtypes: EBV-positive (recurrent PIK3CA mutations, DNA hypermethylation, JAK2/CD274/PDCD1LG2 amplification), microsatellite unstable, genomically stable, and chromosomally unstable.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-SPOTLIGHT", "trial": "G-SPOTLIGHT", "papers": [ { "key": "P-SPOTLIGHT", "pmid": "37068504", "title": "Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.", "journal": "Lancet", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37068504/", "doi": "10.1016/S0140-6736(23)00620-7", "errata": [ { "pmid": "37481269", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/37481269/", "reviewed": true, "unresolvedIdentifier": false }, { "pmid": "38101428", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/38101428/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-ZolbePRO", "pmid": "39146670", "title": "Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials.", "journal": "ESMO Open", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39146670/", "doi": "10.1016/j.esmoop.2024.103663", "errata": [] }, { "key": "P-ZolbeNV", "pmid": "41741112", "title": "Impact and effective management of nausea/vomiting on patients treated with zolbetuximab + chemotherapy: insights from the phase III SPOTLIGHT and GLOW studies.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41741112/", "doi": "10.1016/j.esmoop.2025.105931", "errata": [] } ], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "subtypes": [ "G-CLDN" ], "limits": "The overall trial findings do not establish a separate PFS or OS benefit in gastro-oesophageal junction adenocarcinoma; the publisher correction states that this subgroup was too small for such conclusions. The saved PubMed abstract retains superseded wording that labels nausea, vomiting and decreased appetite as the most common severe adverse events; the corrected publisher abstract describes these as the most common all-grade adverse events. The corrections also revise appendix references, subgroup-figure and adverse-event-table details. The existing overall efficacy estimates are unchanged. The corrected appendix and underlying patient data were not independently audited. The same-trial PRO follow-up reported maintained measured quality of life and similar deterioration outcomes; these trends do not establish equivalence or absence of harm. Questionnaire compliance used patients expected to respond while on treatment or follow-up as its denominator, not all-randomized retention. Missing PRO assessments were not imputed. Primary deterioration analyses censored death; sensitivity analyses treated death as an event. Selected methods were reviewed; supplementary tables and underlying missing data were not audited. The ad hoc exploratory survival report censored patients whose nausea/vomiting led to inadequate exposure or early discontinuation. This post-randomization selection may bias comparisons and does not establish causal antiemetic survival benefit. The selected methods do not specify the exact censoring timestamp; day-63 inclusion remains unclear from the reported early-discontinuation wording. Antiemetic subgroup observations are not interpreted as randomized antiemetic comparisons. Primary trial efficacy estimates are retained; these follow-ups add no independent trial or RISCON patient-record analysis.", "label": "SPOTLIGHT", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "CLDN18.2-positive (≥75% of tumour cells with moderate-to-strong membranous CLDN18 staining), HER2-negative", "claim": "Zolbetuximab plus mFOLFOX6 vs placebo: PFS HR 0.75 and OS HR 0.75 (0.60–0.94); median PFS 10.61 vs 8.67 months (NCI PDQ).", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex source check and integration", "trialRecord": { "key": "G-SPOTLIGHT", "nct": "NCT03504397", "acronym": "Spotlight", "title": "A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 565, "sponsor": "Astellas Pharma Global Development, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2018-06-21", "lastUpdate": "2026-10-20", "url": "https://clinicaltrials.gov/study/NCT03504397" }, "sources": 5, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by independent review committee in all randomly assigned patients", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 565, "assessment": "blinded independent central review", "quote": "SPOTLIGHT is a global, randomised, placebo-controlled, double-blind, phase 3 trial that enrolled patients from 215 centres in 20 countries. … The primary endpoint was progression-free survival assessed by independent review committee in all randomly assigned patients. … 565 patients were randomly assigned to receive either zolbetuximab plus mFOLFOX6 (283 patients; the zolbetuximab group) or placebo plus mFOLFOX6 (282 patients; the placebo group)." }, "effect": { "measure": "HR", "value": 0.75, "ci_low": 0.6, "ci_high": 0.94, "ci_level": "95%", "p": "0·0066", "endpoint": "Progression-free survival (independent review committee)", "quote": "Zolbetuximab treatment showed a significant reduction in the risk of disease progression or death compared with placebo (hazard ratio [HR] 0·75, 95% CI 0·60-0·94; p=0·0066). The median progression-free survival was 10·61 months (95% CI 8·90-12·48) in the zolbetuximab group versus 8·67 months (8·21-10·28) in the placebo group. Zolbetuximab treatment also showed a significant reduction in the risk of death versus placebo (HR 0·75, 95% CI 0·60-0·94; p=0·0053)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 87, "grade3plus_control_pct": 78, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "five (2%) patients in the zolbetuximab group versus four (1%) patients in the placebo group", "quote": "Treatment-emergent grade 3 or worse adverse events occurred in 242 (87%) of 279 patients in the zolbetuximab group versus 216 (78%) of 278 patients in the placebo group. The most common grade 3 or worse adverse events were nausea, vomiting, and decreased appetite. Treatment-related deaths occurred in five (2%) patients in the zolbetuximab group versus four (1%) patients in the placebo group." }, "takeaway_en": "In previously untreated CLDN18.2-positive, HER2-negative advanced gastric or gastro-oesophageal junction adenocarcinoma, adding zolbetuximab to mFOLFOX6 lowered the risk of progression or death compared with placebo plus mFOLFOX6 (HR 0.75; median PFS 10.61 vs 8.67 months). It also lowered the risk of death (OS HR 0.75), but grade 3 or worse adverse events were more frequent (87% vs 78%), mainly nausea, vomiting and decreased appetite.", "takeaway_ko": "치료 경험이 없는 CLDN18.2 양성, HER2 음성 진행성 위암 또는 위식도접합부 선암 환자에서 mFOLFOX6에 졸베툭시맙을 추가하자 위약 + mFOLFOX6 대비 질병 진행 또는 사망 위험이 낮아졌습니다(위험비 0.75, 무진행생존기간 중앙값 10.61개월 대 8.67개월). 사망 위험도 감소했으나(전체생존 위험비 0.75), 3등급 이상 이상반응은 더 많았으며(87% 대 78%) 주로 오심, 구토, 식욕 감소였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-GLOW", "trial": "G-GLOW", "papers": [ { "key": "P-GLOW", "pmid": "37524953", "title": "Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.", "journal": "Nat Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37524953/", "doi": "10.1038/s41591-023-02465-7", "errata": [] }, { "key": "P-ZolbePRO", "pmid": "39146670", "title": "Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials.", "journal": "ESMO Open", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39146670/", "doi": "10.1016/j.esmoop.2024.103663", "errata": [] }, { "key": "P-ZolbeNV", "pmid": "41741112", "title": "Impact and effective management of nausea/vomiting on patients treated with zolbetuximab + chemotherapy: insights from the phase III SPOTLIGHT and GLOW studies.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41741112/", "doi": "10.1016/j.esmoop.2025.105931", "errata": [] } ], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "subtypes": [ "G-CLDN" ], "limits": "The same-trial PRO follow-up reported maintained measured quality of life and similar deterioration outcomes; these trends do not establish equivalence or absence of harm. Questionnaire compliance used patients expected to respond while on treatment or follow-up as its denominator, not all-randomized retention. Missing PRO assessments were not imputed. Primary deterioration analyses censored death; sensitivity analyses treated death as an event. Selected methods were reviewed; supplementary tables and underlying missing data were not audited. The ad hoc exploratory survival report censored patients whose nausea/vomiting led to inadequate exposure or early discontinuation. This post-randomization selection may bias comparisons and does not establish causal antiemetic survival benefit. The selected methods do not specify the exact censoring timestamp; day-63 inclusion remains unclear from the reported early-discontinuation wording. Antiemetic subgroup observations are not interpreted as randomized antiemetic comparisons. Primary trial efficacy estimates are retained; these follow-ups add no independent trial or RISCON patient-record analysis.", "label": "GLOW", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "CLDN18.2-positive, HER2-negative", "claim": "Zolbetuximab plus CAPOX: PFS 8.21 vs 6.80 months (HR 0.687); OS 14.39 vs 12.16 months (HR 0.771).", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex source check and integration", "trialRecord": { "key": "G-GLOW", "nct": "NCT03653507", "acronym": "GLOW", "title": "A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW).", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 507, "sponsor": "Astellas Pharma Global Development, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2018-11-28", "lastUpdate": "2026-09-28", "url": "https://clinicaltrials.gov/study/NCT03653507" }, "sources": 5, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 507, "assessment": "not stated", "quote": "GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab … Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX." }, "effect": { "measure": "HR", "value": 0.687, "ci_low": 0.544, "ci_high": 0.866, "ci_level": "95%", "p": "0.0007", "endpoint": "Progression-free survival", "quote": "GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 72.8, "grade3plus_control_pct": 69.9, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%)." }, "takeaway_en": "In patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, first-line zolbetuximab plus CAPOX was compared with placebo plus CAPOX. Zolbetuximab improved progression-free survival (median 8.21 vs 6.80 months; HR 0.687) and overall survival (median 14.39 vs 12.16 months; HR 0.771), with similar rates of grade ≥3 adverse events (72.8% vs 69.9%), but nausea and vomiting were common, especially on the first infusion day, in a pooled SPOTLIGHT/GLOW analysis.", "takeaway_ko": "CLDN18.2 양성, HER2 음성 국소 진행성 절제 불가능 또는 전이성 위암 및 위식도접합부 선암 환자를 대상으로, 1차 치료로 졸베툭시맙+CAPOX와 위약+CAPOX를 비교하였다. 졸베툭시맙군에서 무진행생존기간(중앙값 8.21개월 대 6.80개월, HR 0.687)과 전체생존기간(중앙값 14.39개월 대 12.16개월, HR 0.771)이 개선되었다. 3등급 이상 이상반응 발생률은 비슷하였으나(72.8% 대 69.9%), SPOTLIGHT/GLOW 통합 분석에서 오심과 구토가 흔했으며 특히 첫 투여일에 많았다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CT041", "trial": "G-CT041", "papers": [ { "key": "P-CT041", "pmid": "40460847", "title": "Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial.", "journal": "Lancet", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40460847/", "doi": "10.1016/S0140-6736(25)00860-8", "errata": [] } ], "pages": [], "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "subtypes": [ "G-CLDN" ], "limits": "CLDN18.2 positivity threshold differs from the zolbetuximab trials. Open label.", "label": "Satri-cel CT041-ST-01", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Third line or later", "population": "CLDN18.2-positive (IHC ≥2+ in ≥40% of tumour cells), refractory to ≥2 lines, China", "claim": "CLDN18.2-specific CAR T cells vs physician's choice (2:1): median PFS 3.25 vs 1.77 months (HR 0.37). 69% of the satri-cel group had peritoneal metastasis.", "trialRecord": { "key": "G-CT041", "nct": "NCT04581473", "acronym": null, "title": "Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1", "PHASE2" ], "enrollment": 192, "sponsor": "CARsgen Therapeutics Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [ "Peking University Cancer Hospital & Institute", "Fudan University" ], "hasResults": false, "start": "2020-10-23", "lastUpdate": "2025-06-05", "url": "https://clinicaltrials.gov/study/NCT04581473" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by an independent review committee in the intention-to-treat population", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "open-label", "n_randomized": 156, "assessment": "blinded independent central review", "quote": "In this open-label, multicentre, randomised controlled trial conducted in China … were randomly allocated (2:1) to receive satri-cel or treatment of physician's choice (TPC). … The primary endpoint was progression-free survival, assessed by an independent review committee, in the intention-to-treat population. … 156 were randomly allocated to the satri-cel group (n=104) or TPC group (n=52)." }, "effect": { "measure": "HR", "value": 0.37, "ci_low": 0.24, "ci_high": 0.56, "ci_level": "95%", "p": "<0.0001 (one-sided log-rank)", "endpoint": "Progression-free survival (intention-to-treat)", "quote": "In the intention-to-treat population, median progression-free survival was 3·25 months (95% CI 2·86-4·53) in the satri-cel group and 1·77 months (1·61-2·04) in the TPC group (hazard ratio 0·37 [95% CI 0·24-0·56]; one-sided log-rank p<0·0001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 99, "grade3plus_control_pct": 63, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "In the safety analysis set (all patients who received at least one dose of study drug), grade 3 or higher treatment-emergent adverse events occurred in 87 (99%) of 88 patients in the satri-cel group and 30 (63%) of 48 patients in the TPC group. … Cytokine release syndrome occurred in 84 (95%) of 88 patients in the satri-cel group." }, "takeaway_en": "In Chinese patients with CLDN18.2-positive advanced gastric or gastro-oesophageal junction cancer refractory to at least two prior lines, the CLDN18.2-directed CAR T-cell therapy satri-cel improved progression-free survival compared with physician's choice of nivolumab, a taxane, irinotecan or apatinib (median 3.25 vs 1.77 months; HR 0.37, 95% CI 0.24-0.56) in this open-label phase 2 trial. Grade 3 or higher treatment-emergent adverse events occurred in 99% of treated patients with satri-cel versus 63% with physician's choice, mostly lymphocyte, white cell and neutrophil count decreases, and cytokine release syndrome occurred in 95% of satri-cel recipients.", "takeaway_ko": "CLDN18.2 양성이면서 2차 이상의 치료에 불응한 진행성 위암 또는 위식도접합부암 중국인 환자를 대상으로 한 공개 2상 무작위 시험입니다. CLDN18.2 표적 CAR-T 세포치료제 사트리셀(satri-cel)은 의사 선택 치료(니볼루맙, 탁산, 이리노테칸 또는 아파티닙)에 비해 무진행생존을 개선했습니다(중앙값 3.25개월 대 1.77개월; 위험비 0.37, 95% 신뢰구간 0.24-0.56). 투약받은 환자 중 3등급 이상 치료 관련 이상반응(TEAE)은 사트리셀군 99%, 의사 선택 치료군 63%에서 발생했으며, 주로 림프구·백혈구·호중구 감소였고, 사트리셀군의 95%에서 사이토카인 방출 증후군이 나타났습니다.", "certainty": { "level": "moderate", "reasons": [ "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CM649", "trial": "G-CM649", "papers": [ { "key": "P-CM649", "pmid": "34102137", "title": "First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.", "journal": "Lancet", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34102137/", "doi": "10.1016/S0140-6736(21)00797-2", "errata": [] }, { "key": "P-CM6493yr", "pmid": "38382001", "title": "First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38382001/", "doi": "10.1200/JCO.23.01601", "errata": [] } ], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-PDL1", "G-HER2NEG" ], "limits": "The published 3-year update (cutoff May 31, 2022; minimum follow-up 36.2 months) reported OS HR 0.70 (95% CI 0.61–0.81) and 36-month survival of 21% versus 10% in PD-L1 CPS ≥5, for nivolumab plus chemotherapy versus chemotherapy. Results in this update were not formally tested. The primary OS and PFS comparisons were in CPS ≥5; overall-population improvement does not establish benefit in each low-CPS subgroup. Grade 3/4 treatment-related adverse events occurred in 60% versus 45% of treated patients (n=782 versus n=767). Original primary-report estimates are retained above. This is follow-up of the same trial, not an independent replication or a new RISCON patient analysis.", "label": "CheckMate 649", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "HER2-negative advanced gastric, GEJ or esophageal adenocarcinoma", "claim": "Nivolumab plus chemotherapy: in patients with PD-L1 CPS ≥ 5 (the primary population), OS HR 0.71 and PFS HR 0.68; in all patients, OS 14.0 vs 11.3 months (HR 0.77, NCI PDQ).", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex source check and integration", "trialRecord": { "key": "G-CM649", "nct": "NCT02872116", "acronym": "CheckMate649", "title": "Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 2031, "sponsor": "Bristol-Myers Squibb", "sponsorClass": "INDUSTRY", "collaborators": [ "Ono Pharmaceutical Co., Ltd." ], "hasResults": true, "start": "2016-10-12", "lastUpdate": "2025-08-07", "url": "https://clinicaltrials.gov/study/NCT02872116" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS) and progression-free survival (PFS) by blinded independent central review in patients with PD-L1 CPS ≥5 (co-primary endpoints)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 1581, "assessment": "blinded independent central review", "quote": "In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649) … Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more … we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%])." }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.61, "ci_high": 0.81, "ci_level": "95%", "p": null, "endpoint": "Overall survival, PD-L1 CPS ≥5 (3-year update, 36.2-month minimum follow-up)", "quote": "With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81).", "quote_note": "P-CM6493yr (JCO 2024, 3-year update); The primary analysis (Lancet 2021) reported OS HR 0·71 (98·4% CI 0·59-0·86); p<0·0001." }, "landmark": [ { "endpoint": "Overall survival (PD-L1 CPS ≥5)", "timepoint": "36 months", "experimental_pct": 21, "control_pct": 10, "higher_is_better": true, "experimental_arm": "Nivolumab plus chemotherapy", "control_arm": "Chemotherapy alone", "quote": "21% versus 10% of patients were alive at 36 months, respectively", "difference_pp": 11, "nnt": 10, "quote_note": "P-CM6493yr (3-year update" }, { "endpoint": "Progression-free survival by BICR (PD-L1 CPS ≥5)", "timepoint": "36 months", "experimental_pct": 13, "control_pct": 8, "higher_is_better": true, "experimental_arm": "Nivolumab plus chemotherapy", "control_arm": "Chemotherapy alone", "quote": "the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively.", "difference_pp": 5, "nnt": 20, "quote_note": "P-CM6493yr (3-year update" }, { "endpoint": "Objective response rate by BICR (PD-L1 CPS ≥5)", "timepoint": "3-year update (36.2-month minimum follow-up)", "experimental_pct": 60, "control_pct": 45, "higher_is_better": true, "experimental_arm": "Nivolumab plus chemotherapy", "control_arm": "Chemotherapy alone", "quote": "The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy", "difference_pp": 15, "nnt": 7, "quote_note": "P-CM6493yr (3-year update" } ], "harms": { "grade3plus_experimental_pct": 59, "grade3plus_control_pct": 44, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "16 (2%) in the nivolumab plus chemotherapy group vs four (1%) in the chemotherapy alone group", "quote": "Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events … 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related.", "quote_note": "P-CM649 (Lancet 2021; these are grade 3-4 treatment-related adverse events, all treated patients" }, "takeaway_en": "In previously untreated, non-HER2-positive advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma with PD-L1 CPS ≥5, adding nivolumab to chemotherapy raised 36-month overall survival to 21% versus 10% with chemotherapy alone (OS HR 0.70) in the 3-year update. Grade 3-4 treatment-related adverse events were more common with nivolumab plus chemotherapy (59% vs 44%), and treatment-related deaths were 2% versus 1%.", "takeaway_ko": "이전에 치료받지 않은 HER2 비양성 진행성 위, 위식도접합부 또는 식도 선암 환자 중 PD-L1 CPS 5 이상인 환자에서, 3년 추적 결과 항암화학요법에 니볼루맙을 추가하면 36개월 전체생존율이 21%로, 항암화학요법 단독군의 10%보다 높았습니다(전체생존 위험비 0.70). 3~4등급 치료 관련 이상반응은 니볼루맙 병용군에서 더 흔했고(59% 대 44%), 치료 관련 사망은 2% 대 1%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN859", "trial": "G-KN859", "papers": [ { "key": "P-KN859", "pmid": "37875143", "title": "Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial.", "journal": "Lancet Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37875143/", "doi": "10.1016/S1470-2045(23)00515-6", "errata": [ { "pmid": "39637898", "title": "Correction to Lancet Oncol 2023; 24: 1181-95.", "url": "https://pubmed.ncbi.nlm.nih.gov/39637898/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-HER2NEG" ], "limits": "", "label": "KEYNOTE-859", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "HER2-negative advanced gastric or GEJ adenocarcinoma", "claim": "Pembrolizumab plus chemotherapy: ITT overall survival 12.9 vs 11.5 months (HR 0.78).", "trialRecord": { "key": "G-KN859", "nct": "NCT03675737", "acronym": null, "title": "Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1579, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2018-11-08", "lastUpdate": "2026-02-27", "url": "https://clinicaltrials.gov/study/NCT03675737" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival in the intention-to-treat population, and in populations with PD-L1 CPS ≥1 and CPS ≥10", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 1579, "assessment": "not stated", "quote": "KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. … 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789)." }, "effect": { "measure": "HR", "value": 0.78, "ci_low": 0.7, "ci_high": 0.87, "ci_level": "95%", "p": "p<0·0001", "endpoint": "Overall survival, ITT population (interim analysis)", "quote": "Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "eight (1%) pembrolizumab group vs 16 (2%) placebo group", "quote": "Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group." }, "takeaway_en": "In previously untreated HER2-negative advanced gastric or gastro-esophageal junction adenocarcinoma, adding pembrolizumab to fluoropyrimidine-platinum chemotherapy prolonged median overall survival from 11.5 to 12.9 months versus placebo (HR 0.78) at this interim analysis. Serious treatment-related adverse events were somewhat more frequent with pembrolizumab (23% vs 19%), while treatment-related deaths occurred in 1% vs 2%.", "takeaway_ko": "이전 치료력이 없는 HER2 음성 진행성 위암 또는 위식도접합부 선암 환자에서 플루오로피리미딘-백금 항암화학요법에 펨브롤리주맙을 추가하자, 중간 분석에서 위약 대비 전체생존기간 중앙값이 11.5개월에서 12.9개월로 연장되었습니다(위험비 0.78). 중대한 치료 관련 이상반응은 펨브롤리주맙군에서 다소 더 많았고(23% 대 19%), 치료 관련 사망은 1% 대 2%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RAT305", "trial": "G-RAT305", "papers": [ { "key": "P-RAT305", "pmid": "38806195", "title": "Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial.", "journal": "BMJ", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38806195/", "doi": "10.1136/bmj-2023-078876", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-TAP" ], "subtypes": [ "G-HER2NEG" ], "limits": "Uses the TAP score, not CPS. Tislelizumab is not listed in the NCI PDQ page saved on 2026-09-28.", "label": "RATIONALE-305", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line", "population": "Advanced gastric or GEJ adenocarcinoma", "claim": "Tislelizumab plus chemotherapy: in PD-L1 TAP ≥ 5% OS 17.2 vs 12.6 months (HR 0.74); also improved in all randomised patients at the final analysis (15.0 vs 12.9 months; HR 0.80, 95% CI 0.70 to 0.92; P=0.001). The PD-L1 TAP ≥ 5% result was from the interim analysis.", "trialRecord": { "key": "G-RAT305", "nct": "NCT03777657", "acronym": null, "title": "Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 997, "sponsor": "BeiGene", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2018-12-13", "lastUpdate": "2025-02-14", "url": "https://clinicaltrials.gov/study/NCT03777657" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 997, "assessment": "not stated", "quote": "Randomised, double blind, placebo controlled, phase 3 study. … Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496)." }, "effect": { "measure": "HR", "value": 0.8, "ci_low": 0.7, "ci_high": 0.92, "ci_level": "95%", "p": "P=0.001", "endpoint": "Overall survival in all randomised patients (final analysis)", "quote": "in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis))" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 54, "grade3plus_control_pct": 50, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm." }, "takeaway_en": "In 997 patients with previously untreated HER2-negative advanced gastric or gastro-oesophageal junction adenocarcinoma, adding tislelizumab to chemotherapy improved overall survival compared with placebo plus chemotherapy. In all randomised patients at the final analysis, median survival was 15.0 vs 12.9 months (HR 0.80, 95% CI 0.70 to 0.92). The interim analysis in PD-L1 TAP ≥5% patients showed 17.2 vs 12.6 months (HR 0.74). Grade 3 or worse treatment-related adverse events occurred in 54% vs 50% of patients.", "takeaway_ko": "이전에 치료받지 않은 HER2 음성 진행성 위암 또는 위식도접합부 선암 환자 997명에서, 항암화학요법에 티슬렐리주맙을 추가하자 위약+항암화학요법 대비 전체생존기간이 개선되었습니다. 전체 무작위배정 환자의 최종 분석에서 중앙 생존기간은 15.0개월 대 12.9개월이었습니다(위험비 0.80, 95% 신뢰구간 0.70~0.92). PD-L1 TAP ≥5% 환자의 중간 분석에서는 17.2개월 대 12.6개월이었습니다(위험비 0.74). 3등급 이상 치료 관련 이상반응은 54% 대 50%에서 발생했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-VESTIGE", "trial": null, "papers": [ { "key": "P-PM39542422", "pmid": "39542422", "title": "Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.", "journal": "Ann Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39542422/", "doi": "10.1016/j.annonc.2024.10.829", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "Open-label randomised phase II trial stopped early. Nivolumab plus ipilimumab replaced adjuvant chemotherapy rather than being added to it, so the trial does not test adding immunotherapy to adjuvant chemotherapy.", "label": "VESTIGE (EORTC 1707)", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Adjuvant, after neoadjuvant chemotherapy and resection", "population": "Gastric or oesophagogastric junction adenocarcinoma with ypN+ and/or R1 resection", "claim": "Adjuvant nivolumab plus ipilimumab vs adjuvant chemotherapy: median disease-free survival 11.4 vs 20.8 months (HR 1.55, 95% CI 1.07-2.25), favouring chemotherapy; recruitment was stopped early for futility and 195 patients were analysed.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival in the intent-to-treat population", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "2", "randomized": true, "blinding": "open-label", "n_randomized": 195, "assessment": "not stated", "quote": "VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. … The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy)." }, "effect": { "measure": "HR", "value": 1.55, "ci_low": 1.07, "ci_high": 2.25, "ci_level": "95%", "p": "one-sided P = 0.99", "endpoint": "Disease-free survival (nivolumab/ipilimumab vs chemotherapy)", "quote": "Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99)." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "12 months", "experimental_pct": 47.1, "control_pct": 64, "higher_is_better": true, "experimental_arm": "Adjuvant nivolumab plus ipilimumab", "control_arm": "Adjuvant chemotherapy (same regimen as neoadjuvant)", "quote": "The 12-month disease-free survival rates were 47.1% and 64.0%, respectively.", "difference_pp": -16.9, "nnt": null, "nnt_label": "favours control", "quote_note": "Single paper; final analysis at median follow-up 25.3 months.", "nnh": 6 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "There were no toxicity concerns or excess early discontinuations." }, "takeaway_en": "In patients with gastric or oesophagogastric junction adenocarcinoma who still had positive lymph nodes (ypN+) and/or positive margins (R1) after neoadjuvant chemotherapy and surgery, this open-label phase II trial compared adjuvant nivolumab plus ipilimumab with adjuvant chemotherapy. It was stopped early for futility, and 12-month disease-free survival was worse with immunotherapy: 47.1% versus 64.0% (HR 1.55, 95% CI 1.07-2.25). The abstract reports no toxicity concerns and no excess early discontinuations, but gives no adverse-event rates.", "takeaway_ko": "선행항암화학요법과 수술 후에도 림프절 양성(ypN+) 및/또는 절제연 양성(R1)인 위 또는 위식도접합부 선암 환자에서, 이 공개 2상 시험은 보조 nivolumab+ipilimumab 병용요법과 보조 항암화학요법을 비교했습니다. 시험은 무익성으로 조기 중단되었으며, 12개월 무병생존율은 면역요법군이 47.1%로 항암화학요법군 64.0%보다 낮았습니다(위험비 1.55, 95% 신뢰구간 1.07-2.25). 초록에는 독성 우려나 조기 중단 증가가 없었다고만 기술되어 있고, 이상반응 발생률 수치는 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN061", "trial": "G-KN061", "papers": [ { "key": "P-KN061", "pmid": "29880231", "title": "Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial.", "journal": "Lancet", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29880231/", "doi": "10.1016/S0140-6736(18)31257-1", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-PDL1" ], "limits": "", "label": "KEYNOTE-061", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Second line", "population": "PD-L1 CPS ≥ 1 advanced gastric or GEJ cancer", "claim": "Pembrolizumab vs paclitaxel: OS 9.1 vs 8.3 months (HR 0.82, 0.66–1.03), not significant; PFS worse with pembrolizumab (HR 1.27).", "trialRecord": { "key": "G-KN061", "nct": "NCT02370498", "acronym": null, "title": "A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 592, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-05-11", "lastUpdate": "2022-06-06", "url": "https://clinicaltrials.gov/study/NCT02370498" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival and progression-free survival (co-primary) in patients with PD-L1 CPS of 1 or higher", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 395, "assessment": "not stated", "quote": "This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. [ … ] Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. [ … ] 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel.", "quote_note": "n_randomized refers to the CPS ≥1 primary analysis population; 592 enrolled overall" }, "effect": { "measure": "HR", "value": 0.82, "ci_low": 0.66, "ci_high": 1.03, "ci_level": "95%", "p": "one-sided p=0·0421 (significance threshold p=0·0135, one-sided)", "endpoint": "Overall survival (PD-L1 CPS ≥1)", "quote": "Median overall survival was 9·1 months (95% CI 6·2-10·7) with pembrolizumab and 8·3 months (7·6-9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66-1·03; one-sided p=0·0421)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 14, "grade3plus_control_pct": 35, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "In the total population, grade 3-5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel." }, "takeaway_en": "In patients with PD-L1 CPS ≥1 advanced gastric or gastro-oesophageal junction cancer that progressed after platinum and fluoropyrimidine chemotherapy, second-line pembrolizumab did not significantly improve overall survival compared with paclitaxel (median 9.1 vs 8.3 months; HR 0.82, 95% CI 0.66–1.03), and progression-free survival was worse with pembrolizumab (median 1.5 vs 4.1 months; HR 1.27). Pembrolizumab caused fewer grade 3–5 treatment-related adverse events (14% vs 35% in the total treated population).", "takeaway_ko": "백금 및 플루오로피리미딘 1차 항암화학요법 후 진행한 PD-L1 CPS 1 이상 진행성 위암 또는 위식도접합부암 환자에서, 2차 치료로 펨브롤리주맙은 파클리탁셀 대비 전체생존기간을 유의하게 개선하지 못했습니다(중앙값 9.1개월 대 8.3개월; 위험비 0.82, 95% 신뢰구간 0.66–1.03). 무진행생존기간은 펨브롤리주맙군에서 오히려 짧았습니다(중앙값 1.5개월 대 4.1개월; 위험비 1.27). 3–5등급 치료 관련 이상반응은 펨브롤리주맙군에서 더 적었습니다(전체 치료 집단에서 14% 대 35%).", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN062", "trial": "G-KN062", "papers": [ { "key": "P-KN062", "pmid": "32880601", "title": "Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial.", "journal": "JAMA Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32880601/", "doi": "10.1001/jamaoncol.2020.3370", "errata": [] } ], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-PDL1" ], "limits": "", "label": "KEYNOTE-062", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First line", "population": "PD-L1 CPS ≥ 1 advanced gastric or GEJ cancer", "claim": "Pembrolizumab monotherapy was non-inferior to chemotherapy for OS (10.6 vs 11.1 months) but not superior; per NCI PDQ, final results did not show superiority of pembrolizumab or pembrolizumab plus chemotherapy over chemotherapy.", "trialRecord": { "key": "G-KN062", "nct": "NCT02494583", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 763, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-07-31", "lastUpdate": "2023-04-13", "url": "https://clinicaltrials.gov/study/NCT02494583" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 763, "assessment": "not stated", "quote": "The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater … Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy … , or chemotherapy plus placebo, every 3 weeks." }, "effect": { "measure": "HR", "value": 0.91, "ci_low": 0.69, "ci_high": 1.18, "ci_level": "99.2%", "p": null, "endpoint": "Overall survival, pembrolizumab vs chemotherapy, PD-L1 CPS of 1 or greater (non-inferiority; 99.2% CI)", "quote": "At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 17, "grade3plus_control_pct": 69, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively." }, "takeaway_en": "In untreated advanced gastric or gastroesophageal junction cancer with PD-L1 CPS of 1 or greater, first-line pembrolizumab alone was non-inferior but not superior to cisplatin plus fluoropyrimidine chemotherapy for overall survival (median 10.6 vs 11.1 months; HR 0.91, 99.2% CI 0.69-1.18), and adding pembrolizumab to chemotherapy was also not superior to chemotherapy alone. Grade 3 to 5 treatment-related adverse events occurred in 17% with pembrolizumab alone versus 69% with chemotherapy, and in 73% with pembrolizumab plus chemotherapy.", "takeaway_ko": "PD-L1 CPS 1 이상인 치료 경험이 없는 진행성 위암 또는 위식도접합부암 환자에서, 1차 치료로 펨브롤리주맙 단독요법은 시스플라틴과 플루오로피리미딘 병용 항암화학요법에 비해 전체생존기간에서 비열등했으나 우월하지는 않았습니다(중앙값 10.6개월 대 11.1개월; 위험비 0.91, 99.2% 신뢰구간 0.69-1.18). 항암화학요법에 펨브롤리주맙을 추가한 병용요법도 항암화학요법 단독보다 우월하지 않았습니다. 3-5등급 치료 관련 이상반응은 펨브롤리주맙 단독군 17%, 항암화학요법군 69%, 펨브롤리주맙 병용 항암화학요법군 73%에서 발생했습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RAINBOW", "trial": "G-RAINBOW", "papers": [ { "key": "P-RAINBOW", "pmid": "25240821", "title": "Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.", "journal": "Lancet Oncol", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25240821/", "doi": "10.1016/S1470-2045(14)70420-6", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "", "label": "RAINBOW", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Second line", "population": "Previously treated advanced gastric or GEJ adenocarcinoma", "claim": "Ramucirumab plus paclitaxel: OS 9.6 vs 7.4 months (HR 0.807).", "trialRecord": { "key": "G-RAINBOW", "nct": "NCT01170663", "acronym": "RAINBOW", "title": "A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 665, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2010-12", "lastUpdate": "2019-09-18", "url": "https://clinicaltrials.gov/study/NCT01170663" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 665, "assessment": "not stated", "quote": "This randomised, placebo-controlled, double-blind, phase 3 trial was done at 170 centres in 27 countries … 665 patients were randomly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel." }, "effect": { "measure": "HR", "value": 0.807, "ci_low": 0.678, "ci_high": 0.962, "ci_level": "95%", "p": "p=0·017", "endpoint": "Overall survival", "quote": "Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group (median 9·6 months [95% CI 8·5-10·8] vs 7·4 months [95% CI 6·3-8·4], hazard ratio 0·807 [95% CI 0·678-0·962]; p=0·017)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 or higher adverse events that occurred in more than 5% of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia (133 [41%] of 327 vs 62 [19%] of 329), leucopenia (57 [17%] vs 22 [7%]), hypertension (46 [14%] vs eight [2%]), fatigue (39 [12%] vs 18 [5%]), anaemia (30 [9%] vs 34 [10%]), and abdominal pain (20 [6%] vs 11 [3%]). The incidence of grade 3 or higher febrile neutropenia was low in both groups (ten [3%] vs eight [2%])." }, "takeaway_en": "In patients with advanced gastric or gastro-oesophageal junction adenocarcinoma that progressed on or within 4 months of first-line platinum plus fluoropyrimidine chemotherapy, adding ramucirumab to paclitaxel improved overall survival versus placebo plus paclitaxel (median 9.6 vs 7.4 months; hazard ratio 0.807). The trade-off was more grade 3 or higher toxicity, notably neutropenia (41% vs 19%), leucopenia (17% vs 7%), hypertension (14% vs 2%) and fatigue (12% vs 5%), while grade 3 or higher febrile neutropenia stayed low in both arms (3% vs 2%).", "takeaway_ko": "1차 백금·플루오로피리미딘 항암화학요법 중 또는 종료 후 4개월 이내에 진행한 진행성 위암 또는 위식도접합부 선암 환자에서, 파클리탁셀에 라무시루맙을 추가하자 위약+파클리탁셀 대비 전체생존기간이 개선되었습니다(중앙값 9.6개월 대 7.4개월, 위험비 0.807). 대신 3등급 이상 이상반응이 더 많았으며, 특히 호중구감소증(41% 대 19%), 백혈구감소증(17% 대 7%), 고혈압(14% 대 2%), 피로(12% 대 5%)가 증가했고, 3등급 이상 발열성 호중구감소증은 두 군 모두 낮았습니다(3% 대 2%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-REGARD", "trial": "G-REGARD", "papers": [ { "key": "P-REGARD", "pmid": "24094768", "title": "Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.", "journal": "Lancet", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24094768/", "doi": "10.1016/S0140-6736(13)61719-5", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "", "label": "REGARD", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Second line", "population": "Previously treated advanced gastric or GEJ adenocarcinoma", "claim": "Ramucirumab monotherapy vs placebo: OS 5.2 vs 3.8 months (HR 0.776).", "trialRecord": { "key": "G-REGARD", "nct": "NCT00917384", "acronym": null, "title": "Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 355, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2009-08", "lastUpdate": "2019-09-25", "url": "https://clinicaltrials.gov/study/NCT00917384" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 355, "assessment": "not stated", "quote": "We did an international, randomised, double-blind, placebo-controlled, phase 3 trial … 355 patients were assigned to receive ramucirumab (n=238) or placebo (n=117)." }, "effect": { "measure": "HR", "value": 0.776, "ci_low": 0.603, "ci_high": 0.998, "ci_level": "95%", "p": "0.047", "endpoint": "Overall survival", "quote": "Median overall survival was 5·2 months (IQR 2·3-9·9) in patients in the ramucirumab group and 3·8 months (1·7-7·1) in those in the placebo group (hazard ratio [HR] 0·776, 95% CI 0·603-0·998; p=0·047)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Five (2%) in the ramucirumab group and two (2%) in the placebo group", "quote": "Rates of hypertension were higher in the ramucirumab group than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered to be related to study drug." }, "takeaway_en": "In patients with advanced gastric or gastro-oesophageal junction adenocarcinoma that progressed after first-line platinum- or fluoropyrimidine-containing chemotherapy, ramucirumab 8 mg/kg every 2 weeks plus best supportive care improved median overall survival compared with placebo plus best supportive care (5.2 vs 3.8 months; HR 0.776, 95% CI 0.603-0.998). Hypertension was more common with ramucirumab (16% vs 8%), other adverse event rates were mostly similar, and study-drug-related deaths occurred in 2% of each arm.", "takeaway_ko": "1차 백금 또는 플루오로피리미딘 기반 항암화학요법 후 진행한 진행성 위암 또는 위식도접합부 선암 환자에서, 최선의 지지요법에 라무시루맙 8 mg/kg을 2주마다 추가한 경우 위약 대비 전체생존기간 중앙값이 개선되었습니다(5.2개월 대 3.8개월; 위험비 0.776, 95% 신뢰구간 0.603-0.998). 고혈압은 라무시루맙군에서 더 흔했고(16% 대 8%) 그 외 이상반응 발생률은 대체로 비슷했으며, 연구약물 관련 사망은 양군 모두 2%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RAINFALL", "trial": "G-RAINFALL", "papers": [ { "key": "P-RAINFALL", "pmid": "30718072", "title": "Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30718072/", "doi": "10.1016/S1470-2045(18)30791-5", "errata": [ { "pmid": "31044719", "title": "Correction to Lancet Oncol 2019; 20: 420-35.", "url": "https://pubmed.ncbi.nlm.nih.gov/31044719/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "The primary PFS analysis used the first 508 of 645 randomized patients. A sensitivity analysis with central independent imaging review did not corroborate the investigator-assessed PFS difference (HR 0.961, 95% CI 0.768-1.203; P = .74). The PFS findings were not consistent across assessors, while the nonsignificant secondary OS result does not establish equivalence. The trial enrolled HER2-negative disease with ECOG performance status 0-1. The linked correction concerns an adverse-event table percentage, which is not used in this efficacy claim.", "label": "RAINFALL", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First line", "population": "Metastatic gastric or GEJ adenocarcinoma", "claim": "Ramucirumab with cisplatin and fluoropyrimidine improved investigator-assessed PFS, the primary endpoint (5.7 vs 5.4 months; HR 0.753), but did not demonstrate a statistically significant improvement in overall survival, a secondary endpoint (HR 0.962, p = 0.6757).", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-RAINFALL", "nct": "NCT02314117", "acronym": "RAINFALL", "title": "A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 645, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-01-20", "lastUpdate": "2021-08-26", "url": "https://clinicaltrials.gov/study/NCT02314117" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 645, "assessment": "investigator", "quote": "For this double-blind, randomised, placebo-controlled, phase 3 trial done at 126 centres in 20 countries … The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients … 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidine and cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319)." }, "effect": { "measure": "HR", "value": 0.753, "ci_low": 0.607, "ci_high": 0.935, "ci_level": "95%", "p": "0.0106", "endpoint": "Investigator-assessed progression-free survival", "quote": "Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607-0·935, p=0·0106; median progression-free survival 5·7 months [5·5-6·5] vs 5·4 months [4·5-5·7])." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Seven in each group (ramucirumab: acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, sudden death; placebo: cerebrovascular accident, multiple organ dysfunction syndrome x2, pulmonary embolism x2, sepsis, small intestine perforation)", "quote": "The most common grade 3-4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group … There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events." }, "takeaway_en": "In 645 patients with metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, adding ramucirumab to first-line cisplatin plus fluoropyrimidine improved investigator-assessed progression-free survival (HR 0.753; median 5.7 vs 5.4 months), but this was not confirmed by central independent review (HR 0.961), and overall survival did not differ (HR 0.962; median 11.2 vs 10.7 months). Grade 3-4 hypertension was more frequent with ramucirumab (10% vs 2%), serious adverse events were similar (50% vs 47%), and there were seven treatment-related deaths in each group.", "takeaway_ko": "HER2 음성 전이성 위암 또는 위식도접합부 선암 환자 645명에서 1차 시스플라틴과 플루오로피리미딘 병용에 라무시루맙을 추가하자 연구자 평가 무진행생존이 개선되었습니다(HR 0.753, 중앙값 5.7개월 대 5.4개월). 그러나 독립 중앙 판독에서는 이 결과가 확인되지 않았고(HR 0.961), 전체생존에도 차이가 없었습니다(HR 0.962, 중앙값 11.2개월 대 10.7개월). 3-4등급 고혈압은 라무시루맙군에서 더 흔했으며(10% 대 2%), 중대한 이상반응 발생률은 비슷했고(50% 대 47%), 치료 관련 사망은 양군 모두 7명이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CLASSIC", "trial": "G-CLASSIC", "papers": [ { "key": "P-CLASSIC", "pmid": "22226517", "title": "Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.", "journal": "Lancet", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22226517/", "doi": "10.1016/S0140-6736(11)61873-4", "errata": [] }, { "key": "P-CLASSIC5y", "pmid": "25439693", "title": "Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial.", "journal": "Lancet Oncol", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25439693/", "doi": "10.1016/S1470-2045(14)70473-5", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The trial was open label, with observation rather than another active adjuvant regimen as comparator; it does not establish superiority over contemporary perioperative strategies. The primary report recorded grade 3 or 4 adverse events in 56% vs 6%, with nausea, neutropenia and decreased appetite common during chemotherapy. Adverse-event data were not collected after the primary analysis, limiting long-term safety inference. The primary and follow-up papers report the same trial.", "label": "CLASSIC", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant capecitabine plus oxaliplatin versus observation after curative D2 gastrectomy", "population": "Stage II-IIIB gastric cancer after curative D2 resection; trial conducted in South Korea, China and Taiwan", "claim": "At the preplanned final follow-up, 5-year DFS was 68% vs 53% (HR 0·58, 95% CI 0·47-0·72), and 5-year OS was 78% vs 69% (HR 0·66, 95% CI 0·51-0·85). Median follow-up was 62·4 months.", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-CLASSIC", "nct": "NCT00411229", "acronym": "CLASSIC", "title": "Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1035, "sponsor": "Sanofi", "sponsorClass": "INDUSTRY", "collaborators": [ "Hoffmann-La Roche" ], "hasResults": false, "start": "2006-06", "lastUpdate": "2013-02-20", "url": "https://clinicaltrials.gov/study/NCT00411229" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "3-year disease-free survival (intention to treat)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 1035, "assessment": "investigator", "quote": "The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial … Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked … 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only)." }, "effect": { "measure": "HR", "value": 0.58, "ci_low": 0.47, "ci_high": 0.72, "ci_level": "95%", "p": "p<0·0001", "endpoint": "Disease-free survival (final preplanned 5-year analysis, median follow-up 62·4 months)", "quote": "139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001)." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "5 years", "experimental_pct": 68, "control_pct": 53, "higher_is_better": true, "experimental_arm": "Adjuvant capecitabine plus oxaliplatin", "control_arm": "Observation", "quote": "Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group.", "difference_pp": 15, "nnt": 7, "quote_note": "From the most recent paper (P-CLASSIC5y, 5-year follow-up, median 62·4 months" }, { "endpoint": "Overall survival", "timepoint": "5 years", "experimental_pct": 78, "control_pct": 69, "higher_is_better": true, "experimental_arm": "Adjuvant capecitabine plus oxaliplatin", "control_arm": "Observation", "quote": "Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group.", "difference_pp": 9, "nnt": 12, "quote_note": "From the most recent paper (P-CLASSIC5y, 5-year follow-up, median 62·4 months" } ], "harms": { "grade3plus_experimental_pct": 56, "grade3plus_control_pct": 6, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294).", "quote_note": "From the 2012 interim paper (P-CLASSIC); the 5-year paper states adverse event data were not collected after the primary analysis" }, "takeaway_en": "In patients with stage II-IIIB gastric cancer after curative D2 gastrectomy in South Korea, China and Taiwan, 6 months of adjuvant capecitabine plus oxaliplatin was compared with observation. At 5 years, disease-free survival was 68% vs 53% and overall survival 78% vs 69%; the trade-off was grade 3 or 4 adverse events in 56% vs 6% of patients, mainly nausea, neutropenia and decreased appetite.", "takeaway_ko": "한국·중국·대만에서 근치적 D2 위절제술을 받은 II-IIIB기 위암 환자를 대상으로, 6개월간의 보조 카페시타빈·옥살리플라틴 요법과 경과관찰을 비교했습니다. 5년 무병생존율은 68% 대 53%, 5년 전체생존율은 78% 대 69%였습니다. 반면 3-4등급 이상반응은 56% 대 6%로 발생했으며, 주로 오심, 호중구감소증, 식욕감소였습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-JAVG100", "trial": "G-JAVG100", "papers": [ { "key": "P-JAVG100", "pmid": "33197226", "title": "Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33197226/", "doi": "10.1200/JCO.20.00892", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [], "subtypes": [ "G-HER2NEG" ], "limits": "Randomization followed induction and therefore selected patients without early progression. The trial was open label. An exploratory CPS-based subgroup used a different assay/scoring definition from the prespecified tumour-cell PD-L1 subgroup and does not reverse the negative primary result. Grade >=3 treatment-related adverse events occurred in 12.8% vs 32.8%. Lower observed toxicity does not establish survival superiority.", "label": "JAVELIN Gastric 100", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Avelumab switch maintenance versus continued chemotherapy after first-line induction", "population": "HER2-negative, unresectable locally advanced or metastatic gastric or GEJ cancer without progression after induction chemotherapy", "claim": "Among 499 randomized patients, median OS after induction was 10.4 months with avelumab vs 10.9 months with continued chemotherapy (HR 0.91, 95% CI 0.74-1.11; P=.1779). OS superiority was not demonstrated in either the overall population or the prespecified PD-L1-positive population.", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-JAVG100", "nct": "NCT02625610", "acronym": null, "title": "Avelumab in First-Line Maintenance Gastric Cancer (JAVELIN Gastric 100)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 499, "sponsor": "EMD Serono Research & Development Institute, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Merck KGaA, Darmstadt, Germany" ], "hasResults": true, "start": "2015-12-24", "lastUpdate": "2022-06-09", "url": "https://clinicaltrials.gov/study/NCT02625610" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 499, "assessment": "not stated", "quote": "JAVELIN Gastric 100 was a global, open-label, phase III trial. … A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250)." }, "effect": { "measure": "HR", "value": 0.91, "ci_low": 0.74, "ci_high": 1.11, "ci_level": "95%", "p": ".1779", "endpoint": "Overall survival after induction chemotherapy, all randomly assigned patients", "quote": "Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .1779)." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "24 months", "experimental_pct": 22.1, "control_pct": 15.5, "higher_is_better": true, "experimental_arm": "Avelumab maintenance", "control_arm": "Continued chemotherapy", "quote": "24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively", "difference_pp": 6.6, "nnt": 16, "quote_note": "single paper, J Clin Oncol 2021" } ], "harms": { "grade3plus_experimental_pct": 12.8, "grade3plus_control_pct": 32.8, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively.", "quote_note": "Grade ≥ 3 figures are treatment-related adverse events." }, "takeaway_en": "In patients with HER2-negative advanced gastric or GEJ cancer without progression after 12 weeks of oxaliplatin-fluoropyrimidine induction, switching to avelumab maintenance did not significantly improve overall survival versus continuing chemotherapy (median 10.4 vs 10.9 months; 24-month OS 22.1% vs 15.5%; HR 0.91, 95% CI 0.74-1.11). Grade ≥3 treatment-related adverse events were less frequent with avelumab (12.8%) than with continued chemotherapy (32.8%).", "takeaway_ko": "옥살리플라틴-플루오로피리미딘 유도 항암화학요법 12주 후 진행이 없었던 HER2 음성 진행성 위암 또는 위식도접합부암 환자에서, 아벨루맙 유지요법으로 전환한 군은 항암화학요법을 지속한 군에 비해 전체생존기간을 유의하게 개선하지 못했습니다(중앙값 10.4개월 대 10.9개월, 24개월 전체생존율 22.1% 대 15.5%, 위험비 0.91, 95% 신뢰구간 0.74-1.11). 3등급 이상 치료 관련 이상반응은 아벨루맙군(12.8%)이 항암화학요법 지속군(32.8%)보다 적었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DPT02", "trial": "X-DPT02", "papers": [ { "key": "P-DPT02", "pmid": "37870536", "title": "Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37870536/", "doi": "10.1200/JCO.23.02005", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "Cohort-level results for gynaecological cancers are not yet extracted.", "label": "DESTINY-PanTumor02", "program": "expansion", "kind": "single-arm", "level": "clinical", "result": "positive", "population": "HER2-expressing solid tumours in seven cohorts (endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, other)", "claim": "Trastuzumab deruxtecan: objective response 37.1% overall; in central HER2 IHC 3+ (n=75) 61.3%, median PFS 11.9 months, median OS 21.1 months.", "trialRecord": { "key": "X-DPT02", "nct": "NCT04482309", "acronym": "DPT02", "title": "A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 477, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo Co., Ltd." ], "hasResults": false, "start": "2020-08-18", "lastUpdate": "2026-07-10", "url": "https://clinicaltrials.gov/study/NCT04482309" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CLEOPATRA", "trial": "B-CLEOPATRA", "papers": [ { "key": "P-CLEOPATRA12", "pmid": "22149875", "title": "Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.", "journal": "N Engl J Med", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22149875/", "doi": "10.1056/NEJMoa1113216", "errata": [] }, { "key": "P-CLEOPATRA", "pmid": "32171426", "title": "Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study.", "journal": "Lancet Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32171426/", "doi": "10.1016/S1470-2045(19)30863-0", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "", "label": "CLEOPATRA", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, metastatic", "population": "HER2-positive metastatic breast cancer", "claim": "Pertuzumab plus trastuzumab and docetaxel: end-of-study median OS 57.1 vs 40.8 months (HR 0.69).", "trialRecord": { "key": "B-CLEOPATRA", "nct": "NCT00567190", "acronym": "CLEOPATRA", "title": "A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 808, "sponsor": "Genentech, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Hoffmann-La Roche" ], "hasResults": true, "start": "2008-02-12", "lastUpdate": "2019-12-13", "url": "https://clinicaltrials.gov/study/NCT00567190" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Independently assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 808, "assessment": "blinded independent central review", "quote": "This was a double-blind, randomised, placebo-controlled, phase 3 trial that was done at 204 centres in 25 countries. … The primary endpoint was independent review facility-assessed progression-free survival … 808 were enrolled and randomly assigned." }, "effect": { "measure": "HR", "value": 0.62, "ci_low": 0.51, "ci_high": 0.75, "ci_level": "95%", "p": "P<0.001", "endpoint": "Independently assessed progression-free survival (primary analysis, 2012)", "quote": "The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001)." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "8 years", "experimental_pct": 37, "control_pct": 23, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + docetaxel", "control_arm": "Placebo + trastuzumab + docetaxel", "quote": "8-year landmark overall survival rates were 37% (95% CI 31-42) in the pertuzumab group and 23% (19-28) in the placebo group.", "difference_pp": 14, "nnt": 8, "quote_note": "End-of-study analysis (Lancet Oncol 2020, median follow-up 99·9 vs 98·7 months; descriptive, not adjusted for crossover" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Five (1%) of 408 patients in the pertuzumab group and six (2%) of 396 patients in the placebo group", "quote": "The most common grade 3-4 adverse event was neutropenia (200 [49%] of 408 patients in the pertuzumab group, 183 [46%] of 396 patients in the placebo group). Five (1%) of 408 patients in the pertuzumab group and six (2%) of 396 patients in the placebo group had treatment-related deaths. … the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group." }, "takeaway_en": "In 808 patients with previously untreated HER2-positive metastatic breast cancer, adding pertuzumab to trastuzumab plus docetaxel improved the primary endpoint of progression-free survival (HR 0.62). At the end-of-study analysis, 8-year overall survival was 37% versus 23%. Grade 3 or higher febrile neutropenia and diarrhea were more frequent with pertuzumab, but left ventricular systolic dysfunction did not increase, and treatment-related deaths were 1% versus 2%.", "takeaway_ko": "이전 치료를 받지 않은 HER2 양성 전이성 유방암 환자 808명에서 트라스투주맙과 도세탁셀에 퍼투주맙을 추가하자 일차 평가변수인 무진행생존이 개선되었습니다(위험비 0.62). 연구 종료 분석에서 8년 전체생존율은 37% 대 23%였습니다. 퍼투주맙군에서 3등급 이상의 발열성 호중구감소증과 설사가 더 많았지만 좌심실 수축기능 장애는 증가하지 않았고, 치료 관련 사망은 1% 대 2%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-EMILIA", "trial": "B-EMILIA", "papers": [ { "key": "P-EMILIA", "pmid": "23020162", "title": "Trastuzumab emtansine for HER2-positive advanced breast cancer.", "journal": "N Engl J Med", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23020162/", "doi": "10.1056/NEJMoa1209124", "errata": [ { "pmid": null, "title": "N Engl J Med. 2013 Jun 20;368(25):2442", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx130019", "reviewed": true, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The publisher correction changes the aggregate adverse-event category from grades 3 or 4 to grade 3 or above in the abstract, safety text and table headings/footnote. The saved PubMed abstract retains the superseded wording, while the current publisher abstract uses the corrected category. The PFS values cited here are unchanged. Corrected tables and underlying patient data were not independently audited.", "label": "EMILIA", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Previously treated, advanced", "population": "HER2-positive advanced breast cancer", "claim": "Trastuzumab emtansine vs lapatinib plus capecitabine: PFS 9.6 vs 6.4 months (HR 0.65).", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-EMILIA", "nct": "NCT00829166", "acronym": "EMILIA", "title": "A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 991, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2009-02", "lastUpdate": "2016-10-31", "url": "https://clinicaltrials.gov/study/NCT00829166" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by independent review (co-primary with overall survival and safety)", "primary_endpoint_type": "PFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 991, "assessment": "not stated", "quote": "We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. … Among 991 randomly assigned patients" }, "effect": { "measure": "HR", "value": 0.65, "ci_low": 0.55, "ci_high": 0.77, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (independent review)", "quote": "median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001)" }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "not stated (best response, P-EMILIA 2012 report)", "experimental_pct": 43.6, "control_pct": 30.8, "higher_is_better": true, "experimental_arm": "Trastuzumab emtansine (T-DM1)", "control_arm": "Lapatinib plus capecitabine", "quote": "The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001)", "difference_pp": 12.8, "nnt": 8 } ], "harms": { "grade3plus_experimental_pct": 41, "grade3plus_control_pct": 57, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine." }, "takeaway_en": "In patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane, trastuzumab emtansine (T-DM1) was compared with lapatinib plus capecitabine. T-DM1 had a higher objective response rate (43.6% vs 30.8%), longer median independently reviewed progression-free survival (9.6 vs 6.4 months; HR 0.65), and longer median overall survival (30.9 vs 25.1 months; HR 0.68). Grade 3 or 4 adverse events were less frequent with T-DM1 (41% vs 57%). Thrombocytopenia and raised aminotransferases were more common with T-DM1, while diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were more common with lapatinib plus capecitabine.", "takeaway_ko": "트라스투주맙과 탁산 치료 경험이 있는 HER2 양성 진행성 유방암 환자에서 트라스투주맙 엠탄신(T-DM1)과 라파티닙+카페시타빈을 비교하였습니다. T-DM1군에서 객관적 반응률이 더 높았고(43.6% 대 30.8%), 독립 평가 무진행생존기간 중앙값(9.6개월 대 6.4개월, 위험비 0.65)과 전체생존기간 중앙값(30.9개월 대 25.1개월, 위험비 0.68)도 더 길었습니다. 3–4등급 이상반응은 T-DM1군에서 더 적었습니다(41% 대 57%). 혈소판감소증과 혈청 아미노전이효소 상승은 T-DM1군에서, 설사, 구역, 구토, 손발바닥 홍반성 감각이상은 라파티닙+카페시타빈군에서 더 흔했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-EGF100151", "trial": "B-EGF100151", "papers": [ { "key": "P-EGF100151", "pmid": "17192538", "title": "Lapatinib plus capecitabine for HER2-positive advanced breast cancer.", "journal": "N Engl J Med", "year": "2006", "url": "https://pubmed.ncbi.nlm.nih.gov/17192538/", "doi": "10.1056/NEJMoa064320", "errata": [ { "pmid": null, "title": "N Engl J Med. 2007 Apr 5;356(14):1487", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070016", "reviewed": true, "unresolvedIdentifier": true } ] }, { "key": "P-EGF100151OS", "pmid": "20736298", "title": "Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial.", "journal": "Oncologist", "year": "2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20736298/", "doi": "10.1634/theoncologist.2009-0181", "errata": [] } ], "pages": [ { "key": "nci-breast-targeted", "title": "NCI — Targeted Therapy for Breast Cancer", "url": "https://www.cancer.gov/types/breast/treatment/targeted-therapy", "file": "data/sources/pages/nci-breast-targeted.txt" } ], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [ "B-HER2POS" ], "limits": "Enrollment stopped early and crossover reduced power and complicates OS interpretation. The crossover-adjusted analysis was exploratory and does not replace the unadjusted result. The initial abstract reported no increase in serious toxic effects or symptomatic cardiac events, not an absence of toxicity. The complete publisher correction was reviewed and supplies a missing grade 4 adverse-event table footnote; it does not amend the initial time-to-progression estimates cited here. Corrected tables and underlying patient data were not independently audited. This historical comparator does not rank current HER2-directed options.", "label": "Lapatinib + capecitabine (EGF100151)", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "population": "Women with HER2-positive locally advanced or metastatic breast cancer progressing after regimens including anthracycline, taxane and trastuzumab", "claim": "The planned interim analysis found longer independently reviewed time to progression: 8.4 vs 4.4 months (HR 0.49, 95% CI 0.34-0.71). The final OS analysis reported 75.0 vs 64.7 weeks (HR 0.87, 95% CI 0.71-1.08; P=.210), without a significant unadjusted survival difference.", "setting": "Lapatinib plus capecitabine versus capecitabine after prior HER2-directed therapy and chemotherapy", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-EGF100151", "nct": "NCT00078572", "acronym": null, "title": "Capecitabine (XELODA) With Or Without Lapatinib (GW572016) For Women With Refractory Advanced or Metastatic Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 408, "sponsor": "GlaxoSmithKline", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2004-03", "lastUpdate": "2010-12-13", "url": "https://clinicaltrials.gov/study/NCT00078572" }, "sources": 4, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Time to progression, based on an evaluation by independent reviewers under blinded conditions", "primary_endpoint_type": "other", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 399, "assessment": "blinded independent central review", "quote": "The primary end point was time to progression, based on an evaluation by independent reviewers under blinded conditions. … At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment." }, "effect": { "measure": "HR", "value": 0.49, "ci_low": 0.34, "ci_high": 0.71, "ci_level": "95%", "p": "<0.001", "endpoint": "Independently assessed time to progression (interim analysis)", "quote": "The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events." }, "takeaway_en": "In women with HER2-positive advanced breast cancer that had progressed after an anthracycline, a taxane and trastuzumab, adding lapatinib to capecitabine lengthened independently reviewed time to progression compared with capecitabine alone (median 8.4 vs 4.4 months; HR 0.49, 95% CI 0.34-0.71). This came without an increase in serious toxic effects or symptomatic cardiac events, but the final overall survival analysis, which was affected by early enrollment termination and crossover, showed no significant difference (75.0 vs 64.7 weeks; HR 0.87, 95% CI 0.71-1.08; p = .210).", "takeaway_ko": "안트라사이클린, 탁산, 트라스투주맙 치료 후 진행한 HER2 양성 진행성 유방암 여성에서 카페시타빈에 라파티닙을 추가하자 카페시타빈 단독 대비 독립 평가 무진행 기간(time to progression)이 연장되었습니다(중앙값 8.4개월 대 4.4개월; HR 0.49, 95% CI 0.34-0.71). 중대한 독성이나 증상성 심장 사건은 증가하지 않았습니다. 다만 조기 등록 중단과 교차투여의 영향을 받은 최종 전체생존 분석에서는 유의한 차이가 없었습니다(75.0주 대 64.7주; HR 0.87, 95% CI 0.71-1.08; p = .210).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB03", "trial": "B-DB03", "papers": [ { "key": "P-DB03", "pmid": "35320644", "title": "Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35320644/", "doi": "10.1056/NEJMoa2115022", "errata": [] }, { "key": "P-DB03Long", "pmid": "38825627", "title": "Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial.", "journal": "Nat Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38825627/", "doi": "10.1038/s41591-024-03021-7", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "PFS differs by assessor (investigator vs BICR) and cutoff. Absence of new grade >=3 ILD does not mean never severe. No extrapolation to HER2-low/zero, gastric cancer, curative intent, or cross-trial superiority. Uses dated peer-reviewed 2024 follow-up rather than latest final results; 2026 conference final report was not fully verified for this record, and the full 2023 interim correction notice remains unread, so unique interim numbers are not adopted.", "label": "DESTINY-Breast03", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Second line, metastatic", "population": "HER2-positive metastatic breast cancer", "claim": "In DESTINY-Breast03 (524 randomized: 261 T-DXd vs 263 T-DM1) in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, primary 12-month BICR PFS was 75.8% vs 34.1% (HR 0.28). In this follow-up, at the 20 November 2023 cutoff, investigator-assessed median PFS was 29.0 vs 7.2 months (HR 0.30, 95% CI 0.24-0.38) and median OS was 52.6 vs 42.7 months (HR 0.73, 95% CI 0.56-0.94). All-grade ILD/pneumonitis was 16.7% vs 3.4%, with no new grade >=3 events.", "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8; reviewed by Muse Spark1.3; integrated by Codex (GPT-6)", "trialRecord": { "key": "B-DB03", "nct": "NCT03529110", "acronym": null, "title": "DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 524, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo Co., Ltd.", "AstraZeneca" ], "hasResults": true, "start": "2018-08-09", "lastUpdate": "2026-10-07", "url": "https://clinicaltrials.gov/study/NCT03529110" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as determined by blinded independent central review", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 524, "assessment": "blinded independent central review", "quote": "We conducted a phase 3, multicenter, open-label, randomized trial … The primary end point was progression-free survival (as determined by blinded independent central review) … Among 524 randomly assigned patients" }, "effect": { "measure": "HR", "value": 0.28, "ci_low": 0.22, "ci_high": 0.37, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression or death from any cause (PFS by blinded independent central review)", "quote": "hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001" }, "landmark": [ { "endpoint": "Progression-free survival (blinded independent central review)", "timepoint": "12 months", "experimental_pct": 75.8, "control_pct": 34.1, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan", "control_arm": "Trastuzumab emtansine", "quote": "the percentage of those who were alive without disease progression at 12 months was 75.8% (95% confidence interval [CI], 69.8 to 80.7) with trastuzumab deruxtecan and 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine", "difference_pp": 41.7, "nnt": 3, "quote_note": "primary analysis, N Engl J Med 2022; this time point is not updated in the later paper" }, { "endpoint": "Progression-free survival (investigator assessment)", "timepoint": "36 months", "experimental_pct": 45.7, "control_pct": 12.4, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan", "control_arm": "Trastuzumab emtansine", "quote": "the 36-month PFS rate was 45.7% versus 12.4%", "difference_pp": 33.3, "nnt": 4, "quote_note": "long-term analysis, Nat Med 2024, data cutoff 20 November 2023, median follow-up 41 months" }, { "endpoint": "Overall survival", "timepoint": "12 months", "experimental_pct": 94.1, "control_pct": 85.9, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan", "control_arm": "Trastuzumab emtansine", "quote": "The percentage of patients who were alive at 12 months was 94.1% (95% CI, 90.3 to 96.4) with trastuzumab deruxtecan and 85.9% (95% CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached)", "difference_pp": 8.2, "nnt": 13, "quote_note": "primary analysis, N Engl J Med 2022" }, { "endpoint": "Overall response (complete or partial response)", "timepoint": "Best response (primary analysis)", "experimental_pct": 79.7, "control_pct": 34.2, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan", "control_arm": "Trastuzumab emtansine", "quote": "An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine", "difference_pp": 45.5, "nnt": 3, "quote_note": "primary analysis, N Engl J Med 2022; the 2024 paper does not report updated response figures" } ], "harms": { "grade3plus_experimental_pct": 45.1, "grade3plus_control_pct": 39.8, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Not reported overall; adjudicated drug-related interstitial lung disease or pneumonitis included no grade 4 or 5 events", "quote": "the incidence of drug-related adverse events of grade 3 or 4 was 45.1% and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5. … No new instances of grade ≥3 interstitial lung disease or pneumonitis occurred (all grade rate, 16.7% (T-DXd) versus 3.4% (T-DM1)).", "quote_note": "Note: these are drug-related grade 3 or 4 events, not all grade ≥3 events.; Long-term update" }, "takeaway_en": "In patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, trastuzumab deruxtecan was compared with trastuzumab emtansine. Progression-free survival at 12 months was 75.8% versus 34.1% (HR 0.28), and at 36 months was 45.7% versus 12.4%, with median overall survival 52.6 versus 42.7 months (HR 0.73). The trade-off is more interstitial lung disease or pneumonitis (all grades 16.7% versus 3.4% at long-term follow-up, with no grade 4 or 5 events in the primary analysis) and slightly more drug-related grade 3 or 4 adverse events (45.1% versus 39.8%).", "takeaway_ko": "트라스투주맙과 탁산 치료 후 HER2 양성 전이성 유방암 환자에서 트라스투주맙 데룩스테칸(T-DXd)을 트라스투주맙 엠탄신(T-DM1)과 비교했습니다. 12개월 무진행생존율은 75.8% 대 34.1%(위험비 0.28), 36개월 무진행생존율은 45.7% 대 12.4%였고, 전체생존기간 중앙값은 52.6개월 대 42.7개월(위험비 0.73)이었습니다. 대신 간질성 폐질환 또는 폐렴이 더 많았고(장기 추적 시 전체 등급 16.7% 대 3.4%, 1차 분석에서 4~5등급 사례 없음), 약물 관련 3~4등급 이상반응도 다소 많았습니다(45.1% 대 39.8%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB04", "trial": "B-DB04", "papers": [ { "key": "P-DB04", "pmid": "35665782", "title": "Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35665782/", "doi": "10.1056/NEJMoa2203690", "errata": [] }, { "key": "P-DB04OS", "pmid": "41062831", "title": "Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41062831/", "doi": "10.1038/s41591-025-03981-4", "errata": [] }, { "key": "P-DB04PRO", "pmid": "40349139", "title": "Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician's choice of chemotherapy in patients with HER2-low mBC.", "journal": "Oncologist", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40349139/", "doi": "10.1093/oncolo/oyaf048", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2LOW-B" ], "subtypes": [ "B-HRPOS" ], "limits": "Long-term and patient-reported data are from the same NCT03734029 randomized trial, not new trials. Hormone receptor-negative and ER IHC subgroup OS results were exploratory. Similar on-treatment global scores do not establish equivalence given different exposure and deterioration timing. Applies only to previously treated HER2-low metastatic breast cancer.", "label": "DESTINY-Breast04", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Previously treated, metastatic", "population": "HER2-low metastatic breast cancer (88.7% hormone receptor-positive)", "claim": "In the hormone receptor-positive cohort at the original follow-up, trastuzumab deruxtecan versus physician's choice: PFS 10.1 versus 5.4 months (HR 0.51); OS 23.9 versus 17.5 months (HR 0.64). With an extended median follow-up of 32.0 months, OS in the overall cohort was 22.9 versus 16.8 months (HR 0.69; 95% CI 0.55-0.86) and OS in the hormone receptor-positive cohort was 23.9 versus 17.6 months (HR 0.69; 95% CI 0.55-0.87). Exploratory OS analyses in the hormone receptor-negative, ER IHC 1%-10% and ER IHC >10% subgroups also favored trastuzumab deruxtecan. In patient-reported outcomes for the hormone receptor-positive cohort, baseline global health status/quality of life was similar, with no clinically meaningful change during treatment despite longer exposure (8.2 versus 3.5 months). Median time to definitive deterioration in global health status/quality of life (11.4 versus 7.5 months; HR 0.69) and in all prespecified outcomes, including pain, favored trastuzumab deruxtecan, whereas nausea/vomiting deteriorated earlier with trastuzumab deruxtecan. Safety was described as acceptable and generally manageable.", "updated": "2026-09-30", "updatedBy": "Muse Spark1.3", "trialRecord": { "key": "B-DB04", "nct": "NCT03734029", "acronym": null, "title": "Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 557, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo Co., Ltd.", "AstraZeneca" ], "hasResults": true, "start": "2018-12-27", "lastUpdate": "2026-09-28", "url": "https://clinicaltrials.gov/study/NCT03734029" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival in the hormone receptor-positive cohort", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 557, "assessment": "not stated", "quote": "We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. … Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. … Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease." }, "effect": { "measure": "HR", "value": 0.51, "ci_low": null, "ci_high": null, "ci_level": null, "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death), hormone receptor-positive cohort", "quote": "In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 52.6, "grade3plus_control_pct": 67.4, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Adjudicated drug-related interstitial lung disease or pneumonitis with trastuzumab deruxtecan: 0.8% had grade 5 events", "quote": "Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events." }, "takeaway_en": "In patients with HER2-low metastatic breast cancer after one or two prior chemotherapy lines, trastuzumab deruxtecan was compared with physician's choice of chemotherapy. In the hormone receptor-positive cohort it lengthened median progression-free survival from 5.4 to 10.1 months (HR 0.51) and, at extended follow-up, median overall survival from 17.6 to 23.9 months (HR 0.69); grade 3 or higher adverse events were less frequent (52.6% vs 67.4%), but drug-related interstitial lung disease or pneumonitis occurred in 12.1% of patients, with grade 5 events in 0.8%.", "takeaway_ko": "이전에 1~2차 항암화학요법을 받은 HER2-low 전이성 유방암 환자에서 트라스투주맙 데룩스테칸을 의사 선택 항암화학요법과 비교하였습니다. 호르몬 수용체 양성 코호트에서 무진행 생존기간 중앙값이 5.4개월에서 10.1개월로 늘었고(위험비 0.51), 연장 추적 관찰에서 전체 생존기간 중앙값도 17.6개월에서 23.9개월로 늘었습니다(위험비 0.69). 3등급 이상 이상반응은 더 적었으나(52.6% 대 67.4%), 약물 관련 간질성 폐질환 또는 폐렴이 12.1%에서 발생했으며 0.8%는 5등급(사망) 사례였습니다.", "certainty": { "level": "moderate", "reasons": [ "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB06", "trial": "B-DB06", "papers": [ { "key": "P-DB06", "pmid": "39282896", "title": "Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39282896/", "doi": "10.1056/NEJMoa2407086", "errata": [] }, { "key": "P-DB06PRO", "pmid": "40441802", "title": "Patient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: results from the randomized DESTINY-Breast06 trial.", "journal": "ESMO Open", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40441802/", "doi": "10.1016/j.esmoop.2025.105082", "errata": [] }, { "key": "P-DB06Burden", "pmid": "41780642", "title": "Trastuzumab deruxtecan in hormone receptor-positive, HER2-low/-ultralow metastatic breast cancer (DESTINY-Breast06): outcome analyses by time to progression on prior first-line endocrine therapy with CDK4/6 inhibitor and baseline burden of disease.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41780642/", "doi": "10.1016/j.annonc.2026.02.015", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2LOW-B" ], "subtypes": [ "B-HRPOS" ], "limits": "Similar mean change-from-baseline global health status and quality-of-life scores between arms indicate preserved quality of life in patient-reported outcome analyses, not therapeutic equivalence. Subgroup analyses by prior endocrine therapy duration and baseline disease burden are exploratory post hoc evaluations from the intent-to-treat population and must not be conflated with the primary HER2-low endpoint. These two follow-up reports do not report overall survival results; no overall survival conclusion is drawn and progression endpoints are not combined with survival. Safety is consistent with known profiles without asserting complete absence of risk, noting increased gastrointestinal symptoms with trastuzumab deruxtecan. This synthesis provides clinical trial evidence and does not constitute patient treatment advice.", "label": "DESTINY-Breast06", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After endocrine therapy, chemotherapy-naive for metastatic disease", "population": "HR-positive, HER2-low (IHC 1+ or 2+/ISH−) or HER2-ultralow (IHC 0 with membrane staining)", "claim": "In the primary HER2-low population, median progression-free survival (PFS) was 13.2 versus 8.1 months (HR 0.62) with trastuzumab deruxtecan versus chemotherapy. In exploratory post hoc analyses, PFS and time to second progression or death (PFS2) favored trastuzumab deruxtecan regardless of time to progression on prior first-line endocrine therapy with a CDK4/6 inhibitor (<6, 6-12, or >12 months) and across disease-burden strata. Compared with chemotherapy, patient-reported outcomes indicated delayed deterioration in physical, role, and emotional functioning, fatigue, and pain, as well as fewer skin and mucosal symptoms. However, trastuzumab deruxtecan increased the risk of deterioration in, and the burden of, gastrointestinal symptoms, specifically nausea, vomiting, appetite loss, and constipation.", "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8", "trialRecord": { "key": "B-DB06", "nct": "NCT04494425", "acronym": "DB-06", "title": "Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 866, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo" ], "hasResults": true, "start": "2020-07-24", "lastUpdate": "2026-03-04", "url": "https://clinicaltrials.gov/study/NCT04494425" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival by blinded independent central review in patients with HER2-low disease", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 866, "assessment": "blinded independent central review", "quote": "We conducted a phase 3, multicenter, open-label trial … Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. … Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease." }, "effect": { "measure": "HR", "value": 0.62, "ci_low": 0.52, "ci_high": 0.75, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death), HER2-low population", "quote": "Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75; P<0.001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 52.8, "grade3plus_control_pct": 44.4, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Interstitial lung disease or pneumonitis: three grade 5 events in the trastuzumab deruxtecan group", "quote": "Adverse events of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan group and in 44.4% of those in the chemotherapy group. Adjudicated interstitial lung disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in severity) and in 1 patient (0.2%; grade 2), respectively." }, "takeaway_en": "In patients with HR-positive, HER2-low metastatic breast cancer who had received endocrine therapy but no chemotherapy for metastatic disease, trastuzumab deruxtecan was compared with physician's-choice chemotherapy and lengthened median progression-free survival from 8.1 to 13.2 months (HR 0.62); results were consistent in the exploratory HER2-ultralow population, and overall survival data were immature. Grade 3 or higher adverse events were more frequent with trastuzumab deruxtecan (52.8% vs 44.4%), and interstitial lung disease or pneumonitis occurred in 11.3% versus 0.2%, including three grade 5 events; patients also reported more nausea and vomiting, appetite loss, and constipation, but less pain and delayed functional decline.", "takeaway_ko": "내분비요법 후 전이성 질환에 대한 항암화학요법을 받지 않은 HR 양성, HER2-low 전이성 유방암 환자에서 트라스투주맙 데룩스테칸을 의사 선택 항암화학요법과 비교한 결과, 무진행생존기간 중앙값이 8.1개월에서 13.2개월로 연장되었습니다(위험비 0.62). 탐색적 HER2-ultralow 집단에서도 결과가 일관되었으며, 전체생존 자료는 아직 미성숙합니다. 3등급 이상 이상반응은 트라스투주맙 데룩스테칸군에서 더 많았고(52.8% 대 44.4%), 간질성 폐질환 또는 폐렴은 11.3% 대 0.2%로 발생했으며 이 중 5등급 사례가 3건 있었습니다. 환자 보고 결과에서는 오심·구토, 식욕 저하, 변비가 더 많았으나 통증은 적었고 기능 저하는 지연되었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB09", "trial": "B-DB09", "papers": [ { "key": "P-DB09", "pmid": "41160818", "title": "Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41160818/", "doi": "10.1056/NEJMoa2508668", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "", "label": "DESTINY-Breast09", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, metastatic", "population": "HER2-positive metastatic breast cancer", "claim": "Trastuzumab deruxtecan plus pertuzumab vs taxane, trastuzumab and pertuzumab (THP): median PFS 40.7 vs 26.9 months (HR 0.56).", "trialRecord": { "key": "B-DB09", "nct": "NCT04784715", "acronym": null, "title": "Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 1157, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo" ], "hasResults": false, "start": "2021-04-26", "lastUpdate": "2026-10-22", "url": "https://clinicaltrials.gov/study/NCT04784715" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by blinded independent central review", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "blinded independent central review", "quote": "We conducted a phase 3 trial involving patients with HER2-positive advanced or metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease. Patients were randomly assigned in a 1:1:1 ratio to receive trastuzumab deruxtecan plus pertuzumab; trastuzumab deruxtecan plus placebo; or a taxane, trastuzumab, and pertuzumab (THP). The primary end point was progression-free survival as assessed by blinded independent central review.", "quote_note": "Total randomized across all three arms not reported; this interim analysis reports 383 patients with trastuzumab deruxtecan plus pertuzumab and 387 with THP, and the trastuzumab deruxtecan plus placebo arm remains blinded." }, "effect": { "measure": "HR", "value": 0.56, "ci_low": 0.44, "ci_high": 0.71, "ci_level": "95%", "p": "P<0.00001 (P-value boundary for superiority, 0.00043)", "endpoint": "Progression-free survival (progression or death), interim analysis", "quote": "the median progression-free survival was 40.7 months with trastuzumab deruxtecan plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (hazard ratio for progression or death, 0.56; 95% confidence interval [CI], 0.44 to 0.71; P<0.00001 [P-value boundary for superiority, 0.00043])" }, "landmark": [ { "endpoint": "Confirmed objective response", "timepoint": "At data cutoff (February 26, 2025), prespecified interim analysis", "experimental_pct": 85.1, "control_pct": 78.6, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan plus pertuzumab", "control_arm": "Taxane, trastuzumab, and pertuzumab (THP)", "quote": "The incidence of a confirmed response was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP", "difference_pp": 6.5, "nnt": 16, "quote_note": "P-DB09, single paper, data cutoff February 26, 2025" }, { "endpoint": "Complete response", "timepoint": "At data cutoff (February 26, 2025), prespecified interim analysis", "experimental_pct": 15.1, "control_pct": 8.5, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan plus pertuzumab", "control_arm": "Taxane, trastuzumab, and pertuzumab (THP)", "quote": "(complete responses in 15.1% and 8.5%, respectively)", "difference_pp": 6.6, "nnt": 16, "quote_note": "P-DB09, single paper, data cutoff February 26, 2025" } ], "harms": { "grade3plus_experimental_pct": 63.5, "grade3plus_control_pct": 62.3, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Adjudicated drug-related interstitial lung disease or pneumonitis was grade 5 (death) in 2 patients receiving trastuzumab deruxtecan plus pertuzumab; none in the THP arm (all grade 1 or 2)", "quote": "The incidence of grade 3 or higher adverse events was 63.5% with trastuzumab deruxtecan plus pertuzumab and 62.3% with THP … Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.1% of patients receiving trastuzumab deruxtecan plus pertuzumab (grade 1 or 2 in 44 patients and grade 5 [death] in 2 patients) and in 1.0% of those receiving THP (all grade 1 or 2)." }, "takeaway_en": "In patients with previously untreated HER2-positive advanced or metastatic breast cancer, trastuzumab deruxtecan plus pertuzumab was compared with a taxane, trastuzumab and pertuzumab (THP) at a prespecified interim analysis. Median progression-free survival was 40.7 vs 26.9 months (HR 0.56), and confirmed response was 85.1% vs 78.6%. Grade 3 or higher adverse events were similar (63.5% vs 62.3%), but drug-related interstitial lung disease or pneumonitis occurred in 12.1% vs 1.0%, including 2 deaths in the trastuzumab deruxtecan arm.", "takeaway_ko": "이전에 치료받지 않은 HER2 양성 진행성 또는 전이성 유방암 환자를 대상으로 트라스투주맙 데룩스테칸+퍼투주맙과 탁산·트라스투주맙·퍼투주맙(THP) 병용요법을 비교한 사전 계획된 중간 분석입니다. 무진행생존기간 중앙값은 40.7개월 대 26.9개월(위험비 0.56)이었고, 확정 객관적 반응률은 85.1% 대 78.6%였습니다. 3등급 이상 이상반응은 63.5% 대 62.3%로 비슷했습니다. 그러나 약물 관련 간질성 폐질환 또는 폐렴은 12.1% 대 1.0%로 발생했으며, 트라스투주맙 데룩스테칸 군에서 2명이 사망했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-HER2CLIMB", "trial": "B-HER2CLIMB", "papers": [ { "key": "P-HER2CLIMB", "pmid": "31825569", "title": "Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.", "journal": "N Engl J Med", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31825569/", "doi": "10.1056/NEJMoa1914609", "errata": [ { "pmid": "31881136", "title": "Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/31881136/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "", "label": "HER2CLIMB", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Previously treated, metastatic", "population": "HER2-positive metastatic breast cancer", "claim": "Tucatinib added to trastuzumab and capecitabine: 1-year PFS 33.1% vs 12.3% (HR 0.54); median PFS 7.8 vs 5.6 months. Overall survival at 2 years was 44.9% vs 26.6% (HR 0.66, 95% CI 0.50 to 0.88; P = 0.005), and median overall survival was 21.9 vs 17.4 months.", "trialRecord": { "key": "B-HER2CLIMB", "nct": "NCT02614794", "acronym": "HER2CLIMB", "title": "A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 612, "sponsor": "Seagen Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2016-01-28", "lastUpdate": "2023-08-14", "url": "https://clinicaltrials.gov/study/NCT02614794" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival among the first 480 patients who underwent randomization", "primary_endpoint_type": "PFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 612, "assessment": "not stated", "quote": "We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients) …" }, "effect": { "measure": "HR", "value": 0.54, "ci_low": 0.42, "ci_high": 0.71, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively." }, "landmark": [ { "endpoint": "Progression-free survival", "timepoint": "1 year", "experimental_pct": 33.1, "control_pct": 12.3, "higher_is_better": true, "experimental_arm": "Tucatinib + trastuzumab + capecitabine", "control_arm": "Placebo + trastuzumab + capecitabine", "quote": "Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group", "difference_pp": 20.8, "nnt": 5, "quote_note": "only paper provided: N Engl J Med 2020, PMID 31825569" }, { "endpoint": "Overall survival", "timepoint": "2 years", "experimental_pct": 44.9, "control_pct": 26.6, "higher_is_better": true, "experimental_arm": "Tucatinib + trastuzumab + capecitabine", "control_arm": "Placebo + trastuzumab + capecitabine", "quote": "Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005)", "difference_pp": 18.3, "nnt": 6, "quote_note": "only paper provided: N Engl J Med 2020, PMID 31825569" }, { "endpoint": "Progression-free survival in patients with brain metastases", "timepoint": "1 year", "experimental_pct": 24.9, "control_pct": 0, "higher_is_better": true, "experimental_arm": "Tucatinib + trastuzumab + capecitabine", "control_arm": "Placebo + trastuzumab + capecitabine", "quote": "Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001)", "difference_pp": 24.9, "nnt": 5, "quote_note": "only paper provided: N Engl J Med 2020, PMID 31825569" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group." }, "takeaway_en": "In patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, with or without brain metastases, adding tucatinib rather than placebo to trastuzumab and capecitabine raised 1-year progression-free survival from 12.3% to 33.1% and 2-year overall survival from 26.6% to 44.9%. Grade 3 or higher diarrhea and elevated aminotransferase levels were more common with tucatinib; the abstract does not report their rates.", "takeaway_ko": "트라스투주맙, 퍼투주맙, 트라스투주맙 엠탄신으로 치료받은 적이 있는 HER2 양성 전이성 유방암 환자(뇌전이 유무 불문)에서 트라스투주맙과 카페시타빈에 위약 대신 투카티닙을 추가하자 1년 무진행생존율이 12.3%에서 33.1%로, 2년 전체생존율이 26.6%에서 44.9%로 높아졌습니다. 투카티닙군에서 3등급 이상의 설사와 아미노전이효소 상승이 더 흔했으나, 초록에는 그 발생률이 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ASCOCAP23", "trial": null, "papers": [ { "key": "P-ASCOCAP23", "pmid": "37284804", "title": "Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37284804/", "doi": "10.1200/JCO.22.02864", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HER2-B", "BM-HER2LOW-B" ], "subtypes": [], "limits": "", "label": "ASCO–CAP HER2 testing update 2023", "program": "breast", "kind": "guideline", "level": "literature", "result": "descriptive", "population": "Breast cancer", "claim": "ASCO–College of American Pathologists guideline update on HER2 testing in breast cancer (2023).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-monarchE", "trial": "B-monarchE", "papers": [ { "key": "P-monarchE", "pmid": "32954927", "title": "Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).", "journal": "J Clin Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32954927/", "doi": "10.1200/JCO.20.02514", "errata": [] }, { "key": "P-monarchE4y", "pmid": "36493792", "title": "Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial.", "journal": "Lancet Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36493792/", "doi": "10.1016/S1470-2045(22)00694-5", "errata": [] }, { "key": "P-monarchEOS", "pmid": "41110697", "title": "Overall survival with abemaciclib in early breast cancer.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41110697/", "doi": "10.1016/j.annonc.2025.10.005", "errata": [] }, { "key": "P-monarchENodes26", "pmid": "42815408", "title": "Abemaciclib plus endocrine therapy in HR-positive, HER2-negative high-risk early breast cancer: efficacy in nodal subgroups.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42815408/", "doi": "10.1016/j.esmoop.2026.108549", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "The earlier OS interim analysis had not shown a significant difference; the later prespecified OS result changes that maturity assessment without creating a second independent trial. This open-label study selected high-risk node-positive disease, not all HR-positive early breast cancers. The earlier safety report recorded grade 3-4 neutropenia in 19·6% vs 0·9% and diarrhoea in 7·8% vs 0·2%, with treatment-related deaths in the abemaciclib arm. The later report found no indication of delayed toxicity, which does not negate the earlier harms. The nodal report concerns cohort 1 high-risk eligibility. Its abstract supplies neither subgroup hazard ratios nor an interaction test, so similar patterns do not establish equal treatment effects across nodal categories. The nodal follow-up duration is distinct from the overall OS analysis above. Publisher full text was not accessible during this update; the new interpretation is abstract-bounded.", "label": "monarchE", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant abemaciclib plus endocrine therapy versus endocrine therapy alone", "population": "HR-positive, HER2-negative, node-positive early breast cancer selected for high recurrence risk", "claim": "At the later primary OS analysis, median follow-up was 76.2 months. OS HR was 0.842 (95% CI 0.722-0.981; P=0.027), meeting the prespecified significance boundary; 7-year OS was 86.8% vs 85.0%. Seven-year IDFS was 77.4% vs 70.9% (HR 0.734, 95% CI 0.657-0.820). A later cohort-specific report describes IDFS and distant recurrence-free survival patterns by nodal subgroup at a median follow-up of 76.8 months; it reports further follow-up of the same trial.", "updated": "2026-10-02", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-monarchE", "nct": "NCT03155997", "acronym": "monarchE", "title": "Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 5637, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [ "NSABP Foundation Inc" ], "hasResults": true, "start": "2017-07-12", "lastUpdate": "2026-04-24", "url": "https://clinicaltrials.gov/study/NCT03155997" }, "sources": 5, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (IDFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 5637, "assessment": "not stated", "quote": "In monarchE, an open-label, randomised, phase 3 trial … Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned" }, "effect": { "measure": "HR", "value": 0.734, "ci_low": 0.657, "ci_high": 0.82, "ci_level": "95%", "p": null, "endpoint": "IDFS (updated analysis, median follow-up 76.2 months)", "quote": "Sustained improvement was demonstrated in IDFS and DRFS (hazard ratio 0.734, 95% CI 0.657-0.820 and hazard ratio 0.746, 95% CI 0.662-0.840, respectively)." }, "landmark": [ { "endpoint": "IDFS", "timepoint": "7 years", "experimental_pct": 77.4, "control_pct": 70.9, "higher_is_better": true, "experimental_arm": "Abemaciclib + endocrine therapy", "control_arm": "Endocrine therapy alone", "quote": "Seven-year IDFS was 77.4% with abemaciclib-ET and 70.9% with ET (absolute difference, 6.5%)", "difference_pp": 6.5, "nnt": 16, "quote_note": "P-monarchEOS, Ann Oncol 2026, most recent; median follow-up 76.2 months" }, { "endpoint": "DRFS", "timepoint": "7 years", "experimental_pct": 80, "control_pct": 74.9, "higher_is_better": true, "experimental_arm": "Abemaciclib + endocrine therapy", "control_arm": "Endocrine therapy alone", "quote": "7-year DRFS were 80.0% and 74.9% (absolute difference, 5.1%)", "difference_pp": 5.1, "nnt": 20, "quote_note": "P-monarchEOS, Ann Oncol 2026, most recent" }, { "endpoint": "OS", "timepoint": "7 years", "experimental_pct": 86.8, "control_pct": 85, "higher_is_better": true, "experimental_arm": "Abemaciclib + endocrine therapy", "control_arm": "Endocrine therapy alone", "quote": "The 7-year OS was 86.8% with abemaciclib-ET and 85.0% with ET (absolute difference, 1.8%).", "difference_pp": 1.8, "nnt": 56, "quote_note": "P-monarchEOS, Ann Oncol 2026, most recent" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Two in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis); none in the endocrine therapy alone group", "quote": "The most common grade 3-4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group." }, "takeaway_en": "In HR-positive, HER2-negative, node-positive, high-risk early breast cancer, adding 2 years of adjuvant abemaciclib to endocrine therapy raised 7-year invasive disease-free survival from 70.9% to 77.4% (absolute difference, 6.5%) and 7-year overall survival from 85.0% to 86.8% (absolute difference, 1.8%). The trade-off is more toxicity. Grade 3-4 neutropenia occurred in 19.6% vs 0.9% of patients and grade 3-4 diarrhoea in 7.8% vs 0.2%, with two treatment-related deaths on abemaciclib.", "takeaway_ko": "호르몬 수용체 양성, HER2 음성, 림프절 양성 고위험 조기 유방암에서 보조 내분비요법에 아베마시클립 2년을 추가하자 7년 무침습질환생존율이 70.9%에서 77.4%로 높아졌습니다(절대 차이 6.5%). 7년 전체생존율도 85.0%에서 86.8%로 높아졌습니다(절대 차이 1.8%). 대신 독성이 증가하여 3-4등급 호중구감소증이 19.6% 대 0.9%, 3-4등급 설사가 7.8% 대 0.2%에서 발생했고, 아베마시클립군에서 치료 관련 사망이 2건 있었습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-NATALEE", "trial": "B-NATALEE", "papers": [ { "key": "P-NATALEE", "pmid": "38507751", "title": "Ribociclib plus Endocrine Therapy in Early Breast Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38507751/", "doi": "10.1056/NEJMoa2305488", "errata": [] }, { "key": "P-NATALEEfinal", "pmid": "39442617", "title": "A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial.", "journal": "Ann Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39442617/", "doi": "10.1016/j.annonc.2024.10.015", "errata": [] }, { "key": "P-NATALEE4y", "pmid": "40996773", "title": "Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial.", "journal": "JAMA Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40996773/", "doi": "10.1001/jamaoncol.2025.3700", "errata": [] }, { "key": "P-NATALEE5y", "pmid": "41320342", "title": "Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival.", "journal": "ESMO Open", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41320342/", "doi": "10.1016/j.esmoop.2025.105858", "errata": [] }, { "key": "P-NATALEE6y", "pmid": "42918423", "title": "Overall survival with adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with high-risk HR+/HER2- early breast cancer: Six-year follow-up of the NATALEE trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42918423/", "doi": "10.1016/j.annonc.2026.10.1288", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "Open-label trial in stage IIA (N1 or N0 with additional high-risk factors), IIB or III HR-positive/HER2-negative disease; findings do not cover all node-negative early cancers. Invasive disease-free survival includes invasive disease, recurrence or death and is not a recurrence-only or cure endpoint. The final planned iDFS, exploratory four-year and prespecified five-year analyses are reports of the same trial; their estimates and follow-up times are kept distinct. The received abstracts give no quantitative safety rates; no new safety signals does not mean no harm. The authors describe the six-year OS analysis as prespecified and descriptive, with a nominal P value; the OS difference is 2.1 percentage points.", "label": "NATALEE", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant", "population": "HR+, HER2− early breast cancer", "claim": "At the prespecified six-year analysis (median OS follow-up 66.5 months), ribociclib plus a nonsteroidal aromatase inhibitor versus the aromatase inhibitor alone showed an overall survival benefit: HR 0.809 (95% CI 0.661–0.989; nominal one-sided P=.019), a 2.1-percentage-point absolute OS difference at six years. The invasive disease-free survival benefit increased: HR 0.741 (95% CI 0.646–0.849), a 5.3-percentage-point difference at six years. At the earlier five-year follow-up, iDFS HR was 0.716 (95% CI 0.618–0.829) and OS was still maturing (HR 0.800, 95% CI 0.637–1.003).", "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "trialRecord": { "key": "B-NATALEE", "nct": "NCT03701334", "acronym": "NATALEE", "title": "A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 5101, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [ "Translational Research in Oncology" ], "hasResults": false, "start": "2018-12-07", "lastUpdate": "2026-10-09", "url": "https://clinicaltrials.gov/study/NCT03701334" }, "sources": 6, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (iDFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 5101, "assessment": "not stated", "quote": "In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio … Among 5101 patients included in the analysis" }, "effect": { "measure": "HR", "value": 0.741, "ci_low": 0.646, "ci_high": 0.849, "ci_level": "95%", "p": "nominal 1-sided P < .0001", "endpoint": "iDFS (6-year analysis, most recent)", "quote": "An increasing iDFS benefit with ribociclib plus NSAI was also observed (6-year ΔiDFS, 5.3%; HR, 0.741 [95% CI: 0.646-0.849]; nominal 1-sided P < .0001)" }, "landmark": [ { "endpoint": "iDFS", "timepoint": "3 years", "experimental_pct": 90.8, "control_pct": 88.1, "higher_is_better": true, "experimental_arm": "Ribociclib + NSAI", "control_arm": "NSAI alone", "quote": "with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points)", "difference_pp": 2.7, "nnt": 38, "quote_note": "P-NATALEE4y, most recent paper reporting both-arm 3-year rates; median iDFS follow-up 44.2 months" }, { "endpoint": "iDFS", "timepoint": "4 years", "experimental_pct": 88.5, "control_pct": 83.6, "higher_is_better": true, "experimental_arm": "Ribociclib + NSAI", "control_arm": "NSAI alone", "quote": "and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points)", "difference_pp": 4.9, "nnt": 21, "quote_note": "P-NATALEE4y, exploratory 4-year analysis; later papers report only between-arm differences" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "No new safety signals were observed. … The incidence of adverse events has remained stable." }, "takeaway_en": "In adults with HR-positive, HER2-negative stage II–III early breast cancer, this trial compared 3 years of adjuvant ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) with an NSAI alone. At 4 years, invasive disease-free survival was 88.5% versus 83.6%. At the 6-year analysis, the absolute differences were 5.3% for invasive disease-free survival and 2.1% for overall survival (HR 0.809; descriptive analysis with a nominal P value). The abstracts report no new safety signals but give no adverse-event or discontinuation rates, so the harm trade-off cannot be quantified from them.", "takeaway_ko": "HR 양성, HER2 음성 2–3기 조기 유방암 환자에서, 보조요법으로 리보시클립 3년과 비스테로이드성 아로마타제 억제제(NSAI) 병용을 NSAI 단독과 비교한 연구입니다. 4년 침습성 무질병 생존율(iDFS)은 88.5% 대 83.6%였습니다. 6년 분석에서 절대 차이는 iDFS 5.3%, 전체 생존율 2.1%였습니다(HR 0.809, 명목상 P값을 사용한 기술적 분석). 초록에서는 새로운 안전성 신호가 없었다고만 보고하며, 이상반응이나 투약 중단 비율은 제시하지 않아 위해 측면의 득실은 정량화할 수 없습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PALLAS", "trial": "B-PALLAS", "papers": [ { "key": "P-PALLAS", "pmid": "33460574", "title": "Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33460574/", "doi": "10.1016/S1470-2045(20)30642-2", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "PALLAS", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Adjuvant", "population": "Stage II–III HR+, HER2− early breast cancer", "claim": "Palbociclib plus endocrine therapy: 3-year IDFS 88.2% vs 88.5% (HR 0.93, p = 0.51) at the second interim analysis.", "trialRecord": { "key": "B-PALLAS", "nct": "NCT02513394", "acronym": "PALLAS", "title": "PALbociclib CoLlaborative Adjuvant Study", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 5796, "sponsor": "Alliance Foundation Trials, LLC.", "sponsorClass": "OTHER", "collaborators": [ "Austrian Breast & Colorectal Cancer Study Group", "NSABP Foundation Inc", "PrECOG, LLC.", "Breast International Group", "Pfizer" ], "hasResults": true, "start": "2015-08", "lastUpdate": "2026-06-15", "url": "https://clinicaltrials.gov/study/NCT02513394" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival in the intention-to-treat population", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 5760, "assessment": "not stated", "quote": "PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study … Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877)." }, "effect": { "measure": "HR", "value": 0.93, "ci_low": 0.76, "ci_high": 1.15, "ci_level": "95%", "p": "log-rank p=0·51", "endpoint": "Invasive disease-free survival", "quote": "hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51" }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "3 years", "experimental_pct": 88.2, "control_pct": 88.5, "higher_is_better": true, "experimental_arm": "Palbociclib plus endocrine therapy", "control_arm": "Endocrine therapy alone", "quote": "3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone", "difference_pp": -0.3, "nnt": null, "nnt_label": "favours control", "quote_note": "second pre-planned interim analysis, median follow-up of 23·7 months; only paper provided", "nnh": 334 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "There were no treatment-related deaths.", "quote": "The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths." }, "takeaway_en": "In 5760 patients with stage II–III HR-positive, HER2-negative early breast cancer, adding 2 years of palbociclib to adjuvant endocrine therapy gave 3-year invasive disease-free survival of 88.2% versus 88.5% with endocrine therapy alone at the second interim analysis (HR 0.93), so there was no meaningful difference, and the futility boundary was crossed. Palbociclib caused grade 3-4 neutropenia in 61.3% versus 0.3% of patients and serious adverse events in 12.4% versus 7.6%, with no treatment-related deaths.", "takeaway_ko": "2기–3기 호르몬수용체 양성, HER2 음성 조기 유방암 환자 5760명에서 보조 내분비요법에 팔보시클립 2년을 추가한 결과, 2차 중간분석 시점의 3년 침습적 무질병 생존율은 88.2%로 내분비요법 단독군의 88.5%와 의미 있는 차이가 없었습니다(위험비 0.93). 이에 따라 무익성 경계를 넘었습니다. 팔보시클립군에서 3-4등급 호중구감소증이 61.3%(대조군 0.3%), 중대한 이상반응이 12.4%(대조군 7.6%) 발생했으며, 치료 관련 사망은 없었습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PENELOPEB", "trial": "B-PENELOPEB", "papers": [ { "key": "P-PENELOPEB", "pmid": "33793299", "title": "Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33793299/", "doi": "10.1200/JCO.20.03639", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "PENELOPE-B", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Post-neoadjuvant", "population": "HR+, HER2− early breast cancer with residual invasive disease after neoadjuvant chemotherapy", "claim": "Palbociclib did not improve invasive disease-free survival (stratified HR 0.93; P = .525).", "trialRecord": { "key": "B-PENELOPEB", "nct": "NCT01864746", "acronym": "PENELOPE-B", "title": "A Study of Palbociclib in Addition to Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After Neoadjuvant Chemotherapy and Surgery", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1250, "sponsor": "GBG Forschungs GmbH", "sponsorClass": "OTHER", "collaborators": [ "Pfizer", "AGO Study Group", "NSABP Foundation Inc", "Breast International Group" ], "hasResults": true, "start": "2013-10-30", "lastUpdate": "2023-12-12", "url": "https://clinicaltrials.gov/study/NCT01864746" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (iDFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": null, "assessment": "not stated", "quote": "PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study … Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). … One thousand two hundred fifty patients were randomly assigned." }, "effect": { "measure": "HR", "value": 0.93, "ci_low": 0.74, "ci_high": 1.17, "ci_level": "95%", "p": ".525", "endpoint": "iDFS (stratified; 95% repeated CI; two-sided weighted log-rank test)", "quote": "After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P = .525." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Not reported as treatment-related; eight fatal serious adverse events in total (two palbociclib, six placebo), with attribution not stated.", "quote": "Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported." }, "takeaway_en": "In women with HR-positive, HER2-negative early breast cancer who had high-risk residual invasive disease after taxane-containing neoadjuvant chemotherapy, adding 1 year of palbociclib to endocrine therapy did not improve invasive disease-free survival compared with placebo (stratified HR 0.93, 95% repeated CI 0.74 to 1.17; P = .525) at a median follow-up of 42.8 months. The abstract does not report grade 3 or higher adverse events by arm; the most common related serious adverse events, infections and vascular disorders, occurred in 9.1% of patients with no difference between arms, and eight fatal serious adverse events were reported (two palbociclib, six placebo).", "takeaway_ko": "탁산 포함 선행항암화학요법 후 고위험 잔존 침습암이 있는 호르몬수용체 양성, HER2 음성 조기 유방암 여성에서 내분비요법에 팔보시클립 1년을 추가해도 위약 대비 침습적 무질병생존이 개선되지 않았습니다(중앙 추적관찰 42.8개월, 층화 위험비 0.93, 95% 반복 신뢰구간 0.74–1.17, P = .525). 초록에는 군별 3등급 이상 이상반응이 보고되지 않았습니다. 가장 흔한 관련 중대한 이상반응은 감염과 혈관 장애로 전체 환자의 9.1%에서 발생했으며 두 군 간 차이는 없었습니다. 치명적 중대한 이상반응은 8건(팔보시클립군 2건, 위약군 6건)이었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-SOLAR1", "trial": "B-SOLAR1", "papers": [ { "key": "P-SOLAR1", "pmid": "31091374", "title": "Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31091374/", "doi": "10.1056/NEJMoa1813904", "errata": [] } ], "pages": [], "targets": [ "PIK3CA" ], "biomarkers": [ "BM-PI3K" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "SOLAR-1", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After endocrine therapy, advanced", "population": "PIK3CA-mutated HR+, HER2− advanced breast cancer", "claim": "Alpelisib plus fulvestrant: PFS 11.0 vs 5.7 months in the PIK3CA-mutated cohort. Grade 3–4 hyperglycaemia 36.6% with alpelisib.", "trialRecord": { "key": "B-SOLAR1", "nct": "NCT02437318", "acronym": "SOLAR-1", "title": "Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 572, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-07-23", "lastUpdate": "2025-02-13", "url": "https://clinicaltrials.gov/study/NCT02437318" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival, as assessed by the investigator, in the cohort with PIK3CA-mutated cancer", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 572, "assessment": "investigator", "quote": "In a randomized, phase 3 trial, we compared alpelisib (at a dose of 300 mg per day) plus fulvestrant (at a dose of 500 mg every 28 days and once on day 15) with placebo plus fulvestrant … The primary end point was progression-free survival, as assessed by the investigator, in the cohort with PIK3CA-mutated cancer … A total of 572 patients underwent randomization, including 341 patients with confirmed tumor-tissue PIK3CA mutations." }, "effect": { "measure": "HR", "value": 0.65, "ci_low": 0.5, "ci_high": 0.85, "ci_level": "95%", "p": "<0.001", "endpoint": "Progression-free survival (progression or death), PIK3CA-mutated cohort", "quote": "In the cohort of patients with PIK3CA-mutated cancer, progression-free survival at a median follow-up of 20 months was 11.0 months (95% confidence interval [CI], 7.5 to 14.5) in the alpelisib-fulvestrant group, as compared with 5.7 months (95% CI, 3.7 to 7.4) in the placebo-fulvestrant group (hazard ratio for progression or death, 0.65; 95% CI, 0.50 to 0.85; P<0.001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 25, "discontinuation_control_pct": 4.2, "treatment_related_deaths": null, "quote": "In the overall population, the most frequent adverse events of grade 3 or 4 were hyperglycemia (36.6% in the alpelisib-fulvestrant group vs. 0.7% in the placebo-fulvestrant group) and rash (9.9% vs. 0.3%). Diarrhea of grade 3 occurred in 6.7% of patients in the alpelisib-fulvestrant group, as compared with 0.3% of those in the placebo-fulvestrant group; no diarrhea of grade 4 was reported. The percentages of patients who discontinued alpelisib and placebo owing to adverse events were 25.0% and 4.2%, respectively." }, "takeaway_en": "In patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer previously treated with endocrine therapy, alpelisib plus fulvestrant extended median progression-free survival compared with placebo plus fulvestrant (11.0 vs 5.7 months; hazard ratio 0.65). The trade-off was substantially more toxicity: grade 3 or 4 hyperglycemia occurred in 36.6% vs 0.7% and grade 3 or 4 rash in 9.9% vs 0.3%, and 25.0% vs 4.2% discontinued treatment because of adverse events.", "takeaway_ko": "내분비요법 치료력이 있는 PIK3CA 변이 HR 양성, HER2 음성 진행성 유방암 환자에서 알펠리십과 풀베스트란트 병용은 위약과 풀베스트란트 병용에 비해 무진행생존기간 중앙값을 연장했습니다(11.0개월 대 5.7개월, 위험비 0.65). 그 대가로 독성이 크게 증가했습니다. 3–4등급 고혈당은 36.6% 대 0.7%, 3–4등급 발진은 9.9% 대 0.3%에서 발생했으며, 이상반응으로 인한 투약 중단은 25.0% 대 4.2%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CAP291", "trial": "B-CAP291", "papers": [ { "key": "P-CAP291", "pmid": "37256976", "title": "Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37256976/", "doi": "10.1056/NEJMoa2214131", "errata": [] } ], "pages": [ { "key": "cap291-final-os-417o", "title": "CAPItello-291 — ESMO Breast 2026 congress abstract 417O: final OS", "url": "https://www.esmoopen.com/article/S2059-7029(26)01382-7/fulltext", "file": "data/sources/pages/cap291-final-os-417o.txt" } ], "targets": [ "AKT" ], "biomarkers": [ "BM-PI3K" ], "subtypes": [ "B-HRPOS" ], "limits": "The PFS-positive result and the final OS result concern different endpoints in the same trial. The final OS source is a congress abstract, not a full-length report; a nonsignificant result does not prove equivalence or exclude benefit. Secondary PFS2 and exploratory time to first subsequent chemotherapy or death do not substitute for OS. Aggregate population results do not establish efficacy separately for each alteration or the non-altered subgroup. In the 2023 primary report, grade ≥3 rash was 12.1% vs 0.3%, diarrhea 9.3% vs 0.3%, and adverse-event discontinuation 13.0% vs 2.3% with capivasertib versus placebo, both with fulvestrant. No new independent trial or RISCON patient analysis is added.", "label": "CAPItello-291", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "After endocrine therapy, advanced", "population": "HR+, HER2− advanced breast cancer (40.8% with AKT pathway alterations; 69.1% after a CDK4/6 inhibitor)", "claim": "Capivasertib plus fulvestrant improved PFS: 7.2 vs 3.6 months overall (HR 0.60), with benefit also in AKT pathway-altered tumors. In the final OS analysis, reported as a 2026 congress abstract, OS was not significantly improved: altered-population HR 0.83 (95% CI 0.63–1.10; p=0.201), overall HR 1.00 (95% CI 0.83–1.19; p=0.966).", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex source check and integration", "trialRecord": { "key": "B-CAP291", "nct": "NCT04305496", "acronym": "CAPItello-291", "title": "Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 818, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2020-04-16", "lastUpdate": "2026-04-30", "url": "https://clinicaltrials.gov/study/NCT04305496" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (dual primary end point: overall population and AKT pathway-altered [PIK3CA, AKT1, or PTEN] population)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 708, "assessment": "investigator", "quote": "In a phase 3, randomized, double-blind trial … The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors … Overall, 708 patients underwent randomization" }, "effect": { "measure": "HR", "value": 0.6, "ci_low": 0.51, "ci_high": 0.71, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival, overall population", "quote": "In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 13, "discontinuation_control_pct": 2.3, "treatment_related_deaths": null, "quote": "The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo." }, "takeaway_en": "In 708 patients with HR-positive, HER2-negative advanced breast cancer that relapsed or progressed during or after an aromatase inhibitor (69.1% after a prior CDK4/6 inhibitor), adding capivasertib to fulvestrant improved median progression-free survival from 3.6 to 7.2 months versus placebo plus fulvestrant (HR 0.60; 95% CI 0.51 to 0.71). The benefit was also seen in AKT pathway-altered tumors (7.3 vs 3.1 months; HR 0.50). The trade-off was more grade 3 or higher rash (12.1% vs 0.3%) and diarrhea (9.3% vs 0.3%), and more discontinuation for adverse events (13.0% vs 2.3%); overall survival is not reported in this abstract.", "takeaway_ko": "아로마타제 억제제 치료 중 또는 치료 후 재발하거나 진행한 호르몬 수용체 양성, HER2 음성 진행성 유방암 환자 708명(69.1%는 CDK4/6 억제제 치료 경험)을 대상으로 했습니다. 풀베스트란트에 카피바서팁을 추가하자 위약 병용군에 비해 무진행생존기간 중앙값이 3.6개월에서 7.2개월로 늘었습니다(위험비 0.60, 95% 신뢰구간 0.51–0.71). AKT 경로 변이 종양에서도 효과가 확인되었습니다(7.3개월 대 3.1개월, 위험비 0.50). 반면 3등급 이상 발진(12.1% 대 0.3%)과 설사(9.3% 대 0.3%), 이상반응으로 인한 투약 중단(13.0% 대 2.3%)이 더 많았으며, 전체생존기간은 이 초록에 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-INAVO120", "trial": "B-INAVO120", "papers": [ { "key": "P-INAVO120", "pmid": "39476340", "title": "Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39476340/", "doi": "10.1056/NEJMoa2404625", "errata": [] }, { "key": "P-INAVO120OS", "pmid": "40454641", "title": "Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454641/", "doi": "10.1056/NEJMoa2501796", "errata": [] }, { "key": "P-INAVO120Safety", "pmid": "42202490", "title": "Safety analyses of the INAVO120 randomised phase III trial of inavolisib or placebo with palbociclib-fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-resistant advanced breast cancer.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42202490/", "doi": "10.1016/j.esmoop.2026.107735", "errata": [] } ], "pages": [], "targets": [ "PIK3CA", "CDK4/6" ], "biomarkers": [ "BM-PI3K" ], "subtypes": [ "B-HRPOS" ], "limits": "Findings are restricted to first-line advanced PIK3CA-mutated, HR-positive, HER2-negative breast cancer relapsing during or within 12 months after completion of adjuvant endocrine therapy, and do not establish benefit across all CDK4/6 inhibitor-resistant or later-line cancers. The 2026 safety report reflects a data cutoff of September 29, 2023 rather than follow-up through 2026, and its selected safety analyses remain descriptive without establishing causal management efficacy. Furthermore, inavolisib interruption due to hyperglycemia occurred in 27.2% of patients, which differs markedly from inavolisib discontinuation due to hyperglycemia in 0.6%.", "label": "INAVO120", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, endocrine-resistant", "population": "PIK3CA-mutated HR+, HER2− advanced breast cancer", "claim": "In the initial report, in patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer that relapsed during or within 12 months after completing adjuvant endocrine therapy, first-line inavolisib plus palbociclib and fulvestrant significantly improved progression-free survival compared with placebo plus palbociclib and fulvestrant (median 15.0 vs 7.3 months; HR 0.43, 95% CI 0.32-0.59), with an objective response rate of 58.4% vs 25.0%. In the final overall survival analysis, median OS was significantly longer with inavolisib: 34.0 vs 27.0 months (HR 0.67, 95% CI 0.48-0.94; P = 0.02, crossing the prespecified significance boundary of P < 0.0469). In the OS report, adverse events led to discontinuation of inavolisib in 6.8% of patients versus discontinuation of placebo in 0.6%; hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxicities, and ocular harms were more frequent with inavolisib.", "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8; reviewed by Muse Spark1.3; integrated by Codex (GPT-6)", "trialRecord": { "key": "B-INAVO120", "nct": "NCT04191499", "acronym": "INAVO120", "title": "A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 325, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2020-01-29", "lastUpdate": "2026-09-11", "url": "https://clinicaltrials.gov/study/NCT04191499" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by the investigator", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": null, "assessment": "investigator", "quote": "In a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib-fulvestrant (inavolisib group) with placebo plus palbociclib-fulvestrant (placebo group) … The primary end point was progression-free survival as assessed by the investigator. … A total of 161 patients were assigned to the inavolisib group and 164 to the placebo group" }, "effect": { "measure": "HR", "value": 0.43, "ci_low": 0.32, "ci_high": 0.59, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (primary analysis, median follow-up 21.3 vs 21.5 months)", "quote": "The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001).", "quote_note": "P-INAVO120, primary analysis; the later OS report gives an updated hazard ratio for disease progression or death of 0.42 (95% CI, 0.32 to 0.55" }, "landmark": [ { "endpoint": "Objective response", "timepoint": "Final overall survival analysis (median follow-up 34.2 vs 32.3 months)", "experimental_pct": 62.7, "control_pct": 28, "higher_is_better": true, "experimental_arm": "Inavolisib plus palbociclib-fulvestrant", "control_arm": "Placebo plus palbociclib-fulvestrant", "quote": "An objective response occurred in 62.7% (95% CI, 54.8 to 70.2) of patients in the inavolisib group and 28.0% (95% CI, 21.3 to 35.6) of those in the placebo group (P<0.001).", "difference_pp": 34.7, "nnt": 3, "quote_note": "P-INAVO120OS, most recent report; the initial report gave 58.4% vs 25.0%" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 6.8, "discontinuation_control_pct": 0.6, "treatment_related_deaths": null, "quote": "Adverse events led to discontinuation of inavolisib in 6.8% of patients and discontinuation of placebo in 0.6%. The incidence of hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects (e.g., diarrhea), and ocular toxic effects (e.g., dry eye and blurred vision) was higher with inavolisib than with placebo." }, "takeaway_en": "In patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer that relapsed during or within 12 months after adjuvant endocrine therapy, adding inavolisib to first-line palbociclib-fulvestrant raised the objective response rate to 62.7% vs 28.0% with placebo, with progression-free survival HR 0.43 and median overall survival of 34.0 vs 27.0 months. The trade-off was more hyperglycemia (grade 3 or 4: 5.6% vs 0%), stomatitis or mucosal inflammation, diarrhea, and ocular toxic effects, and adverse events led to discontinuation of inavolisib in 6.8% vs 0.6% for placebo.", "takeaway_ko": "보조 내분비요법 중 또는 종료 후 12개월 이내에 재발한 PIK3CA 변이 호르몬수용체 양성, HER2 음성 진행성 유방암 환자에서 1차 팔보시클립-풀베스트란트에 이나볼리십을 추가하자 객관적 반응률이 62.7%로 위약군 28.0%보다 높았습니다. 무진행생존 위험비는 0.43이었고, 전체생존기간 중앙값은 34.0개월 대 27.0개월이었습니다. 대신 고혈당(3~4등급 5.6% 대 0%), 구내염 또는 점막염, 설사, 안구 독성이 더 많았으며, 이상반응으로 인한 투약 중단은 이나볼리십군 6.8%, 위약군 0.6%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RLY2608", "trial": "B-ReDiscover", "papers": [ { "key": "P-RLY2608", "pmid": "37916956", "title": "Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia.", "journal": "Cancer Discov", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37916956/", "doi": "10.1158/2159-8290.CD-23-0944", "errata": [] } ], "pages": [], "targets": [ "PIK3CA" ], "biomarkers": [ "BM-PI3K" ], "subtypes": [ "B-HRPOS" ], "limits": "Clinical results beyond proof of concept are not curated. A phase 3 (NCT06982521, started 2025-08) is listed on ClinicalTrials.gov.", "label": "RLY-2608", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "population": "PIK3CA-mutant models; first-in-human phase 1 (ReDiscover, recruiting)", "claim": "Molecular dynamics simulations and cryo-EM identified an allosteric network explaining mutant PI3Kα activation; RLY-2608 was reported as a first-in-class mutant-selective allosteric inhibitor. The paper states that orthosteric PI3Kα inhibitors cause hyperglycaemia by inhibiting wild-type PI3Kα.", "trialRecord": { "key": "B-ReDiscover", "nct": "NCT05216432", "acronym": null, "title": "First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer", "status": "RECRUITING", "phases": [ "PHASE1" ], "enrollment": 930, "sponsor": "Relay Therapeutics, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2021-12-08", "lastUpdate": "2025-09-22", "url": "https://clinicaltrials.gov/study/NCT05216432" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-EMERALD", "trial": "B-EMERALD", "papers": [ { "key": "P-EMERALD", "pmid": "35584336", "title": "Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35584336/", "doi": "10.1200/JCO.22.00338", "errata": [ { "pmid": "37364222", "title": "Erratum: Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.", "url": "https://pubmed.ncbi.nlm.nih.gov/37364222/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "EMERALD", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After CDK4/6 inhibitor, advanced", "population": "ER+, HER2− advanced breast cancer; ESR1 mutation detected in 47.8%", "claim": "Elacestrant vs standard endocrine therapy: PFS HR 0.70 in all patients and 0.55 in patients with ESR1 mutation.", "trialRecord": { "key": "B-EMERALD", "nct": "NCT03778931", "acronym": "EMERALD", "title": "Phase 3 Trial of Elacestrant Versus Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 478, "sponsor": "Stemline Therapeutics, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2019-05-10", "lastUpdate": "2025-09-15", "url": "https://clinicaltrials.gov/study/NCT03778931" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival by blinded independent central review, in all patients and in patients with detectable ESR1 mutations (co-primary)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "blinded independent central review", "quote": "This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. … Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable ESR1 mutations. … Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238)." }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.55, "ci_high": 0.88, "ci_level": "95%", "p": "P = .002", "endpoint": "PFS, all patients (co-primary; ESR1-mutated subgroup HR 0.55, 95% CI 0.39 to 0.77, P = .0005)", "quote": "PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 7.2, "grade3plus_control_pct": 3.1, "discontinuation_experimental_pct": 3.4, "discontinuation_control_pct": 0.9, "treatment_related_deaths": null, "quote": "Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively)." }, "takeaway_en": "In ER-positive/HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor, oral elacestrant was compared with standard endocrine monotherapy and prolonged progression-free survival (HR 0.70 in all patients and 0.55 in patients with ESR1 mutation); no landmark percentages were reported in the abstract. Treatment-related grade 3/4 adverse events occurred in 7.2% vs 3.1%, and any-grade nausea was more common with elacestrant (35.0% vs 18.8%).", "takeaway_ko": "CDK4/6 억제제 치료 후 진행한 ER 양성/HER2 음성 진행성 유방암 환자에서 경구 엘라세스트란트를 표준 내분비 단독요법과 비교했으며, 무진행생존기간이 연장되었습니다(전체 환자 HR 0.70, ESR1 변이 환자 HR 0.55). 초록에는 특정 시점의 생존율이 보고되지 않았습니다. 치료 관련 3/4등급 이상반응은 엘라세스트란트군 7.2%, 표준치료군 3.1%였고, 모든 등급의 오심도 엘라세스트란트군에서 더 흔했습니다(35.0% 대 18.8%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PADA1", "trial": "B-PADA1", "papers": [ { "key": "P-PADA1", "pmid": "36183733", "title": "Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial.", "journal": "Lancet Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36183733/", "doi": "10.1016/S1470-2045(22)00555-1", "errata": [] } ], "pages": [], "targets": [ "ESR1", "CDK4/6" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "PADA-1", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, during aromatase inhibitor + palbociclib", "population": "ER+, HER2− advanced breast cancer with rising blood ESR1 mutation and no progression", "claim": "Of 1,017 patients, 279 (27%) developed a rising ESR1 mutation in blood; 172 were randomised. Switching to fulvestrant plus palbociclib: PFS 11.9 vs 5.7 months (HR 0.61).", "trialRecord": { "key": "B-PADA1", "nct": "NCT03079011", "acronym": "PADA-1", "title": "PAlbociclib and Circulating Tumor DNA for ESR1 Mutation Detection", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1017, "sponsor": "UNICANCER", "sponsorClass": "OTHER", "collaborators": [ "Pfizer" ], "hasResults": false, "start": "2017-03-22", "lastUpdate": "2025-11-18", "url": "https://clinicaltrials.gov/study/NCT03079011" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival from random assignment in the intention-to-treat population (co-primary with grade 3 or worse haematological adverse events in all patients)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 172, "assessment": "investigator", "quote": "We did a randomised, open-label, phase 3 trial in 83 hospitals in France … The co-primary endpoints were investigator-assessed progression-free survival from random assignment, analysed in the intention-to-treat population (ie, all randomly assigned patients), and grade 3 or worse haematological adverse events in all patients … 172 (17%) were randomly assigned to treatment: 88 to switching to fulvestrant and palbociclib and 84 patients to continuing aromatase inhibitor and palbociclib." }, "effect": { "measure": "HR", "value": 0.61, "ci_low": 0.43, "ci_high": 0.86, "ci_level": null, "p": "p=0·0040", "endpoint": "Progression-free survival from random assignment (investigator-assessed)", "quote": "Median progression-free survival from random assignment was 11·9 months (95% CI 9·1-13·6) in the fulvestrant and palbociclib group versus 5·7 months (3·9-7·5) in the aromatase inhibitor and palbociclib group (stratified HR 0·61, 0·43-0·86; p=0·0040)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "One treatment-related death (pulmonary embolism) in step 1, before randomisation. No treatment-related deaths were reported in the randomised step 2.", "quote": "The most common grade 3 or worse adverse events in step 2 were neutropenia (35 [41·7%] of 84 patients in the aromatase inhibitor and palbociclib group vs 39 [44·3%] of 88 patients in the fulvestrant and palbociclib group) and lymphopenia (three [3·6%] vs four [4·5%]) … One death by pulmonary embolism in step 1 was declared as being treatment related." }, "takeaway_en": "In 172 patients with ER-positive, HER2-negative advanced breast cancer who developed a rising blood ESR1 mutation without disease progression during first-line aromatase inhibitor plus palbociclib, switching to fulvestrant plus palbociclib gave a median investigator-assessed progression-free survival of 11.9 months, compared with 5.7 months for continuing the same therapy (HR 0.61) in this open-label trial. Grade 3 or worse neutropenia was similar between arms (44.3% with the switch vs 41.7% with continuation), and the abstract does not report overall grade 3 or worse adverse event rates or discontinuation rates by arm.", "takeaway_ko": "아로마타제 억제제와 팔보시클립 1차 치료 중 질병 진행 없이 혈중 ESR1 변이가 상승한 ER 양성, HER2 음성 진행성 유방암 환자 172명을 대상으로 한 공개 라벨 시험입니다. 풀베스트란트와 팔보시클립으로 전환한 군의 연구자 평가 무진행생존기간 중앙값은 11.9개월로, 기존 치료를 지속한 군의 5.7개월보다 길었습니다(위험비 0.61). 3등급 이상 호중구감소증은 전환군 44.3%, 지속군 41.7%로 비슷했으며, 초록에는 군별 전체 3등급 이상 이상반응 및 치료 중단 비율이 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-SERENA6", "trial": "B-SERENA6", "papers": [ { "key": "P-SERENA6", "pmid": "40454637", "title": "First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454637/", "doi": "10.1056/NEJMoa2502929", "errata": [] }, { "key": "P-PM42442380", "pmid": "42442380", "title": "Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial.", "journal": "Lancet Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42442380/", "doi": "10.1016/S1470-2045(26)00287-1", "errata": [] } ], "pages": [], "targets": [ "ESR1", "CDK4/6" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "Overall survival is not reported in either abstract. The comparator continued the aromatase inhibitor after the ESR1 mutation emerged.", "label": "SERENA-6", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, during aromatase inhibitor + CDK4/6 inhibitor", "population": "HR+, HER2− advanced breast cancer with emerging ESR1 mutation in ctDNA", "claim": "Switching to camizestrant at ESR1 mutation emergence: PFS 16.0 vs 9.2 months (HR 0.44) at an interim analysis (median follow-up 12.6 months). At the extended analysis (median follow-up 23.5 months), PFS was 16.8 vs 9.2 months (HR 0.45, 95% CI 0.34-0.59) and second PFS was 25.7 vs 19.1 months (HR 0.63, 95% CI 0.46-0.86; p=0.0037).", "trialRecord": { "key": "B-SERENA6", "nct": "NCT04964934", "acronym": "SERENA-6", "title": "Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 315, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2021-06-30", "lastUpdate": "2026-09-23", "url": "https://clinicaltrials.gov/study/NCT04964934" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (RECIST 1.1)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 315, "assessment": "investigator", "quote": "This double-blind, placebo-controlled, randomised, phase 3 trial … the primary endpoint (investigator-assessed according to RECIST 1.1 progression-free survival) … 315 patients … were randomly assigned: 157 to camizestrant plus CDK4/6 inhibitor and 158 to aromatase inhibitor plus CDK4/6 inhibitor." }, "effect": { "measure": "HR", "value": 0.45, "ci_low": 0.34, "ci_high": 0.59, "ci_level": "95%", "p": "nominal p<0·0001", "endpoint": "Progression-free survival (extended descriptive analysis, median follow-up 23.5 months; interim primary analysis HR 0.44, 95% CI 0.31 to 0.60, P<0.0001)", "quote": "After a median follow-up of 23·5 months (IQR 17·9-32·1; data cutoff Jan 2, 2026), median progression-free survival was 16·8 months (95% CI 14·7-19·4) with camizestrant plus CDK4/6 inhibitor versus 9·2 months (7·2-9·7) with aromatase inhibitor plus CDK4/6 inhibitor (hazard ratio [HR] 0·45 [95% CI 0·34-0·59]; nominal p<0·0001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 1.3, "discontinuation_control_pct": 1.9, "treatment_related_deaths": "Three deaths considered possibly treatment-related: 1 in the camizestrant group (sudden death) and 2 in the aromatase inhibitor group (sepsis, ileus)", "quote": "The frequency of discontinuation because of adverse events was 1.3% with camizestrant and 1.9% with an aromatase inhibitor. … There were three deaths considered by the trial investigator to be possibly related to treatment (camizestrant plus CDK4/6 inhibitor group: sudden death, possibly related to camizestrant; aromatase inhibitor plus CDK4/6 inhibitor group: sepsis, possibly related to abemaciclib, and ileus, possibly related to letrozole).", "quote_note": "Lancet Oncol 2026 extended; NEJM 2025 interim" }, "takeaway_en": "In 315 patients with ER-positive, HER2-negative advanced breast cancer who developed an ESR1 mutation in ctDNA without radiologic progression during first-line aromatase inhibitor plus CDK4/6 inhibitor, switching to camizestrant while continuing the CDK4/6 inhibitor gave a median PFS of 16.8 vs 9.2 months (HR 0.45) at the extended analysis, with median follow-up of 23.5 months. Median second PFS was 25.7 vs 19.1 months (HR 0.63), and grade 3-4 neutropenia was more frequent with camizestrant (27% vs 17%), while discontinuation due to adverse events was low in both arms (1.3% vs 1.9%).", "takeaway_ko": "1차 치료로 아로마타제 억제제와 CDK4/6 억제제를 투여받던 중 순환종양DNA(ctDNA)에서 ESR1 변이가 새로 검출되었으나 영상학적 진행은 없는 ER 양성/HER2 음성 진행성 유방암 환자 315명을 대상으로 했습니다. 이들 중 CDK4/6 억제제를 유지하며 카미제스트란트로 전환한 군의 무진행생존기간 중앙값은 16.8개월로, 아로마타제 억제제 지속군의 9.2개월보다 길었습니다(위험비 0.45, 연장 분석, 추적관찰 중앙값 23.5개월). 2차 무진행생존기간 중앙값은 25.7개월 대 19.1개월이었습니다(위험비 0.63). 3–4등급 호중구감소증은 카미제스트란트군에서 더 흔했고(27% 대 17%), 이상반응으로 인한 투약 중단은 양군 모두 낮았습니다(1.3% 대 1.9%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-POSITIVE", "trial": null, "papers": [ { "key": "P-PM37133584", "pmid": "37133584", "title": "Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37133584/", "doi": "10.1056/NEJMoa2212856", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "This was not a randomized trial: it was a single-group study, and the comparison with an external control cohort may be affected by selection and other differences between the groups. Median follow-up was 41 months, so the abstract supports only short-term safety, and the authors state that longer follow-up is critical. Most participants had stage I or II disease and were described as select women, so the results may not apply to higher-risk patients. The abstract does not report outcomes by specific endocrine regimen or by subgroup. Harms: The abstract reports breast cancer events (44 at 1638 patient-years) as the safety outcome and gives no other adverse-event data.", "label": "POSITIVE (NCT02308085)", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Young women with previous hormone receptor-positive early breast cancer who temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. This was a single-group trial compared with an external control cohort.", "population": "516 women aged 42 years or younger with stage I, II, or III disease who had received adjuvant endocrine therapy for 18 to 30 months and desired pregnancy. Median age was 37 years, median time from diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease.", "claim": "The primary end point was the number of breast cancer events during follow-up, against a prespecified safety threshold of 46 events over 1600 patient-years. At 1638 patient-years (median follow-up 41 months), 44 patients had a breast cancer event, which did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% CI, 6.3 to 11.6) with treatment interruption and 9.2% (95% CI, 7.6 to 10.8) in the external control cohort. Among 497 women followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "takeaway_en": "In this single-group trial, women with hormone receptor-positive early breast cancer who paused endocrine therapy after 18 to 30 months to try to conceive had 44 breast cancer events over 1638 patient-years, below the prespecified safety threshold of 46. Their 3-year event rate (8.9%) was similar to an external control cohort (9.2%), and most achieved a pregnancy, though longer-term safety remains unknown.", "takeaway_ko": "이 단일군 임상시험에서 호르몬 수용체 양성 조기 유방암 여성들은 내분비요법을 18~30개월 받은 뒤 임신 시도를 위해 일시 중단했습니다. 1638 환자-년 동안 유방암 사건은 44건으로, 사전에 정한 안전성 기준치인 46건보다 적었습니다. 3년 유방암 사건 발생률은 8.9%로 외부 대조 코호트(9.2%)와 비슷했고 대부분이 임신에 성공했지만, 장기적인 안전성은 아직 알 수 없습니다.", "landmark": [], "effect": {}, "harms": {}, "design": {}, "certainty": null, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code" } }, { "id": "U-POEMS", "trial": null, "papers": [ { "key": "P-PM25738668", "pmid": "25738668", "title": "Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25738668/", "doi": "10.1056/NEJMoa1413204", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Primary end-point data were missing for many evaluable patients: only 135 of 218 had complete data. The authors state that this weakens interpretation, even though missingness did not differ by treatment group or stratification factors. The confidence interval for the primary odds ratio is wide (0.09 to 0.97). The pregnancy and survival findings are secondary end points with borderline P values, so they should not be read as confirmatory. The trial enrolled only hormone-receptor-negative disease, so the results do not establish effects in hormone-receptor-positive patients.", "label": "POEMS/S0230 (goserelin for ovarian protection)", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant or standard chemotherapy for operable breast cancer in premenopausal women; GnRH agonist goserelin given alongside chemotherapy to protect ovarian function.", "population": "257 premenopausal women with operable hormone-receptor-negative breast cancer were randomised. 218 were eligible and evaluable at baseline, and 135 had complete primary end-point data.", "claim": "Among the 135 patients with complete primary end-point data, the 2-year ovarian failure rate was 8% with goserelin plus chemotherapy versus 22% with chemotherapy alone (odds ratio 0.30; 95% CI 0.09 to 0.97; P=0.04). Ovarian failure was defined as no menses in the preceding 6 months plus FSH in the postmenopausal range. Sensitivity analyses for missing data were consistent with the main finding. In secondary end points among the 218 evaluable patients, pregnancy occurred more often with goserelin (21% vs. 11%, P=0.03), and disease-free survival (P=0.04) and overall survival (P=0.05) were also improved.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Ovarian failure at 2 years (no menses for 6 months and postmenopausal FSH)", "primary_endpoint_type": "other", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 257, "assessment": "not stated", "quote": "We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group).", "quote_note": "Only 135 women had complete primary end-point data; the authors note that missing data weaken interpretation." }, "effect": { "measure": "OR", "value": 0.3, "ci_low": 0.09, "ci_high": 0.97, "ci_level": "95%", "p": "P=0.04", "endpoint": "Ovarian failure at 2 years (goserelin vs chemotherapy alone), among 135 women with complete data", "quote": "Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04)." }, "landmark": [ { "endpoint": "Ovarian failure", "timepoint": "2 years", "experimental_pct": 8, "control_pct": 22, "higher_is_better": false, "experimental_arm": "Chemotherapy plus goserelin", "control_arm": "Chemotherapy alone", "quote": "Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group", "difference_pp": -14, "nnt": 8 }, { "endpoint": "Pregnancy", "timepoint": "during follow-up", "experimental_pct": 21, "control_pct": 11, "higher_is_better": true, "experimental_arm": "Chemotherapy plus goserelin", "control_arm": "Chemotherapy alone", "quote": "Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03)", "difference_pp": 10, "nnt": 10 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null }, "takeaway_en": "In premenopausal women with hormone-receptor-negative breast cancer, adding goserelin to chemotherapy was associated with less ovarian failure at 2 years (8% vs. 22%) among patients with complete data. Pregnancies were also more frequent in the goserelin group, but substantial missing data and the secondary nature of the fertility and survival results limit certainty.", "takeaway_ko": "호르몬 수용체 음성 유방암 폐경 전 여성에서 항암화학요법에 고세렐린을 추가했을 때, 자료가 완전한 환자들 중 2년 시점 난소부전이 더 적었습니다(8% 대 22%). 고세렐린군에서 임신도 더 많았지만, 결측 자료가 많고 임신·생존 결과는 이차 평가변수여서 확실성에는 한계가 있습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "moderate", "reasons": [ "fewer than 300 patients randomized" ] } } }, { "id": "U-PROMISEGIM6", "trial": null, "papers": [ { "key": "P-PM21771987", "pmid": "21771987", "title": "Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial.", "journal": "JAMA", "year": "2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21771987/", "doi": "10.1001/jama.2011.991", "errata": [] }, { "key": "P-PM34850043", "pmid": "34850043", "title": "Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients.", "journal": "J Natl Cancer Inst", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/34850043/", "doi": "10.1093/jnci/djab213", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The trial was open-label. The primary analysis used imputed values for missing data. The ovarian failure endpoint was assessed only at 1 year after chemotherapy. DFS, OS and pregnancy were post hoc endpoints the trial was not designed to test, so the absence of a difference does not prove equivalence; this also applies to the hormone receptor-positive subgroup (DFS HR 1.02, OS HR 1.12). Pregnancy numbers were small (9 vs 4; HR = 2.14, 95% CI 0.66 to 6.92), so no fertility benefit is shown. Harms: The abstracts report no short-term adverse event data for triptorelin; long-term DFS and OS showed no observed difference, including in hormone receptor-positive disease, in post hoc analyses.", "label": "PROMISE-GIM6", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Randomized, open-label, phase 3 superiority trial at 16 sites in Italy (enrolment October 2003 to January 2008). It compared (neo)adjuvant chemotherapy alone with chemotherapy plus the GnRH analogue triptorelin given for ovarian protection.", "population": "281 premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy; 80.4% had hormone receptor-positive disease.", "claim": "The primary endpoint was early menopause, defined as no resumption of menses plus postmenopausal FSH and estradiol levels 1 year after the last chemotherapy cycle. It occurred in 25.9% of the chemotherapy-alone group (n=133) and 8.9% of the chemotherapy plus triptorelin group (n=148). The absolute difference was -17% (95% CI, -26% to -7.9%; P < .001), and the odds ratio was 0.28 (95% CI, 0.14 to 0.59). In post hoc long-term analyses at a median follow-up of 12.4 years, neither 12-year DFS (65.7% vs 69.2%; HR = 1.16, 95% CI 0.76 to 1.77) nor 12-year OS (81.2% vs 81.3%; HR = 1.17, 95% CI 0.67 to 2.03) differed between arms.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Early menopause 1 year after the last chemotherapy cycle", "primary_endpoint_type": "other", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 281, "assessment": "not stated", "quote": "The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008." }, "effect": { "measure": "difference", "value": -17, "ci_low": -26, "ci_high": -7.9, "ci_level": "95%", "p": "P < .001", "endpoint": "Early menopause at 12 months after chemotherapy, absolute difference (triptorelin minus chemotherapy alone, percentage points)", "quote": "the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001)." }, "landmark": [ { "endpoint": "Early menopause", "timepoint": "12 months after the last chemotherapy cycle", "experimental_pct": 8.9, "control_pct": 25.9, "higher_is_better": false, "experimental_arm": "Chemotherapy plus triptorelin", "control_arm": "Chemotherapy alone", "quote": "the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group", "difference_pp": -17, "nnt": 6 }, { "endpoint": "Disease-free survival", "timepoint": "12 years", "experimental_pct": 65.7, "control_pct": 69.2, "higher_is_better": true, "experimental_arm": "Chemotherapy plus triptorelin", "control_arm": "Chemotherapy alone", "quote": "No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77)", "difference_pp": -3.5, "nnt": null, "nnt_label": "favours control", "nnh": 29, "quote_note": "Long-term paper (median follow-up 12.4 years); the difference is not statistically significant." }, { "endpoint": "Overall survival", "timepoint": "12 years", "experimental_pct": 81.2, "control_pct": 81.3, "higher_is_better": true, "experimental_arm": "Chemotherapy plus triptorelin", "control_arm": "Chemotherapy alone", "quote": "in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed", "difference_pp": -0.1, "nnt": null, "nnt_label": "favours control", "nnh": 1000, "quote_note": "Long-term paper (median follow-up 12.4 years); the difference is not statistically significant." } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null }, "takeaway_en": "In this Italian trial, adding triptorelin during chemotherapy reduced 1-year chemotherapy-induced early menopause from 25.9% to 8.9% in premenopausal women with early breast cancer. Post hoc follow-up over about 12 years showed no observed difference in disease-free or overall survival, while the small number of pregnancies does not establish a fertility benefit.", "takeaway_ko": "이 이탈리아 임상시험에서는 폐경 전 조기 유방암 환자에게 항암치료 중 트립토렐린을 추가했을 때, 항암치료 1년 후 조기 폐경이 25.9%에서 8.9%로 줄었습니다. 약 12년간의 사후 추적 분석에서 무병생존과 전체생존에는 차이가 관찰되지 않았으나, 임신 건수가 적어 생식능력 보존 효과는 입증되지 않았습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "fewer than 300 patients randomized" ] } } }, { "id": "U-STOCKHOLMHRT", "trial": null, "papers": [ { "key": "P-PM15812079", "pmid": "15812079", "title": "Menopausal hormone therapy after breast cancer: the Stockholm randomized trial.", "journal": "J Natl Cancer Inst", "year": "2005", "url": "https://pubmed.ncbi.nlm.nih.gov/15812079/", "doi": "10.1093/jnci/dji071", "errata": [] }, { "key": "P-PM22892060", "pmid": "22892060", "title": "Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial.", "journal": "Eur J Cancer", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/22892060/", "doi": "10.1016/j.ejca.2012.07.003", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The trial was closed early, so it is underpowered, and the authors state the data do not allow firm conclusions. The hazard ratio confidence interval (0.9-1.9) does not exclude a meaningful increase in breast cancer events. The contralateral cancer excess rests on small numbers. HABITS showed higher recurrence with HRT (RH = 3.3, 95% CI = 1.5 to 7.4), and the between-trial heterogeneity (P = .02) is only a suggestion that progestogen dose or regimen matters, not proof. Harms: Contralateral breast cancer was more frequent with HRT (14 vs four cases); no increase in mortality or new primary malignancies was reported.", "label": "Stockholm HRT after breast cancer trial", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Sweden. The randomised trial started in 1997 and was stopped in 2003 after the parallel HABITS trial reported increased recurrence. Long-term follow-up was 10.8 years.", "population": "Disease-free women with a history of early-stage breast cancer, randomised to menopausal hormone replacement therapy designed to minimise progestogen dose (n=188) or no HRT (n=190).", "claim": "At a median follow-up of 4.1 years, HRT was not associated with breast cancer recurrence (RH = 0.82, 95% CI = 0.35 to 1.9). After 10.8 years, new breast cancer events still did not differ significantly: 60 with HRT versus 48 among controls (HR=1.3; 95% CI=0.9-1.9). Contralateral breast cancers were more frequent with HRT, 14 versus four (HR=3.6; 95% CI=1.2-10.9; p=0.013). No differences in mortality or new primary malignancies were found.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "New breast cancer events", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 378, "assessment": "not stated", "quote": "Disease-free women with a history of breast cancer were randomised to HRT (n=188) or no HRT (n=190). The trial was stopped in 2003 when another Swedish study (HABITS, the Hormonal Replacement After Breast Cancer - Is it Safe?) reported increased recurrence.", "quote_note": "The 378 total is from the 2005 report." }, "effect": { "measure": "HR", "value": 1.3, "ci_low": 0.9, "ci_high": 1.9, "ci_level": "95%", "p": null, "endpoint": "New breast cancer events after 10.8 years (HRT vs no HRT)", "quote": "After 10.8 years of follow-up, there was no difference in new breast cancer events: 60 in the HRT group versus 48 among controls (hazard ratio (HR)=1.3; 95% confidence interval (CI)=0.9-1.9)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "There were 14 contra-lateral breast cancers in the HRT group and four in the control group (HR=3.6; 95% CI=1.2-10.9; p=0.013). No differences in mortality or new primary malignancies were found." }, "takeaway_en": "In this early-closed Stockholm trial of low-progestogen HRT after breast cancer, overall new breast cancer events did not differ significantly from no HRT over about 11 years, and mortality was similar. There were more contralateral breast cancers with HRT, and a parallel trial with higher progestogen exposure found increased recurrence.", "takeaway_ko": "조기 종료된 스톡홀름 시험에서 유방암 생존자에게 프로게스토겐 용량을 최소화한 호르몬 대체요법을 시행했습니다. 약 11년 동안 새로운 유방암 사건 전체는 비투여군과 유의한 차이가 없었고, 사망률도 비슷했습니다. 다만 호르몬 대체요법군에서 반대측 유방암이 더 많았으며, 프로게스토겐 노출이 더 높았던 병행 시험(HABITS)에서는 재발이 증가했습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] } } }, { "id": "U-HABITS", "trial": null, "papers": [ { "key": "P-PM18364505", "pmid": "18364505", "title": "Increased risk of recurrence after hormone replacement therapy in breast cancer survivors.", "journal": "J Natl Cancer Inst", "year": "2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18364505/", "doi": "10.1093/jnci/djn058", "errata": [ { "pmid": null, "title": "J Natl Cancer Inst. 2008 May 7;100(9):685", "url": "https://pubmed.ncbi.nlm.nih.gov/18364505/", "reviewed": false, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "There was no placebo, and the trial was stopped early, which may exaggerate the size of the effect. The trial was small with few events, so the lack of a difference in breast cancer death or metastasis (P = .51) does not show that HT is safe for survival. Most women received estradiol plus norethisterone, so the results may not apply to other hormone regimens. The abstract gives no analyses by tumour receptor status or concurrent endocrine therapy. Harms: HT was associated with more new breast cancer events (39 vs 17); the abstract reports no other adverse events.", "label": "HABITS", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Menopausal symptom management in women previously treated for breast cancer. The randomized, non-placebo-controlled noninferiority trial was stopped early; this report gives extended follow-up.", "population": "Breast cancer survivors with menopausal symptoms, randomly assigned to hormone replacement therapy (HT) or best management without hormones. Most HT users were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone.", "claim": "Of 447 women randomized, 442 were followed for a median of 4 years. A new breast cancer event occurred in thirty-nine of 221 women on HT and 17 of 221 controls (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidence at 5 years was 22.2% with HT and 8.0% with control. Breast cancer deaths and distant metastases did not differ significantly: six deaths and six women with metastases with HT versus five and four with control (P = .51).", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "New breast cancer event", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "open-label", "n_randomized": 447, "assessment": "not stated", "quote": "HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. … Of the 447 women randomly assigned, 442 could be followed for a median of 4 years.", "quote_note": "The abstract says non-placebo-controlled; IATHEON reads that as open-label for the certainty rule. The trial was stopped early." }, "effect": { "measure": "HR", "value": 2.4, "ci_low": 1.3, "ci_high": 4.2, "ci_level": "95%", "p": null, "endpoint": "New breast cancer event (hormone therapy vs best management without hormones)", "quote": "Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2)." }, "landmark": [ { "endpoint": "New breast cancer event (cumulative incidence)", "timepoint": "5 years", "experimental_pct": 22.2, "control_pct": 8, "higher_is_better": false, "experimental_arm": "Hormone therapy", "control_arm": "Best management without hormones", "quote": "Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm.", "difference_pp": 14.2, "nnt": null, "nnt_label": "favours control", "nnh": 8 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null }, "takeaway_en": "In this randomized trial of breast cancer survivors, hormone replacement therapy was associated with about 2.4 times the hazard of a new breast cancer event, with 5-year cumulative incidence of 22.2% versus 8.0%. Breast cancer deaths and metastases were few and not significantly different, and the trial was stopped early.", "takeaway_ko": "유방암 생존자를 대상으로 한 이 무작위 시험에서 호르몬 대체요법은 새로운 유방암 사건의 위험을 약 2.4배 높였고, 5년 누적 발생률은 22.2% 대 8.0%였습니다. 유방암 사망과 전이는 건수가 적었고 두 군 간에 유의한 차이가 없었으며, 시험은 조기 중단되었습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] } } }, { "id": "U-LIBERATE", "trial": null, "papers": [ { "key": "P-PM19167925", "pmid": "19167925", "title": "Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.", "journal": "Lancet Oncol", "year": "2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19167925/", "doi": "10.1016/S1470-2045(08)70341-3", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Median follow-up was 3.1 years, so longer-term recurrence and survival effects are not established by this abstract. Mortality, cardiovascular events and gynaecological cancers were reported as not different, but event counts were small and the trial was not designed to test these outcomes. The abstract does not report whether the recurrence increase differed by oestrogen-receptor status or concurrent tamoxifen or aromatase-inhibitor use. Effect sizes for symptom and bone-density benefits are not given. Harms: Beyond the higher recurrence risk, tibolone did not differ from placebo in mortality (72 vs 63), cardiovascular events (14 vs 10) or gynaecological cancers (10 vs 10).", "label": "Tibolone vs placebo in breast-cancer survivors with vasomotor symptoms (NCT00408863)", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Double-blind, randomised, non-inferiority trial at 245 centres in 31 countries. Women were enrolled between July 11, 2002, and Dec 20, 2004. Funded by Schering-Plough (formerly NV Organon).", "population": "Women surgically treated for histologically confirmed T1-3N0-2M0 breast cancer who had vasomotor symptoms. Of 3148 randomised, 3098 were in the ITT analysis. Mean age was 52.7 years and mean time since surgery 2.1 years. 58% were node positive and 71% oestrogen-receptor positive. At entry, 67% used tamoxifen and 6.5% used aromatase inhibitors.", "claim": "The trial aimed to show that tibolone 2.5 mg daily was non-inferior to placebo for breast-cancer recurrence, including contralateral cancer, with a non-inferiority margin of HR 1.278. It failed. After a median follow-up of 3.1 years, recurrence occurred in 237 of 1556 (15.2%) women on tibolone versus 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Per-protocol results were similar: 16.7% vs 11.4% (HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Vasomotor symptoms and bone-mineral density improved significantly with tibolone.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Breast cancer recurrence, including contralateral breast cancer", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "double-blind", "n_randomized": 3148, "assessment": "not stated", "quote": "Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. … Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group)." }, "effect": { "measure": "HR", "value": 1.4, "ci_low": 1.14, "ci_high": 1.7, "ci_level": "95%", "p": "p=0.001", "endpoint": "Breast cancer recurrence (tibolone vs placebo; non-inferiority margin HR 1.278)", "quote": "After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001)." }, "landmark": [ { "endpoint": "Breast cancer recurrence", "timepoint": "median follow-up 3.1 years", "experimental_pct": 15.2, "control_pct": 10.7, "higher_is_better": false, "experimental_arm": "Tibolone 2.5 mg daily", "control_arm": "Placebo", "quote": "237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo", "difference_pp": 4.5, "nnt": null, "nnt_label": "favours control", "nnh": 23 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively)." }, "takeaway_en": "In women treated for breast cancer who had hot flushes, tibolone raised breast-cancer recurrence compared with placebo (15.2% vs 10.7% at a median 3.1 years) and so failed to show non-inferiority. It did relieve vasomotor symptoms and prevent bone loss.", "takeaway_ko": "안면홍조가 있는 유방암 치료 후 여성에서 티볼론은 위약보다 유방암 재발을 늘렸습니다(중앙 추적 3.1년 시점 15.2% 대 10.7%). 따라서 비열등성을 입증하지 못했습니다. 다만 혈관운동 증상은 완화되었고 골소실은 예방되었습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] } } }, { "id": "U-OASIS4", "trial": null, "papers": [ { "key": "P-PM40454634", "pmid": "40454634", "title": "Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454634/", "doi": "10.1056/NEJMoa2415566", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "The placebo comparison lasted only 12 weeks, and the abstract reports no controlled efficacy data for the 40-week extension. The placebo group also improved substantially, so the effect beyond placebo was about 3.4 to 3.5 fewer episodes per day. The abstract reports no breast cancer outcomes, no subgroup results by endocrine agent or menopausal status, and no data for women over 70. The trial was industry funded. Harms: During weeks 1 through 12, adverse events occurred in 69.8% of the elinzanetant group versus 62.0% of the placebo group, most commonly headache, fatigue, and somnolence; serious adverse events occurred in 2.5% versus 0.6%.", "label": "OASIS-4", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Phase 3 randomized trial of once-daily elinzanetant 120 mg for 52 weeks versus placebo for 12 weeks followed by elinzanetant for 40 weeks, allocated 2:1. Funded by Bayer.", "population": "Women aged 18 to 70 years with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention. 316 were assigned to elinzanetant and 158 to placebo-elinzanetant.", "claim": "Baseline mean daily frequency of moderate-to-severe vasomotor symptoms was 11.4 and 11.5 episodes. Both primary end points favored elinzanetant over placebo. At week 4, the least-squares mean difference in change from baseline was -3.5 episodes (95% CI, -4.4 to -2.6; P<0.001), with changes of -6.5 versus -3.0 episodes. At week 12, the difference was -3.4 episodes (95% CI, -4.2 to -2.5; P<0.001), with changes of -7.8 versus -4.2 episodes.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Change in daily frequency of moderate-to-severe vasomotor symptoms to week 4 and week 12", "primary_endpoint_type": "other", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "We performed a phase 3 trial involving women 18 to 70 years of age with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention. Women were randomly assigned in a 2:1 ratio to receive once-daily elinzanetant at a dose of 120 mg for 52 weeks or once-daily placebo for 12 weeks followed by once-daily elinzanetant at a dose of 120 mg for 40 weeks. … A total of 316 participants were assigned to the elinzanetant group and 158 to the placebo-elinzanetant group." }, "effect": { "measure": "difference", "value": -3.4, "ci_low": -4.2, "ci_high": -2.5, "ci_level": "95%", "p": "P<0.001", "endpoint": "Least-squares mean difference in daily moderate-to-severe vasomotor symptoms, baseline to week 12 (episodes per day; week 4: -3.5)", "quote": "At week 12, the mean change was -7.8 episodes (95% CI, -8.5 to -7.1) among those receiving elinzanetant and -4.2 episodes (95% CI, -5.2 to -3.2) among those receiving placebo (least-squares mean difference, -3.4 episodes; 95% CI, -4.2 to -2.5; P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "During weeks 1 through 12, a total of 220 participants (69.8%) receiving elinzanetant and 98 (62.0%) receiving placebo reported at least one adverse event that occurred while receiving elinzanetant or placebo, with the most common being headache, fatigue, and somnolence. Serious adverse events occurred during weeks 1 through 12 in 8 participants (2.5%) receiving elinzanetant and 1 participant (0.6%) receiving placebo." }, "takeaway_en": "In women with endocrine-therapy-related hot flashes, elinzanetant reduced moderate-to-severe episodes by about 3.5 more per day than placebo at weeks 4 and 12. Serious adverse events were few but more frequent with elinzanetant, and the abstract gives no long-term controlled or cancer outcome data.", "takeaway_ko": "내분비요법으로 안면홍조를 겪는 여성에서 엘린자네탄트는 4주와 12주에 중등도-중증 안면홍조를 위약보다 하루 약 3.5회 더 줄였습니다. 중대한 이상반응은 적었지만 엘린자네탄트군에서 더 많았고, 초록에는 장기 대조 효과나 암 관련 결과 자료가 없습니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] } } }, { "id": "U-NSABPP1", "trial": null, "papers": [ { "key": "P-PM16288118", "pmid": "16288118", "title": "Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study.", "journal": "J Natl Cancer Inst", "year": "2005", "url": "https://pubmed.ncbi.nlm.nih.gov/16288118/", "doi": "10.1093/jnci/dji372", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The trial was unblinded after the initial positive results, and the authors acknowledge this may have biased the updated estimates. Tamoxifen did not change death or ischemic heart disease, so this report shows no survival benefit. Differences in net benefit by age, race and breast cancer risk category come from comparisons of estimated net benefit, not formal tests of treatment interaction. The abstract gives no absolute rates for the harms. Harms: Tamoxifen increased the risks of stroke, deep-vein thrombosis, cataracts, thromboembolic events and endometrial cancer, with relative risks similar to those initially reported.", "label": "NSABP P-1 (Breast Cancer Prevention Trial), 7-year update", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Primary prevention of breast cancer in women at increased risk; updated follow-up after the trial was unblinded", "population": "13,388 women at increased risk for breast cancer, randomly assigned to placebo or tamoxifen for 5 years", "claim": "After 7 years of follow-up, tamoxifen reduced the cumulative rate of invasive breast cancer from 42.5 to 24.8 per 1000 women compared with placebo (RR = 0.57, 95% CI = 0.46 to 0.70). Noninvasive breast cancer fell from 15.8 to 10.2 per 1000 women (RR = 0.63, 95% CI = 0.45 to 0.89). Osteoporotic fractures were also reduced (RR = 0.68, 95% CI = 0.51 to 0.92). These effect sizes were similar to those in the initial report.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07", "added": "2026-11-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive breast cancer", "primary_endpoint_type": "other", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 13388, "assessment": "not stated", "quote": "Women (n = 13,388) were randomly assigned to receive placebo or tamoxifen for 5 years.", "quote_note": "Placebo-controlled; the abstract says the trial was later unblinded because of the positive results." }, "effect": { "measure": "RR", "value": 0.57, "ci_low": 0.46, "ci_high": 0.7, "ci_level": "95%", "p": null, "endpoint": "Invasive breast cancer after 7 years (tamoxifen vs placebo; 24.8 vs 42.5 per 1000 women)", "quote": "After 7 years of follow-up, the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group (RR = 0.57, 95% CI = 0.46 to 0.70)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Relative risks of stroke, deep-vein thrombosis, and cataracts (which increased with tamoxifen) and of ischemic heart disease and death (which were not changed with tamoxifen) were also similar to those initially reported. Risks of pulmonary embolism were approximately 11% lower than in the original report, and risks of endometrial cancer were about 29% higher, but these differences were not statistically significant." }, "takeaway_en": "In women at increased risk, tamoxifen versus placebo lowered the 7-year cumulative rate of invasive breast cancer from 42.5 to 24.8 per 1000 women (RR 0.57) and also reduced noninvasive breast cancer and osteoporotic fractures. Death and ischemic heart disease were unchanged, while stroke, deep-vein thrombosis, cataracts, thromboembolic events and endometrial cancer increased, so the net benefit varies by age, race and baseline risk.", "takeaway_ko": "유방암 위험이 높은 여성에서 타목시펜은 위약보다 7년 누적 침윤성 유방암 발생을 여성 1000명당 42.5명에서 24.8명으로 낮췄고(상대위험 0.57), 비침윤성 유방암과 골다공증성 골절도 줄였습니다. 사망과 허혈성 심질환은 차이가 없었고 뇌졸중·심부정맥혈전증·백내장·혈전색전증·자궁내막암은 늘어, 실제 이득은 나이·인종·기저 위험에 따라 달라집니다.", "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat or harm and certainty computed by code", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] } } }, { "id": "U-EMBER3", "trial": "B-EMBER3", "papers": [ { "key": "P-EMBER3", "pmid": "39660834", "title": "Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39660834/", "doi": "10.1056/NEJMoa2410858", "errata": [] }, { "key": "P-PM41391667", "pmid": "41391667", "title": "Imlunestrant with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase III EMBER-3 trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41391667/", "doi": "10.1016/j.annonc.2025.11.018", "errata": [] } ], "pages": [], "targets": [ "ESR1", "CDK4/6" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "Overall survival is an interim analysis and did not cross its significance boundary in the ESR1-mutated comparison.", "label": "EMBER-3", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "After endocrine therapy, advanced", "population": "ER+, HER2− advanced breast cancer", "claim": "Imlunestrant vs standard therapy: PFS 5.5 vs 3.8 months with ESR1 mutation, but 5.6 vs 5.5 months overall (HR 0.87). Imlunestrant plus abemaciclib vs imlunestrant: 9.4 vs 5.5 months. At the updated analysis (median follow-up 28.5 months), imlunestrant plus abemaciclib vs imlunestrant PFS was 10.9 vs 5.5 months (HR 0.59, 95% CI 0.47-0.74); in ESR1-mutated patients, interim OS was 34.5 vs 23.1 months with imlunestrant vs standard therapy (HR 0.60, 95% CI 0.43-0.86), but the significance boundary was not reached.", "trialRecord": { "key": "B-EMBER3", "nct": "NCT04975308", "acronym": "EMBER-3", "title": "A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 874, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2021-10-04", "lastUpdate": "2026-07-22", "url": "https://clinicaltrials.gov/study/NCT04975308" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (three primary comparisons: imlunestrant vs standard therapy in patients with ESR1 mutations; imlunestrant vs standard therapy in all patients; imlunestrant-abemaciclib vs imlunestrant in all concurrently randomized patients)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 874, "assessment": "investigator", "quote": "In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy … Primary end points were investigator-assessed progression-free survival … Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib." }, "effect": { "measure": "HR", "value": 0.59, "ci_low": 0.47, "ci_high": 0.74, "ci_level": "95%", "p": "nominal P < 0.0001", "endpoint": "Updated PFS, imlunestrant-abemaciclib vs imlunestrant, all patients regardless of ESR1 mutation (median follow-up 28.5 months)", "quote": "Notably, in all patients regardless of ESR1m, the median PFS of imlunestrant-abemaciclib versus imlunestrant was 10.9 versus 5.5 months (HR 0.59, 95% CI 0.47-0.74, nominal P < 0.0001).", "quote_note": "Ann Oncol 2026 updated analysis; primary analysis reported HR 0.57, 95% CI 0.44 to 0.73" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 48.6, "grade3plus_control_pct": 17.1, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib." }, "takeaway_en": "In ER-positive, HER2-negative advanced breast cancer after aromatase inhibitor therapy (with or without a CDK4/6 inhibitor), imlunestrant plus abemaciclib prolonged progression-free survival versus imlunestrant alone (updated median 10.9 vs 5.5 months; HR 0.59). Imlunestrant alone was better than standard endocrine therapy only in ESR1-mutated tumors (median 5.5 vs 3.8 months; interim overall survival HR 0.60, which did not reach the significance boundary), and grade 3 or higher adverse events occurred in 48.6% with the combination versus 17.1% with imlunestrant and 20.7% with standard therapy.", "takeaway_ko": "아로마타제 억제제 치료(CDK4/6 억제제 병용 여부 무관) 후 재발하거나 진행한 ER 양성, HER2 음성 진행성 유방암에서 imlunestrant와 abemaciclib 병용은 imlunestrant 단독에 비해 무진행생존기간을 연장했습니다(업데이트 분석 중앙값 10.9개월 대 5.5개월, HR 0.59). imlunestrant 단독은 ESR1 변이 환자에서만 표준 내분비요법보다 우수했으며(중앙값 5.5개월 대 3.8개월, 중간 전체생존 HR 0.60이나 유의성 경계에는 도달하지 못함), 3등급 이상 이상반응은 병용군 48.6%, imlunestrant 단독군 17.1%, 표준요법군 20.7%에서 발생했습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-VIKTORIA1", "trial": null, "papers": [ { "key": "P-PM41802242", "pmid": "41802242", "title": "VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.", "journal": "J Clin Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41802242/", "doi": "10.1200/JCO-25-02643", "errata": [ { "pmid": "42241670", "title": "Erratum: VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/42241670/", "reviewed": false, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PIK3CA", "CDK4/6" ], "biomarkers": [ "BM-PI3K", "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Only the PIK3CA wild-type comparison is reported; overall survival is not reported in the abstract, and follow-up is short. Grade 3 or higher neutropenia occurred in 62.3% with the triplet.", "label": "VIKTORIA-1 (PIK3CA wild-type)", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After CDK4/6 inhibitor plus aromatase inhibitor, advanced", "population": "HR+, HER2−, PIK3CA wild-type advanced breast cancer", "claim": "Gedatolisib, palbociclib and fulvestrant vs fulvestrant: PFS by blinded independent central review 9.3 vs 2.0 months (HR 0.24, 95% CI 0.17-0.35). Gedatolisib plus fulvestrant vs fulvestrant: 7.4 vs 2.0 months (HR 0.33, 95% CI 0.24-0.48). Median follow-up 10.1 months.", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by blinded independent central review (gedatolisib triplet vs fulvestrant and gedatolisib doublet vs fulvestrant)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 392, "assessment": "blinded independent central review", "quote": "This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) … Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. … A total of 392 patients were randomly assigned 1:1:1." }, "effect": { "measure": "HR", "value": 0.24, "ci_low": 0.17, "ci_high": 0.35, "ci_level": "95%", "p": "P < .001", "endpoint": "Progression-free survival (BICR), gedatolisib triplet vs fulvestrant", "quote": "The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 2.3, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients." }, "takeaway_en": "In HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer that progressed after a CDK4/6 inhibitor plus an aromatase inhibitor, median progression-free survival by blinded central review was 9.3 months with gedatolisib-palbociclib-fulvestrant versus 2.0 months with fulvestrant alone (HR 0.24, 95% CI 0.17 to 0.35), and 7.4 months with gedatolisib-fulvestrant (HR 0.33, 95% CI 0.24 to 0.48). Grade ≥3 treatment-related neutropenia occurred in 62.3% of patients on the triplet and 0.8% on the doublet, and grade ≥3 stomatitis in 19.2% and 12.3%; treatment-related discontinuation was 2.3% and 3.1%, and adverse-event rates for the fulvestrant arm were not reported.", "takeaway_ko": "CDK4/6 억제제와 아로마타제 억제제 치료 후 진행한 호르몬 수용체 양성, HER2 음성, PIK3CA 야생형 진행성 유방암 환자에서, 맹검 독립 중앙 판정에 의한 무진행 생존기간 중앙값은 게다톨리십·팔보시클립·풀베스트란트 3제 병용군에서 9.3개월, 풀베스트란트 단독군에서 2.0개월이었습니다(위험비 0.24, 95% 신뢰구간 0.17–0.35). 게다톨리십·풀베스트란트 2제 병용군에서는 7.4개월이었습니다(위험비 0.33, 95% 신뢰구간 0.24–0.48). 3도 이상 치료 관련 호중구감소증은 3제군 62.3%, 2제군 0.8%였고, 3도 이상 구내염은 각각 19.2%와 12.3%였습니다. 치료 관련 이상반응으로 인한 투약 중단은 각각 2.3%와 3.1%였으며, 풀베스트란트 단독군의 이상반응 발생률은 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-VERITAC2", "trial": "B-VERITAC2", "papers": [ { "key": "P-VERITAC2", "pmid": "40454645", "title": "Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454645/", "doi": "10.1056/NEJMoa2505725", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "VERITAC-2", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "After CDK4/6 inhibitor, advanced", "population": "ER+, HER2− advanced breast cancer", "claim": "Vepdegestrant (PROTAC ER degrader) vs fulvestrant: PFS 5.0 vs 2.1 months with ESR1 mutation (HR 0.58); 3.8 vs 3.6 months in all patients (HR 0.83, 0.69–1.01).", "trialRecord": { "key": "B-VERITAC2", "nct": "NCT05654623", "acronym": "VERITAC-2", "title": "A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 624, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [ "Arvinas Estrogen Receptor, Inc." ], "hasResults": true, "start": "2023-03-03", "lastUpdate": "2026-03-18", "url": "https://clinicaltrials.gov/study/NCT05654623" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by blinded independent central review among patients with ESR1 mutations and among all randomized patients", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 624, "assessment": "blinded independent central review", "quote": "In this phase 3, open-label, randomized trial … The primary end point was progression-free survival as assessed by blinded independent central review among the patients with ESR1 mutations and among all the patients who underwent randomization … A total of 624 patients underwent randomization; 313 were assigned to receive vepdegestrant, and 311 to receive fulvestrant." }, "effect": { "measure": "HR", "value": 0.58, "ci_low": 0.43, "ci_high": 0.78, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival in patients with ESR1 mutations (BICR)", "quote": "Among the 270 patients with ESR1 mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P<0.001). Among all the patients, the median progression-free survival was 3.8 months (95% CI, 3.7 to 5.3) with vepdegestrant and 3.6 months (95% CI, 2.6 to 4.0) with fulvestrant (hazard ratio, 0.83 [95% CI, 0.69 to 1.01]; P = 0.07)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 23.4, "grade3plus_control_pct": 17.6, "discontinuation_experimental_pct": 2.9, "discontinuation_control_pct": 0.7, "treatment_related_deaths": null, "quote": "Adverse events of grade 3 or higher occurred in 23.4% of the patients in the vepdegestrant group and in 17.6% of the patients in the fulvestrant group. Adverse events led to treatment discontinuation in 2.9% and 0.7% of the patients, respectively." }, "takeaway_en": "In ER-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor, oral vepdegestrant was compared with fulvestrant. In the 270 patients with ESR1 mutations, median progression-free survival was 5.0 versus 2.1 months (HR 0.58), but in all patients it was 3.8 versus 3.6 months (HR 0.83, 95% CI 0.69 to 1.01; P = 0.07), which was not significant. Grade 3 or higher adverse events occurred in 23.4% versus 17.6% of patients, and discontinuation due to adverse events in 2.9% versus 0.7%.", "takeaway_ko": "CDK4/6 억제제 치료 후 진행한 ER 양성, HER2 음성 진행성 유방암 환자에서 경구 베프데게스트란트와 풀베스트란트를 비교했습니다. ESR1 변이 환자 270명에서는 무진행생존기간 중앙값이 5.0개월 대 2.1개월(위험비 0.58)이었습니다. 전체 환자에서는 3.8개월 대 3.6개월(위험비 0.83, 95% 신뢰구간 0.69~1.01, P = 0.07)로 유의한 차이가 없었습니다. 3등급 이상 이상반응은 23.4% 대 17.6%, 이상반응으로 인한 치료 중단은 2.9% 대 0.7%로 베프데게스트란트군에서 더 많았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TROPiCS02", "trial": "B-TROPiCS02", "papers": [ { "key": "P-TROPiCS02", "pmid": "37633306", "title": "Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial.", "journal": "Lancet", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37633306/", "doi": "10.1016/S0140-6736(23)01245-X", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [ "BM-TROP2" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "TROPiCS-02", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Pretreated, metastatic", "population": "HR+, HER2− metastatic breast cancer", "claim": "Sacituzumab govitecan vs chemotherapy: OS 14.4 vs 11.2 months (HR 0.79); survival benefit was consistent across Trop-2 expression-level subgroups.", "trialRecord": { "key": "B-TROPiCS02", "nct": "NCT03901339", "acronym": "TROPiCS-02", "title": "Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 543, "sponsor": "Gilead Sciences", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2019-05-08", "lastUpdate": "2024-10-21", "url": "https://clinicaltrials.gov/study/NCT03901339" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (previously reported and not included in this analysis); this paper reports the protocol-specified final analysis of overall survival, a secondary endpoint", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 543, "assessment": "not stated", "quote": "In this randomised, open-label, multicentre, phase 3 trial … 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group." }, "effect": { "measure": "HR", "value": 0.79, "ci_low": 0.65, "ci_high": 0.96, "ci_level": "95%", "p": "0.020", "endpoint": "Overall survival (secondary endpoint, final analysis)", "quote": "Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0-15·7] vs 11·2 months [10·1-12·7]; hazard ratio [HR] 0·79, 95% CI 0·65-0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups." }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "Final analysis, data cutoff July 1, 2022 (12.5-month median follow-up)", "experimental_pct": 21, "control_pct": 14, "higher_is_better": true, "experimental_arm": "Sacituzumab govitecan", "control_arm": "Chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine)", "quote": "ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03-2·56]; p=0·035)", "difference_pp": 7, "nnt": 15, "quote_note": "from the 2023 Lancet final overall survival analysis, data cutoff July 1, 2022" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "One fatal adverse event (septic shock caused by neutropenic colitis) related to sacituzumab govitecan", "quote": "The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment." }, "takeaway_en": "In patients with pretreated, endocrine-resistant HR+/HER2− metastatic breast cancer (prior endocrine therapy, a taxane, a CDK4/6 inhibitor, and two to four chemotherapy regimens for metastatic disease), sacituzumab govitecan was compared with physician's-choice chemotherapy. It improved objective response rate (21% vs 14%) and median overall survival (14.4 vs 11.2 months; HR 0.79), with benefit consistent across Trop-2 expression subgroups. The abstract does not report rates of grade 3 or higher adverse events; one treatment-related death from septic shock due to neutropenic colitis occurred with sacituzumab govitecan.", "takeaway_ko": "이전 치료를 받은 내분비요법 저항성 HR 양성/HER2 음성 전이성 유방암 환자(내분비요법, 탁산, CDK4/6 억제제, 전이성 병기에서 2~4개의 항암화학요법 치료력)를 대상으로 사시투주맙 고비테칸과 의사 선택 항암화학요법을 비교했습니다. 사시투주맙 고비테칸군에서 객관적 반응률(21% 대 14%)과 전체생존기간 중앙값(14.4개월 대 11.2개월; 위험비 0.79)이 개선되었고, 이 이득은 Trop-2 발현 수준과 관계없이 일관되었습니다. 초록에는 3등급 이상 이상반응 발생률이 보고되지 않았으며, 사시투주맙 고비테칸군에서 호중구감소성 대장염에 의한 패혈성 쇼크로 치료 관련 사망 1건이 발생했습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TROPIONB01", "trial": "B-TROPIONB01", "papers": [ { "key": "P-TROPIONB01", "pmid": "39265124", "title": "Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39265124/", "doi": "10.1200/JCO.24.00920", "errata": [] }, { "key": "P-TROPIONB01OS", "pmid": "41448362", "title": "Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive, HER2-negative breast cancer: final overall survival analysis of the phase III TROPION-Breast01 study.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41448362/", "doi": "10.1016/j.annonc.2025.12.017", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "PFS and OS were separate primary endpoints; the earlier immature OS trend is superseded by the final analysis. Subsequent ADC use differed between arms (12.3% vs 24.0%), which may affect interpretation but does not establish a hidden survival benefit. The primary report recorded grade >=3 treatment-related adverse events in 20.8% vs 44.7%, with nausea and stomatitis prominent with datopotamab deruxtecan. The final abstract reported no new safety signal; this does not mean no treatment harms. Open-label design; the findings concern this selected treatment setting.", "label": "TROPION-Breast01", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Previously treated, inoperable or metastatic disease; randomized comparison of datopotamab deruxtecan with investigator-selected chemotherapy", "population": "HR-positive, HER2-negative breast cancer progressing on endocrine therapy, unsuitable for further endocrine therapy, after one or two chemotherapy lines for advanced disease", "claim": "The primary analysis showed improved centrally reviewed PFS with datopotamab deruxtecan (HR 0.63, 95% CI 0.52-0.76). At the final OS analysis, after a median follow-up of 22.8 months, OS was not significantly improved (HR 1.01, 95% CI 0.83-1.22; P=0.9445).", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-TROPIONB01", "nct": "NCT05104866", "acronym": null, "title": "A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 732, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo" ], "hasResults": true, "start": "2021-10-18", "lastUpdate": "2026-08-24", "url": "https://clinicaltrials.gov/study/NCT05104866" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Dual primary endpoints: progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "blinded independent central review", "quote": "The global, phase 3, open-label, randomized TROPION-Breast01 study … Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). … Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367)." }, "effect": { "measure": "HR", "value": 0.63, "ci_low": 0.52, "ci_high": 0.76, "ci_level": "95%", "p": "<.0001", "endpoint": "PFS by BICR (primary analysis); final OS analysis was not significant", "quote": "Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). … At data cut-off, median follow-up was 22.8 months. OS for the Dato-DXd versus ICC arm did not reach statistical significance (hazard ratio 1.01, 95% confidence interval 0.83-1.22, P = 0.9445).", "quote_note": "Final OS analysis, Ann Oncol 2026" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 20.8, "grade3plus_control_pct": 44.7, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC." }, "takeaway_en": "In patients with inoperable or metastatic HR-positive, HER2-negative breast cancer previously treated with endocrine therapy and one to two chemotherapy lines, datopotamab deruxtecan improved centrally reviewed progression-free survival versus investigator's choice of chemotherapy (HR 0.63, 95% CI 0.52-0.76). However, overall survival was not improved at the final analysis (HR 1.01, 95% CI 0.83-1.22), and subsequent ADC use was imbalanced (12.3% vs 24.0%); grade ≥3 treatment-related adverse events were less frequent with datopotamab deruxtecan (20.8% vs 44.7%), with nausea and stomatitis the most common side effects.", "takeaway_ko": "내분비요법 후 진행하고 진행성 병기에서 1~2차례 항암화학요법을 받은 수술 불가능 또는 전이성 호르몬수용체 양성, HER2 음성 유방암 환자에서, 다토포타맙 데룩스테칸은 연구자 선택 항암화학요법에 비해 맹검 독립 중앙 판정 무진행생존기간을 개선했습니다(HR 0.63, 95% CI 0.52-0.76). 그러나 최종 분석에서 전체생존기간은 개선되지 않았고(HR 1.01, 95% CI 0.83-1.22), 후속 항체-약물 접합체(ADC) 사용률은 군 간 불균형이 있었습니다(12.3% 대 24.0%). 3등급 이상 치료 관련 이상반응은 다토포타맙 데룩스테칸군에서 더 적었으며(20.8% 대 44.7%), 가장 흔한 이상반응은 오심과 구내염이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-Razavi18", "trial": null, "papers": [ { "key": "P-Razavi18", "pmid": "30205045", "title": "The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers.", "journal": "Cancer Cell", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30205045/", "doi": "10.1016/j.ccell.2018.08.008", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "Endocrine-resistant genomic landscape", "program": "breast", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "1,918 breast cancers (1,501 HR-positive) sequenced at MSK", "claim": "In 692 tumours previously exposed to hormonal therapy, alterations in MAPK pathway genes and in the ER transcriptional machinery were more frequent; they were present in 22% of tumours, were mutually exclusive with ESR1 mutations, and were associated with shorter responses to subsequent hormonal therapy.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-Fanning16", "trial": null, "papers": [ { "key": "P-Fanning16", "pmid": "26836308", "title": "Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation.", "journal": "Elife", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26836308/", "doi": "10.7554/eLife.12792", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "", "label": "ESR1 Y537S/D538G mechanism", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "population": "Structural, biophysical and cell-based studies", "claim": "ESR1 somatic mutations Y537S and D538G confer endocrine resistance by stabilising the activating function-2 (AF-2) binding conformation of ERα.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-KN522", "trial": "B-KN522", "papers": [ { "key": "P-KN522", "pmid": "32101663", "title": "Pembrolizumab for Early Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32101663/", "doi": "10.1056/NEJMoa1910549", "errata": [] }, { "key": "P-KN522EFS", "pmid": "35139274", "title": "Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35139274/", "doi": "10.1056/NEJMoa2112651", "errata": [] }, { "key": "P-KN522OS", "pmid": "39282906", "title": "Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39282906/", "doi": "10.1056/NEJMoa2409932", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "The randomized comparison tests the complete neoadjuvant/adjuvant strategy and cannot isolate the contribution of either treatment phase. pCR and EFS were primary endpoints; OS was secondary. Response is not synonymous with cure. The initial report recorded grade >=3 treatment-related adverse events across treatment phases in 78.0% vs 73.0%, including treatment-related deaths in 0.4% vs 0.3%; later abstracts described a consistent safety profile. These results do not establish benefit in metastatic disease or every early-stage subgroup. The registry first posted results on 2026-10-22 and includes later protocol-specified EFS and OS updates after earlier interim success; it explicitly labels the updated p-values nominal, without new formal statistical testing. The published time points retained in this claim are not the later registry update. Registry pCR subsets and response definitions differ from the initial publication, unreached survival medians are not zero, and overlapping phase-specific safety groups must not be summed as distinct patients. The new posting is the same trial, not an independent replication. The complete later report and statistical analysis plan were not received in this run.", "label": "KEYNOTE-522", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Neoadjuvant chemotherapy with pembrolizumab or placebo, followed after surgery by adjuvant pembrolizumab or placebo", "population": "Previously untreated stage II or III triple-negative breast cancer", "claim": "The first interim report found pCR in 64.8% vs 51.2% of the first 602 randomized patients. The later EFS analysis reported 36-month EFS of 84.5% vs 76.8% (HR 0.63, 95% CI 0.48-0.82). At the final OS analysis, median follow-up was 75.1 months and 60-month OS was 86.6% vs 81.7% (P=0.002).", "updated": "2026-10-23", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-KN522", "nct": "NCT03036488", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1174, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2017-03-07", "lastUpdate": "2026-10-22", "url": "https://clinicaltrials.gov/study/NCT03036488" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathological complete response (no invasive cancer in the breast and negative nodes) at definitive surgery and event-free survival in the intention-to-treat population (dual primary end points); overall survival was a secondary end point", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 1174, "assessment": "not stated", "quote": "In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer … Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group." }, "effect": { "measure": "HR", "value": 0.63, "ci_low": 0.48, "ci_high": 0.82, "ci_level": "95%", "p": "P<0.001", "endpoint": "Event-free survival (fourth planned interim analysis, median follow-up 39.1 months)", "quote": "The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001)." }, "landmark": [ { "endpoint": "Pathological complete response", "timepoint": "At definitive surgery (first interim analysis, first 602 randomized patients)", "experimental_pct": 64.8, "control_pct": 51.2, "higher_is_better": true, "experimental_arm": "Pembrolizumab + chemotherapy", "control_arm": "Placebo + chemotherapy", "quote": "among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001).", "difference_pp": 13.6, "nnt": 8, "quote_note": "P-KN522 (2020), first interim analysis" }, { "endpoint": "Event-free survival", "timepoint": "36 months", "experimental_pct": 84.5, "control_pct": 76.8, "higher_is_better": true, "experimental_arm": "Pembrolizumab + chemotherapy", "control_arm": "Placebo + chemotherapy", "quote": "The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group.", "difference_pp": 7.7, "nnt": 13, "quote_note": "P-KN522EFS (2022), fourth planned interim analysis, median follow-up 39.1 months" }, { "endpoint": "Overall survival", "timepoint": "60 months", "experimental_pct": 86.6, "control_pct": 81.7, "higher_is_better": true, "experimental_arm": "Pembrolizumab + chemotherapy", "control_arm": "Placebo + chemotherapy", "quote": "The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002).", "difference_pp": 4.9, "nnt": 21, "quote_note": "P-KN522OS (2024), final OS analysis, median follow-up 75.1 months" } ], "harms": { "grade3plus_experimental_pct": 78, "grade3plus_control_pct": 73, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "0.4% (3 patients) with pembrolizumab-chemotherapy vs 0.3% (1 patient) with placebo-chemotherapy (first report, 2020)", "quote": "Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively." }, "takeaway_en": "In previously untreated stage II or III triple-negative breast cancer, adding neoadjuvant and adjuvant pembrolizumab to platinum-containing chemotherapy raised pathological complete response from 51.2% to 64.8% (13.6 percentage points). It also raised 36-month event-free survival from 76.8% to 84.5% (HR 0.63) and 60-month overall survival from 81.7% to 86.6%, at the cost of more grade 3 or higher treatment-related adverse events (78.0% vs 73.0%) and 3 vs 1 treatment-related deaths.", "takeaway_ko": "이전 치료력이 없는 2-3기 삼중음성 유방암 환자에서 백금 포함 항암화학요법에 수술 전후 펨브롤리주맙을 추가하자 병리학적 완전관해율이 51.2%에서 64.8%로 13.6%p 높아졌습니다. 36개월 무사건생존율은 76.8%에서 84.5%로(위험비 0.63), 60개월 전체생존율은 81.7%에서 86.6%로 개선되었으나, 3등급 이상 치료 관련 이상반응은 78.0% 대 73.0%로 더 많았고 치료 관련 사망은 3명 대 1명이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-IMP130", "trial": "B-IMP130", "papers": [ { "key": "P-IMP130", "pmid": "30345906", "title": "Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30345906/", "doi": "10.1056/NEJMoa1809615", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [ "BM-PDL1-B" ], "subtypes": [ "B-TNBC" ], "limits": "", "label": "IMpassion130", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, advanced", "population": "Advanced triple-negative breast cancer", "claim": "Atezolizumab plus nab-paclitaxel: ITT PFS 7.2 vs 5.5 months (HR 0.80).", "trialRecord": { "key": "B-IMP130", "nct": "NCT02425891", "acronym": null, "title": "A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 902, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-06-23", "lastUpdate": "2022-07-19", "url": "https://clinicaltrials.gov/study/NCT02425891" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (ITT population and PD-L1-positive subgroup) and overall survival (ITT, then PD-L1-positive subgroup if significant); two co-primary end points", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel … Each group included 451 patients (median follow-up, 12.9 months)." }, "effect": { "measure": "HR", "value": 0.8, "ci_low": 0.69, "ci_high": 0.92, "ci_level": "95%", "p": "P=0.002", "endpoint": "Progression-free survival, intention-to-treat population", "quote": "In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P=0.002)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 15.9, "discontinuation_control_pct": 8.2, "treatment_related_deaths": null, "quote": "No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel." }, "takeaway_en": "In untreated metastatic triple-negative breast cancer, adding atezolizumab to nab-paclitaxel improved progression-free survival compared with placebo plus nab-paclitaxel in the intention-to-treat population (median 7.2 vs 5.5 months; HR 0.80, 95% CI 0.69 to 0.92), but the overall survival difference was not significant in that population (HR 0.84, P=0.08). Adverse events leading to discontinuation of any agent occurred in 15.9% with atezolizumab versus 8.2% with placebo, and no new adverse effects were identified.", "takeaway_ko": "치료받지 않은 전이성 삼중음성 유방암 환자에서 nab-paclitaxel에 atezolizumab을 추가하면, 위약과 nab-paclitaxel 병용에 비해 전체 환자군(ITT)의 무진행생존기간이 개선되었으나(중앙값 7.2개월 대 5.5개월; HR 0.80, 95% CI 0.69–0.92), 같은 환자군에서 전체생존기간 차이는 통계적으로 유의하지 않았습니다(HR 0.84, P=0.08). 이상반응으로 약제를 중단한 비율은 atezolizumab군 15.9%, 위약군 8.2%였으며, 새로운 이상반응은 확인되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-IMP131", "trial": "B-IMP131", "papers": [ { "key": "P-IMP131", "pmid": "34219000", "title": "Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer.", "journal": "Ann Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34219000/", "doi": "10.1016/j.annonc.2021.05.801", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [ "BM-PDL1-B" ], "subtypes": [ "B-TNBC" ], "limits": "", "label": "IMpassion131", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "First line, advanced", "population": "Advanced triple-negative breast cancer (45% PD-L1-positive)", "claim": "Atezolizumab plus paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population (HR 0.82, 0.60–1.12; P = 0.20).", "trialRecord": { "key": "B-IMP131", "nct": "NCT03125902", "acronym": "IMpassion131", "title": "A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 653, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2017-08-25", "lastUpdate": "2024-03-26", "url": "https://clinicaltrials.gov/study/NCT03125902" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS), tested hierarchically first in the PD-L1-positive population (immune cell expression ≥1%, VENTANA SP142) and then in the ITT population", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 651, "assessment": "investigator", "quote": "Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial … Of 651 randomised patients, 45% had PD-L1-positive aTNBC … The primary endpoint was investigator-assessed PFS" }, "effect": { "measure": "HR", "value": 0.82, "ci_low": 0.6, "ci_high": 1.12, "ci_level": "95%", "p": "0.20", "endpoint": "Investigator-assessed PFS, PD-L1-positive population", "quote": "adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]" }, "landmark": [ { "endpoint": "Unconfirmed best overall response rate (PD-L1-positive population)", "timepoint": "best overall response (no fixed time point)", "experimental_pct": 63, "control_pct": 55, "higher_is_better": true, "experimental_arm": "Atezolizumab + paclitaxel", "control_arm": "Placebo + paclitaxel", "quote": "In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel)", "difference_pp": 8, "nnt": 13, "quote_note": "primary results paper, Ann Oncol 2021, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The safety profile was consistent with known effects of each study drug." }, "takeaway_en": "In first-line unresectable locally advanced or metastatic triple-negative breast cancer, adding atezolizumab to weekly paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population (HR 0.82, 95% CI 0.60-1.12; median 6.0 vs 5.7 months), and final OS showed no difference (HR 1.11, 95% CI 0.76-1.64; median 22.1 vs 28.3 months), although the unconfirmed response rate was 63% versus 55%. The abstract reports no harm rates and states only that the safety profile was consistent with the known effects of each drug.", "takeaway_ko": "절제 불가능한 국소 진행성 또는 전이성 삼중음성 유방암의 1차 치료에서, 주간 파클리탁셀에 아테졸리주맙을 추가해도 PD-L1 양성군의 연구자 평가 무진행생존기간은 개선되지 않았습니다(위험비 0.82, 95% 신뢰구간 0.60-1.12; 중앙값 6.0개월 대 5.7개월). 최종 전체생존기간도 차이가 없었으며(위험비 1.11, 95% 신뢰구간 0.76-1.64; 중앙값 22.1개월 대 28.3개월), 확인되지 않은 반응률은 63% 대 55%였습니다. 초록에는 이상반응 발생률이 보고되지 않았고, 안전성 프로파일은 각 약제의 알려진 효과와 일치한다고만 기술되어 있습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ASCENT", "trial": "B-ASCENT", "papers": [ { "key": "P-ASCENT", "pmid": "33882206", "title": "Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33882206/", "doi": "10.1056/NEJMoa2028485", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "", "label": "ASCENT", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Refractory or relapsed, metastatic", "population": "Metastatic triple-negative breast cancer", "claim": "Sacituzumab govitecan (Trop-2 antibody coupled to SN-38, a topoisomerase I inhibitor) vs chemotherapy: PFS 5.6 vs 1.7 months (HR 0.41); OS 12.1 vs 6.7 months (HR 0.48).", "trialRecord": { "key": "B-ASCENT", "nct": "NCT02574455", "acronym": "ASCENT", "title": "Trial of Sacituzumab Govitecan in Participants With Refractory/Relapsed Metastatic Triple-Negative Breast Cancer (TNBC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 529, "sponsor": "Gilead Sciences", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2017-11-07", "lastUpdate": "2022-06-15", "url": "https://clinicaltrials.gov/study/NCT02574455" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (by blinded independent central review) among patients without brain metastases", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 468, "assessment": "blinded independent central review", "quote": "In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. … A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients)." }, "effect": { "measure": "HR", "value": 0.41, "ci_low": 0.32, "ci_high": 0.52, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001)." }, "landmark": [ { "endpoint": "Objective response", "timepoint": "Best response during study (no time point stated)", "experimental_pct": 35, "control_pct": 5, "higher_is_better": true, "experimental_arm": "Sacituzumab govitecan", "control_arm": "Physician's-choice single-agent chemotherapy", "quote": "The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy.", "difference_pp": 30, "nnt": 4, "quote_note": "P-ASCENT, N Engl J Med 2021, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Three deaths due to adverse events in each group; none considered related to sacituzumab govitecan", "quote": "The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment." }, "takeaway_en": "In 468 patients with relapsed or refractory metastatic triple-negative breast cancer without brain metastases, all previously treated with taxanes, sacituzumab govitecan was compared with physician's-choice single-agent chemotherapy. Objective response was 35% vs 5%, median progression-free survival was 5.6 vs 1.7 months (HR 0.41), and median overall survival was 12.1 vs 6.7 months (HR 0.48). The trade-off was more grade 3 or higher neutropenia (51% vs 33%) and diarrhea (10% vs <1%).", "takeaway_ko": "탁산 치료 경험이 있고 뇌전이가 없는 재발성 또는 불응성 전이성 삼중음성 유방암 환자 468명을 대상으로 사시투주맙 고비테칸과 의사 선택 단일 항암화학요법을 비교했습니다. 객관적 반응률은 35% 대 5%였고, 무진행생존기간 중앙값은 5.6개월 대 1.7개월(위험비 0.41), 전체생존기간 중앙값은 12.1개월 대 6.7개월(위험비 0.48)이었습니다. 대신 3등급 이상 호중구감소증(51% 대 33%)과 설사(10% 대 <1%)가 더 많았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-OlympiA", "trial": "B-OlympiA", "papers": [ { "key": "P-OlympiA", "pmid": "34081848", "title": "Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.", "journal": "N Engl J Med", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34081848/", "doi": "10.1056/NEJMoa2105215", "errata": [] }, { "key": "P-OlympiAOS", "pmid": "36228963", "title": "Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.", "journal": "Ann Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36228963/", "doi": "10.1016/j.annonc.2022.09.159", "errata": [] }, { "key": "P-OlympiA6y", "pmid": "42636977", "title": "Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: updated results from the OlympiA phase III trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42636977/", "doi": "10.1016/j.annonc.2026.08.002", "errata": [] } ], "pages": [], "targets": [ "PARP1" ], "biomarkers": [ "BM-gBRCA" ], "subtypes": [], "limits": "Population is restricted to germline BRCA1/2 pathogenic or likely pathogenic variants with high-risk, HER2-negative early breast cancer following definitive local therapy and (neo)adjuvant chemotherapy; findings do not apply to all BRCA-mutated malignancies. Efficacy is anchored by primary endpoint IDFS. While OS reached formal statistical significance at the prespecified second interim analysis (P=0.009 < 0.015), the 6.1-year third interim analysis provides descriptive updates rather than a new confirmatory hypothesis test. Regarding harms, while adverse events of special interest and MDS/AML incidences were not elevated with olaparib (MDS/AML 0.4% vs 0.7%), the absence of an observed increase does not prove the absence of long-term safety issues or negate established PARP inhibitor toxicities.", "label": "OlympiA", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant", "population": "Germline BRCA1/2-mutated, HER2-negative early breast cancer", "claim": "In high-risk, HER2-negative early breast cancer with germline BRCA1/2 pathogenic variants, 1 year of adjuvant olaparib significantly improved 3-year IDFS over placebo (85.9% vs 77.1%; HR 0.58, 99.5% CI 0.41–0.82; P<0.001). At a median follow-up of 3.5 years, OS formally met the prespecified boundary for the second interim analysis (HR 0.68, 98.5% CI 0.47–0.97; P=0.009; 4-year OS 89.8% vs 86.4%). At a median follow-up of 6.1 years, descriptive analyses reported sustained benefit in IDFS (HR 0.65, 95% CI 0.53–0.78) and OS (HR 0.72, 95% CI 0.56–0.93; 6-year OS 87.5% vs 83.2%).", "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8; reviewed by Muse Spark1.3; integrated by Codex (GPT-6)", "trialRecord": { "key": "B-OlympiA", "nct": "NCT02032823", "acronym": "OlympiA", "title": "Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 1837, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Frontier Science & Technology Research Foundation, Inc.", "NRG Oncology", "Myriad Genetic Laboratories, Inc.", "The Breast Adjuvant Study Team", "Merck Sharp & Dohme LLC" ], "hasResults": true, "start": "2014-04-22", "lastUpdate": "2026-07-14", "url": "https://clinicaltrials.gov/study/NCT02032823" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (IDFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 1836, "assessment": "not stated", "quote": "We conducted a phase 3, double-blind, randomized trial … Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. … A total of 1836 patients underwent randomization." }, "effect": { "measure": "HR", "value": 0.58, "ci_low": 0.41, "ci_high": 0.82, "ci_level": "99.5%", "p": "<0.001", "endpoint": "Invasive disease-free survival (primary, prespecified interim analysis, median follow-up 2.5 years; 99.5% CI)", "quote": "hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001" }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "4 years", "experimental_pct": 82.7, "control_pct": 75.4, "higher_is_better": true, "experimental_arm": "Olaparib", "control_arm": "Placebo", "quote": "Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%)", "difference_pp": 7.3, "nnt": 14, "quote_note": "Ann Oncol 2022, median follow-up 3.5 years; most recent IDFS landmark reported; the 6.1-year update reports IDFS only as HR" }, { "endpoint": "Distant disease-free survival", "timepoint": "4 years", "experimental_pct": 86.5, "control_pct": 79.1, "higher_is_better": true, "experimental_arm": "Olaparib", "control_arm": "Placebo", "quote": "4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively", "difference_pp": 7.4, "nnt": 14, "quote_note": "Ann Oncol 2022, median follow-up 3.5 years; most recent DDFS landmark reported" }, { "endpoint": "Overall survival", "timepoint": "6 years", "experimental_pct": 87.5, "control_pct": 83.2, "higher_is_better": true, "experimental_arm": "Olaparib", "control_arm": "Placebo", "quote": "The 6-year OS for olaparib versus placebo was 87.5% versus 83.2% (difference 4.4%, 95% CI 0.9% to 6.7%).", "difference_pp": 4.3, "nnt": 24, "quote_note": "Ann Oncol 2026, median follow-up 6.1 years; most recent paper" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. … there was no increase in AESI risks (6.3% versus 9.3%), including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) (0.4% versus 0.7%), with olaparib versus placebo." }, "takeaway_en": "In 1836 patients with germline BRCA1/2-mutated, high-risk, HER2-negative early breast cancer, 1 year of adjuvant olaparib after chemotherapy was compared with placebo. Four-year invasive disease-free survival was 82.7% vs 75.4%, and 6-year overall survival was 87.5% vs 83.2% (difference 4.4%). The abstracts do not report grade 3 or higher adverse event rates. They state there were no excess serious adverse events and no increase in adverse events of special interest (6.3% vs 9.3%), including MDS/AML (0.4% vs 0.7%).", "takeaway_ko": "생식세포 BRCA1/2 변이가 있는 고위험 HER2 음성 조기 유방암 환자 1836명을 대상으로, 항암화학요법 후 1년간의 보조 올라파립을 위약과 비교했습니다. 4년 침습적 무질병 생존율은 82.7% 대 75.4%였고, 6년 전체 생존율은 87.5% 대 83.2%(차이 4.4%)였습니다. 초록에는 3등급 이상 이상반응 발생률이 보고되지 않았습니다. 다만 중대한 이상반응의 증가는 없었고, 특별 관심 이상반응도 증가하지 않았다고 기술되어 있습니다(6.3% 대 9.3%, 골수형성이상증후군/급성골수성백혈병 0.4% 대 0.7%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TCGABRCA", "trial": null, "papers": [ { "key": "P-TCGABRCA", "pmid": "23000897", "title": "Comprehensive molecular portraits of human breast tumours.", "journal": "Nature", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/23000897/", "doi": "10.1038/nature11412", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "TCGA breast", "program": "breast", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "Primary breast tumours", "claim": "Comprehensive molecular portraits of human breast tumours (TCGA, 2012).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-METABRIC", "trial": null, "papers": [ { "key": "P-METABRIC", "pmid": "22522925", "title": "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.", "journal": "Nature", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22522925/", "doi": "10.1038/nature10983", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "METABRIC", "program": "breast", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "~2,000 primary breast tumours", "claim": "Genomic and transcriptomic architecture of 2,000 breast tumours revealing novel subgroups (2012).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CPTACBRCA", "trial": null, "papers": [ { "key": "P-CPTACBRCA", "pmid": "33212010", "title": "Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy.", "journal": "Cell", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33212010/", "doi": "10.1016/j.cell.2020.10.036", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "CPTAC breast proteogenomics", "program": "breast", "kind": "genomics", "level": "computational", "result": "descriptive", "population": "Breast tumours", "claim": "Proteogenomic landscape of breast cancer tumorigenesis and targeted therapy (CPTAC, 2020).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AF2", "trial": null, "papers": [ { "key": "P-AF2", "pmid": "34265844", "title": "Highly accurate protein structure prediction with AlphaFold.", "journal": "Nature", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34265844/", "doi": "10.1038/s41586-021-03819-2", "errata": [] } ], "pages": [ { "key": "af2-readme", "title": "google-deepmind/alphafold — README (Model parameters)", "url": "https://github.com/google-deepmind/alphafold/blob/main/README.md", "file": "data/sources/pages/af2-readme.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "AlphaFold 2", "program": "method", "kind": "method", "level": "literature", "result": "descriptive", "claim": "Protein structure prediction method (Nature 2021). Code Apache 2.0; parameters CC BY 4.0 (README saved 2026-09-28).", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-AFDB", "trial": null, "papers": [ { "key": "P-AFDB22", "pmid": "34791371", "title": "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models.", "journal": "Nucleic Acids Res", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/34791371/", "doi": "10.1093/nar/gkab1061", "errata": [] }, { "key": "P-AFDB24", "pmid": "37933859", "title": "AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences.", "journal": "Nucleic Acids Res", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37933859/", "doi": "10.1093/nar/gkad1011", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "AlphaFold Protein Structure Database", "program": "method", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "Database of AlphaFold predictions run by EMBL-EBI with Google DeepMind (NAR 2022; 2024 update: over 214 million entries).", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-AF3", "trial": null, "papers": [ { "key": "P-AF3", "pmid": "38718835", "title": "Accurate structure prediction of biomolecular interactions with AlphaFold 3.", "journal": "Nature", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38718835/", "doi": "10.1038/s41586-024-07487-w", "errata": [] } ], "pages": [ { "key": "af3-readme", "title": "google-deepmind/alphafold3 — README (Licence and Disclaimer)", "url": "https://github.com/google-deepmind/alphafold3/blob/main/README.md", "file": "data/sources/pages/af3-readme.txt" }, { "key": "af3-weights-terms", "title": "google-deepmind/alphafold3 — Model Parameters Terms of Use", "url": "https://github.com/google-deepmind/alphafold3/blob/main/WEIGHTS_TERMS_OF_USE.md", "file": "data/sources/pages/af3-weights-terms.txt" }, { "key": "ebi-af3-struggles", "title": "EMBL-EBI — What AlphaFold 3 struggles with", "url": "https://www.ebi.ac.uk/training/online/courses/alphafold/alphafold-3-and-alphafold-server/introducing-alphafold-3/what-alphafold-3-struggles-with/", "file": "data/sources/pages/ebi-af3-struggles.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "AlphaFold 3", "program": "method", "kind": "method", "level": "literature", "result": "descriptive", "claim": "Biomolecular complex prediction (Nature 2024). Source code Apache 2.0; model parameters only for non-commercial use by or on behalf of non-commercial organisations (terms saved 2026-09-28).", "trialRecord": null, "sources": 4, "corrections": 0, "analysisRecord": null }, { "id": "U-AFServer", "trial": null, "papers": [], "pages": [ { "key": "ebi-af-server", "title": "EMBL-EBI — AlphaFold Server: your gateway to AlphaFold 3", "url": "https://www.ebi.ac.uk/training/online/courses/alphafold/alphafold-3-and-alphafold-server/alphafold-server-your-gateway-to-alphafold-3/", "file": "data/sources/pages/ebi-af-server.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "AlphaFold Server", "program": "method", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "Web service running AlphaFold 3. Non-commercial use only; outputs cannot be used in docking or screening tools or to train similar models; 5,000-token job limit; 30 jobs per user per day (EMBL-EBI guide saved 2026-09-28).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-RoseTTAFold", "trial": null, "papers": [ { "key": "P-RoseTTAFold", "pmid": "34282049", "title": "Accurate prediction of protein structures and interactions using a three-track neural network.", "journal": "Science", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34282049/", "doi": "10.1126/science.abj8754", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "RoseTTAFold", "program": "method", "kind": "method", "level": "literature", "result": "descriptive", "claim": "Three-track neural network for protein structures and interactions (Science 2021).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-RFdiffusion", "trial": null, "papers": [ { "key": "P-RFdiffusion", "pmid": "37433327", "title": "De novo design of protein structure and function with RFdiffusion.", "journal": "Nature", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37433327/", "doi": "10.1038/s41586-023-06415-8", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "RFdiffusion", "program": "method", "kind": "method", "level": "literature", "result": "descriptive", "claim": "De novo design of protein structure and function with RFdiffusion (Nature 2023).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2Fab", "trial": null, "papers": [ { "key": "P-HER2Fab", "pmid": "12610629", "title": "Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.", "journal": "Nature", "year": "2003", "url": "https://pubmed.ncbi.nlm.nih.gov/12610629/", "doi": "10.1038/nature01392", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "", "label": "HER2 ECD + trastuzumab Fab (1N8Z)", "program": "structure", "kind": "structure", "level": "preclinical", "result": "descriptive", "claim": "Crystal structures of the HER2 extracellular region alone and with the Herceptin Fab; 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each ligand class induces a distinct conformation of the transactivation domain.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ERtam", "trial": null, "papers": [ { "key": "P-ERtam", "pmid": "9875847", "title": "The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.", "journal": "Cell", "year": "1998", "url": "https://pubmed.ncbi.nlm.nih.gov/9875847/", "doi": "10.1016/s0092-8674(00)81717-1", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [], "subtypes": [], "limits": "", "label": "ERα LBD + 4-hydroxytamoxifen (3ERT)", "program": "structure", "kind": "structure", "level": "preclinical", "result": "descriptive", "claim": "Structural basis of ER/coactivator recognition and its antagonism by tamoxifen (Cell 1998).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-BYL719", "trial": null, "papers": [ { "key": "P-BYL719", "pmid": "23726034", "title": "Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation.", "journal": "Bioorg Med Chem Lett", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23726034/", "doi": "10.1016/j.bmcl.2013.05.007", "errata": [ { "pmid": null, "title": "Bioorg Med Chem Lett. 2013 Aug 15;23(16):4723", "url": "https://pubmed.ncbi.nlm.nih.gov/23726034/", "reviewed": false, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [ "PIK3CA" ], "biomarkers": [], "subtypes": [], "limits": "", "label": "Alpelisib discovery (4JPS)", "program": "structure", "kind": "structure", "level": "preclinical", "result": "descriptive", "claim": "A binding model for 2-aminothiazole PI3Kα inhibitors led to the clinical candidate NVP-BYL719 (alpelisib). 4JPS holds the p110α catalytic and p85α regulatory subunits.", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null }, { "id": "U-cBio", "trial": null, "papers": [ { "key": "P-cBio", "pmid": "22588877", "title": "The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.", "journal": "Cancer Discov", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22588877/", "doi": "10.1158/2159-8290.CD-12-0095", "errata": [ { "pmid": null, "title": "Cancer Discov. 2012 Oct;2(10):960", "url": "https://aacrjournals.org/cancerdiscovery/article/2/10/960/2824/Correction-The-cBio-Cancer-Genomics-Portal-An-Open", "reviewed": true, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "cBioPortal", "program": "data", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "Open platform for exploring multidimensional cancer genomics data (2012). IATHEON analyses A1 and A2 use its public API.", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null }, { "id": "U-GENIE", "trial": null, "papers": [ { "key": "P-GENIE", "pmid": "28572459", "title": "AACR Project GENIE: Powering Precision Medicine through an International Consortium.", "journal": "Cancer Discov", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28572459/", "doi": "10.1158/2159-8290.CD-17-0151", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "AACR Project GENIE", "program": "data", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "International clinico-genomic data-sharing consortium (2017).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-DepMap", "trial": null, "papers": [ { "key": "P-DepMap", "pmid": "28753430", "title": "Defining a Cancer Dependency Map.", "journal": "Cell", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28753430/", "doi": "10.1016/j.cell.2017.06.010", "errata": [] }, { "key": "P-CCLE19", "pmid": "31068700", "title": "Next-generation characterization of the Cancer Cell Line Encyclopedia.", "journal": "Nature", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31068700/", "doi": "10.1038/s41586-019-1186-3", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "Cancer Dependency Map", "program": "data", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "Genome-scale dependency screens (Cell 2017) and the Cancer Cell Line Encyclopedia characterisation (Nature 2019).", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-GDC", "trial": null, "papers": [ { "key": "P-GDC", "pmid": "27653561", "title": "Toward a Shared Vision for Cancer Genomic Data.", "journal": "N Engl J Med", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27653561/", "doi": "10.1056/NEJMp1607591", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "NCI Genomic Data Commons", "program": "data", "kind": "resource", "level": "literature", "result": "descriptive", "claim": "Shared infrastructure for cancer genomic data (NEJM 2016).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-NCI-BREAST", "trial": null, "papers": [], "pages": [ { "key": "nci-breast-targeted", "title": "NCI — Targeted Therapy for Breast Cancer", "url": "https://www.cancer.gov/types/breast/treatment/targeted-therapy", "file": "data/sources/pages/nci-breast-targeted.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "NCI: Targeted therapy for breast cancer", "program": "breast", "kind": "reference-page", "level": "literature", "result": "descriptive", "claim": "Lists targeted drugs by setting: HER2-positive (ado-trastuzumab, lapatinib, margetuximab, neratinib, pertuzumab, tucatinib, trastuzumab and co-formulations, trastuzumab deruxtecan also for HER2-low); HR-positive (abemaciclib, alpelisib, capivasertib, camizestrant, datopotamab, everolimus, gedatolisib, inavolisib, palbociclib, ribociclib, sacituzumab); TNBC (datopotamab, pembrolizumab, sacituzumab); BRCA-mutated (olaparib, talazoparib).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-NCI-PDQ", "trial": null, "papers": [], "pages": [ { "key": "nci-stomach-pdq-hp", "title": "NCI PDQ — Gastric Cancer Treatment (Health Professional)", "url": "https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq", "file": "data/sources/pages/nci-stomach-pdq-hp.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "", "label": "NCI PDQ: Stomach cancer treatment (HP)", "program": "gastric", "kind": "reference-page", "level": "literature", "result": "descriptive", "claim": "For stage IV, inoperable and recurrent disease, the page lists: nivolumab with chemotherapy; zolbetuximab with CAPOX or mFOLFOX6 for CLDN18.2-positive tumours; trastuzumab with chemotherapy; ramucirumab with or without chemotherapy; pembrolizumab for dMMR or MSI-H tumours; trastuzumab deruxtecan for HER2-positive tumours (IHC 3+ or IHC 2+/FISH+); trifluridine and tipiracil. It recommends testing HER2, dMMR/MSI and PD-L1 CPS in metastatic disease.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-A1", "trial": null, "papers": [], "pages": [], "targets": [ "ERBB2", "FGFR2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2", "B-HER2POS" ], "limits": "GISTIC calls on bulk primary tumours; not clinical HER2 status by IHC/ISH; no treatment or outcome data; GRB7 and CDK12 co-amplify because they share the 17q12 amplicon.", "label": "A1 · ERBB2 co-amplification, TCGA gastric vs breast", "program": "gxb", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A1", "population": "TCGA PanCancer Atlas: 438 gastric and 1,070 breast tumours with copy-number calls", "claim": "High-level ERBB2 amplification in 58/438 gastric (13.2%) and 123/1,070 breast (11.5%) tumours. Among ERBB2-amplified tumours, amplification of EGFR, MET, FGFR2, KRAS or CCNE1 occurred in 27/58 gastric (46.6%) vs 9/123 breast (7.3%); CCNE1 alone 31.0% vs 3.3%.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": { "id": "A1", "title": "ERBB2 amplification and co-amplification in TCGA gastric (STAD) and breast (BRCA) tumours", "retrieved": "2026-09-28", "method": "cBioPortal public API; GISTIC 2.0 discrete calls, value 2 = high-level amplification; denominator = samples with CNA data" } }, { "id": "U-A2", "trial": null, "papers": [], "pages": [], "targets": [ "ESR1", "PIK3CA" ], "biomarkers": [ "BM-ESR1", "BM-PI3K" ], "subtypes": [ "B-HRPOS" ], "limits": "Cross-sectional samples from different patients, not paired; prior therapy is not modelled; one institution; tumour sequencing panel, not ctDNA.", "label": "A2 · ESR1 and PIK3CA, primary vs metastatic", "program": "breast", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A2", "population": "MSK 2018 breast (Razavi et al.): 918 primary and 1,000 metastatic samples; TCGA PanCancer Atlas breast as reference", "claim": "In HR+/HER2− samples, ESR1 mutations in 121/629 metastatic (19.2%) vs 19/733 primary (2.6%); PIK3CA 41.2% vs 43.7%. Most frequent ESR1 changes in metastatic samples: D538G (51), Y537S (26), E380Q (12). TCGA luminal primaries: ESR1 8/696 (1.1%), PIK3CA 42.5%.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": { "id": "A2", "title": "ESR1 and PIK3CA mutations in primary and metastatic breast tumour samples (MSK-IMPACT, Razavi et al. 2018) with TCGA luminal primaries as reference", "retrieved": "2026-09-28", "method": "cBioPortal public API; non-synonymous mutations; one count per sample; groups by SAMPLE_TYPE, HR_STATUS and OVERALL_HER2_STATUS as recorded in the study" } }, { "id": "U-A3", "trial": null, "papers": [], "pages": [], "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "subtypes": [], "limits": "Sequence comparison only. Topology annotation is for the canonical isoform and is assumed, not shown, to hold for A2.", "label": "A3 · CLDN18 isoform comparison", "program": "gastric", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A3", "population": "UniProt P56856 isoforms A1 (P56856-1, canonical) and A2 (P56856-2, CLDN18.2)", "claim": "Both isoforms are 261 residues. They differ at 21 positions, all within residues 1–69 (UniProt: alternative sequence 1–69 in isoform A2); residues 70–261 are identical. By UniProt topology for the canonical sequence, residues 1–69 span the N-terminal cytoplasmic segment (1–6), the first transmembrane helix (7–27) and most of the first extracellular segment (28–80).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": { "id": "A3", "title": "CLDN18 isoform A1 (canonical) vs isoform A2 (CLDN18.2) sequence comparison", "retrieved": "2026-09-28", "method": "UniProt REST FASTA for both isoform accessions, position-by-position comparison; topology and alternative-sequence annotation read from the P56856 entry. The topology is annotated for the canonical isoform; whether it holds for A2 is not shown here." } }, { "id": "U-A5", "trial": null, "papers": [ { "key": "P-Razavi18", "pmid": "30205045", "title": "The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers.", "journal": "Cancer Cell", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30205045/", "doi": "10.1016/j.ccell.2018.08.008", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "Small, selected paired cohort; specimens were not always collected in primary-then-metastatic order. Detection, assay sensitivity and treatment history do not establish mutation acquisition, tumour evolution or treatment effects. The source paper describes the dataset; the new paired calculations are our own. The decoder correction for missing Entrez identifiers, made after the inputs were acquired, is disclosed in the analysis record.", "label": "A5 · Paired ESR1 detection in primary and metastatic breast specimens", "program": "breast", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A5", "population": "MSK breast cancer patients with one metadata-selected primary and metastatic tissue specimen; reuses the A2 source collection", "claim": "In the paired comparison, metastatic-only ESR1 detection was more frequent than primary-only detection. The exact paired inference, the complete detection table and the uncertainty estimates are given in the linked analysis report. This is an internal observational calculation, not an external cohort validation.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": { "id": "A5", "title": "Paired ESR1 detection in primary and metastatic breast specimens", "retrieved": "2026-09-30", "method": "One metadata-selected primary/metastatic pair per patient; non-synonymous ESR1 detection; exact two-sided McNemar test, exact discordant-direction interval and descriptive marginal Wilson intervals." } }, { "id": "U-DS8201pre16", "trial": null, "papers": [ { "key": "P-DS8201pre16", "pmid": "27026201", "title": "DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.", "journal": "Clin Cancer Res", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27026201/", "doi": "10.1158/1078-0432.CCR-15-2822", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "These are preclinical models, not patient efficacy or safety results. Model-specific activity does not establish optimal ADC sequencing. Experimental low HER2 expression must not be equated with later clinical HER2-low or ultralow scoring categories.", "label": "DS-8201a functional preclinical profile", "program": "gxb", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "HER2-directed ADC activity in cell and animal models", "population": "HER2-expressing cancer cell lines, a gastric cancer model, and breast cancer patient-derived xenografts", "claim": "DS-8201a inhibited cell growth in relation to HER2 expression and induced tumor regression in a HER2-positive gastric model. Activity was also reported in a T-DM1-insensitive xenograft with high HER2 expression and in breast cancer xenografts with low HER2 expression.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ZOLpre24", "trial": null, "papers": [ { "key": "P-ZOLpre24", "pmid": "38797537", "title": "Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models.", "journal": "J Pharmacol Sci", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38797537/", "doi": "10.1016/j.jphs.2024.04.004", "errata": [] } ], "pages": [], "targets": [ "CLDN18.2" ], "biomarkers": [], "subtypes": [], "limits": "Cell and mouse findings do not establish clinical combination benefit or human safety. The study does not compare the clinical CLDN18.2 assay thresholds used in different trials; model expression positivity does not establish that those thresholds select the same patients.", "label": "Zolbetuximab functional gastric models", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "CLDN18.2-directed antibody activity in gastric cancer models", "population": "CLDN18.2-positive human cancer cells and gastric cancer xenograft or syngeneic mouse models", "claim": "Zolbetuximab elicited antibody-dependent and complement-dependent killing of CLDN18.2-positive cells. Gastric mouse models showed tumor inhibition with antibody alone or with chemotherapy. Combining zolbetuximab with mouse PD-1 blockade produced stronger tumor suppression than either monotherapy.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AZD5363pre12", "trial": null, "papers": [ { "key": "P-AZD5363pre12", "pmid": "22294718", "title": "Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background.", "journal": "Mol Cancer Ther", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22294718/", "doi": "10.1158/1535-7163.MCT-11-0824-T", "errata": [] } ], "pages": [], "targets": [ "AKT" ], "biomarkers": [], "subtypes": [], "limits": "Associations in heterogeneous preclinical models do not validate a clinical selection assay or a universal AKT dependency. This study does not establish the later PIK3CA/AKT1/PTEN clinical biomarker panel or patient benefit. Sensitivity varied across models.", "label": "AZD5363 functional AKT pharmacology", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "AKT inhibition across molecularly characterized tumor models", "population": "A multi-cancer cell-line panel and xenografts, including trastuzumab-resistant HER2-positive breast models", "claim": "AZD5363 reduced phosphorylation of AKT substrates and showed selective antiproliferative activity; breast cancer cell lines were the most frequently sensitive. PIK3CA or PTEN mutations were associated with sensitivity, whereas RAS mutations were associated with resistance. Breast xenografts, including trastuzumab-resistant HER2-positive models, showed tumor-growth inhibition; selected combinations increased antitumor activity.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PD0332991pre09", "trial": null, "papers": [ { "key": "P-PD0332991pre09", "pmid": "19874578", "title": "PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro.", "journal": "Breast Cancer Res", "year": "2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19874578/", "doi": "10.1186/bcr2419", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [], "limits": "This is an in-vitro study without patient outcomes. Expression patterns associated with response are candidate explanations, not validated patient-selection rules. ER positivity in these models is not equivalent to the clinical HR-positive/HER2-negative category, and findings in selected HER2-amplified lines must not be generalized to all HER2-positive disease.", "label": "PD 0332991 functional breast cell-line study", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "CDK4/6 inhibition across breast cell-line subgroups", "population": "Molecularly characterized human breast cancer and immortalized cell lines", "claim": "Luminal estrogen-receptor-positive models, including HER2-amplified lines, were more sensitive to PD 0332991 than nonluminal or basal models. Sensitive cells showed cell-cycle arrest and reduced Rb phosphorylation. The inhibitor enhanced the activity of tamoxifen or trastuzumab in the corresponding models.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-SGpre15", "trial": null, "papers": [ { "key": "P-SGpre15", "pmid": "25915780", "title": "Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers.", "journal": "Bioconjug Chem", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25915780/", "doi": "10.1021/acs.bioconjchem.5b00223", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [], "subtypes": [], "limits": "The curated evidence is the nonclinical gastric model, not the clinical trial mentioned in the abstract. ADC activity does not prove that tumor growth depends on endogenous Trop-2 signaling. No clinical expression threshold, breast treatment sequence, or patient survival effect is established.", "label": "IMMU-132 functional gastric xenograft evidence", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Trop-2-directed ADC characterization and gastric xenograft activity", "population": "Human tumor cells and gastric cancer xenografts in mice; the paper also studies other cancers", "claim": "IMMU-132 retained Trop-2 binding and induced DNA-damage and apoptotic signaling in tumor cells. In mice bearing human gastric tumors, the targeted conjugate produced stronger antitumor effects than a nonspecific control. Antibody-dependent cellular cytotoxicity was reduced relative to the unconjugated antibody.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PD1Rupp22", "trial": null, "papers": [ { "key": "P-PD1Rupp22", "pmid": "35339889", "title": "Anti-CTLA-4 and anti-PD-1 immunotherapies repress tumor progression in preclinical breast and colon model with independent regulatory T cells response.", "journal": "Transl Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35339889/", "doi": "10.1016/j.tranon.2022.101405", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "This is mouse-model evidence, not a clinical comparison of approved human antibodies. The reported metastasis reduction concerned CTLA-4 blockade in the colon model and must not be attributed to PD-1 blockade in breast cancer. The study does not validate a clinical PD-L1 assay threshold or establish benefit in an unselected human TNBC population.", "label": "PD-1 blockade in syngeneic TNBC models", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Preclinical checkpoint blockade, alone and with CTLA-4 blockade", "population": "Murine syngeneic triple-negative breast cancer models; the paper also studied colon cancer models", "claim": "Murine PD-1 and CTLA-4 blocking antibodies each showed anticancer activity in syngeneic breast and colon cancer models. Their combination enhanced activity in the triple-negative breast cancer model. The antibodies produced different changes in tumor immune infiltration.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PDL1Glyco16", "trial": null, "papers": [ { "key": "P-PDL1Glyco16", "pmid": "27572267", "title": "Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity.", "journal": "Nat Commun", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27572267/", "doi": "10.1038/ncomms12632", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [], "subtypes": [], "limits": "Mechanistic cellular and mouse evidence does not establish clinical efficacy of gefitinib plus PD-1 blockade or of an anti-PD-L1 drug. The work does not validate gastric CPS or the clinical breast PD-L1 selection assay. Basal-like model biology is not evidence that every model meets a clinical TNBC definition.", "label": "PD-L1 glycosylation and immune suppression", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Preclinical regulation of PD-L1 stability and antitumor immunity", "population": "Basal-like breast cancer cellular studies and syngeneic mouse tumor models", "claim": "PD-L1 glycosylation limited its interaction with GSK3beta and the associated protein-degradation pathway. EGF signaling stabilized PD-L1 in basal-like breast cancer. Gefitinib destabilized PD-L1 and enhanced antitumor T-cell activity and the effect of PD-1 blockade in syngeneic mouse models.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-VEGFR2Mashima21", "trial": null, "papers": [ { "key": "P-VEGFR2Mashima21", "pmid": "34302038", "title": "Neutralization of the induced VEGF-A potentiates the therapeutic effect of an anti-VEGFR2 antibody on gastric cancer in vivo.", "journal": "Sci Rep", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34302038/", "doi": "10.1038/s41598-021-94584-9", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "This is a mouse xenograft study, not a clinical ramucirumab combination trial. Host-derived VEGF-A and angiogenesis effects do not prove that human gastric tumor cells are intrinsically dependent on KDR. The model does not establish human safety, benefit, or a patient-selection biomarker for dual blockade.", "label": "VEGFR2 blockade and host VEGF-A feedback", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Preclinical antiangiogenic antibody treatment, alone and with VEGF-A neutralization", "population": "Human gastric cancer xenografts in BALB/c-nu/nu mice", "claim": "VEGFR2 antibody treatment increased circulating host-derived VEGF-A in the gastric cancer xenograft model. Adding VEGF-A neutralization strengthened antitumor activity. The combination produced intratumor changes associated with angiogenesis inhibition and reduced ZEB1 expression, which the study linked to gastric cancer cell proliferation.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PARPRottenberg08", "trial": null, "papers": [ { "key": "P-PARPRottenberg08", "pmid": "18971340", "title": "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.", "journal": "Proc Natl Acad Sci U S A", "year": "2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18971340/", "doi": "10.1073/pnas.0806092105", "errata": [] } ], "pages": [], "targets": [ "PARP1" ], "biomarkers": [], "subtypes": [], "limits": "These outcomes belong to a BRCA1-deficient mouse model and do not establish human efficacy, cure, or benefit in all triple-negative breast cancers. The pharmacologic result does not isolate PARP1 from all other drug effects. Engineered BRCA1 deficiency does not validate a clinical germline BRCA1/2 testing criterion; acquired resistance precludes a claim of durable eradication.", "label": "PARP inhibition in BRCA1-deficient mammary tumors", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "Preclinical PARP inhibition and acquired resistance in BRCA1-associated mammary cancer", "population": "A genetically engineered mouse model of BRCA1-associated breast cancer", "claim": "AZD2281 suppressed mammary tumor growth and prolonged survival in a BRCA1-deficient mouse model. Resistance later developed with increased expression of P-glycoprotein efflux genes. Combining AZD2281 with platinum drugs prolonged recurrence-free and overall survival in the model.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-FGFR2Xie13", "trial": null, "papers": [ { "key": "P-FGFR2Xie13", "pmid": "23493349", "title": "FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547.", "journal": "Clin Cancer Res", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23493349/", "doi": "10.1158/1078-0432.CCR-12-3898", "errata": [] } ], "pages": [], "targets": [ "FGFR2" ], "biomarkers": [], "subtypes": [], "limits": "AZD4547 inhibits FGFR1-3, so its activity alone does not establish FGFR2-exclusive pharmacology; the genetic perturbation supplies separate supporting evidence. Selected amplified models do not establish clinical response across heterogeneous tumors. Amplification is not interchangeable with FGFR2b protein-expression selection, and ERBB2 co-amplification was not validated as a selection biomarker.", "label": "FGFR2-amplified gastric cancer dependency", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "Preclinical FGFR-pathway inhibition and functional dependency", "population": "FGFR2-amplified gastric cancer cells, cell-derived xenografts and patient-derived gastric cancer xenografts, with nonamplified comparator models", "claim": "AZD4547 reduced FGFR2-pathway signaling and inhibited growth in FGFR2-amplified gastric cancer models; the reported tumor-growth inhibition did not extend to nonamplified models. Genetic reduction of FGFR2 also impaired growth in vitro and in vivo, supporting functional dependence in the amplified models.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-FLOT4", "trial": "G-FLOT4", "papers": [ { "key": "P-FLOT4", "pmid": "30982686", "title": "Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.", "journal": "Lancet", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30982686/", "doi": "10.1016/S0140-6736(18)32557-1", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This open-label comparison evaluates complete perioperative regimens, so it does not isolate the effect of postoperative treatment alone. The reported population combines gastric and gastro-oesophageal junction disease. Longer overall survival does not establish cure or the benefit of a ctDNA-guided strategy.", "label": "FLOT4 perioperative chemotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Randomized perioperative chemotherapy, phase 2/3", "population": "Locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma without distant metastases", "claim": "Among 716 randomized patients, intention-to-treat overall survival favored perioperative FLOT over ECF/ECX: median survival was 50 versus 35 months (HR 0·77; 95% CI 0.63-0·94). Related serious adverse events were reported in 27% of patients in each group.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "G-FLOT4", "nct": "NCT01216644", "acronym": null, "title": "5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced, Resectable Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 716, "sponsor": "Krankenhaus Nordwest", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2010-08", "lastUpdate": "2019-06-19", "url": "https://clinicaltrials.gov/study/NCT01216644" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (superiority) in the intention-to-treat population", "primary_endpoint_type": "OS", "design": { "phase": "2/3", "randomized": true, "blinding": "open-label", "n_randomized": 716, "assessment": "not stated", "quote": "In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases" }, "effect": { "measure": "HR", "value": 0.77, "ci_low": 0.63, "ci_high": 0.94, "ci_level": "95%", "p": null, "endpoint": "Overall survival", "quote": "Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26])." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "two [<1%] in both groups", "quote": "The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group." }, "takeaway_en": "In 716 patients with locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX (HR 0.77, 95% CI 0.63–0.94; median overall survival 50 vs 35 months). Related serious adverse events were similar (27% in each group), and there were two toxic deaths in each group.", "takeaway_ko": "국소 진행성 절제 가능 위암 또는 위식도 접합부 선암 환자 716명에서 수술 전후 FLOT 요법은 ECF/ECX 요법보다 전체생존기간을 개선했습니다(위험비 0.77, 95% 신뢰구간 0.63–0.94; 중앙 전체생존기간 50개월 대 35개월). 치료 관련 중대한 이상반응은 양군 모두 27%로 비슷했고, 독성 사망은 각 군 2명이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ctDNAYang20", "trial": null, "papers": [ { "key": "P-ctDNAYang20", "pmid": "32393783", "title": "Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer.", "journal": "Cell Death Dis", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32393783/", "doi": "10.1038/s41419-020-2531-z", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This is a prognostic association from a small observational cohort, not evidence that acting on ctDNA improves survival. The reported hazard ratio concerns detection at any postoperative follow-up time, rather than a single postoperative landmark. A lead over imaging measures detection timing, not additional survival or proof that recurrence can be prevented.", "label": "Postoperative ctDNA recurrence cohort (Yang 2020)", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Postoperative molecular residual disease and longitudinal recurrence surveillance", "population": "Stage I-III gastric cancer after resection with curative intent", "claim": "In a prospective cohort of 46 patients, ctDNA positivity at any time during postoperative follow-up was associated with poorer disease-free survival than no detection (HR 14.78; 95% CI 7.991-61.29). Molecular detection preceded radiographic recurrence by a median of 6 months.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ctDNAYuan23", "trial": "G-ctDNAYuan23", "papers": [ { "key": "P-ctDNAYuan23", "pmid": "37837629", "title": "Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer.", "journal": "Cancer Commun (Lond)", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37837629/", "doi": "10.1002/cac2.12494", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This registered study is observational, not a randomized test of ctDNA-guided treatment. Postoperative and post-adjuvant results belong to different sampling landmarks; their hazard ratios are not a head-to-head comparison of treatment benefit. The abstract states the published cohort total but does not give a separate post-adjuvant analysis denominator. Prognostic discrimination does not establish benefit from treatment escalation or de-escalation based on the assay.", "label": "Post-adjuvant ctDNA recurrence cohort (Yuan 2023)", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Postoperative and post-adjuvant chemotherapy recurrence-risk assessment", "population": "Stage II-III resectable gastric cancer in the published prospective cohort", "claim": "The published cohort enrolled 100 patients. The HR for recurrence in postoperative ctDNA-positive versus ctDNA-negative patients was 2.74 (95% CI 1.37-5.48). At a separate assessment within 3 months after adjuvant chemotherapy, the HR for positivity versus negativity was 14.99 (95% CI 3.08-72.96). Both measurements were reported as independent prognostic factors for recurrence-free survival.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "G-ctDNAYuan23", "nct": "NCT02887612", "acronym": null, "title": "ctDNA for Prediction of Relapse in Gastric Cancer", "status": "UNKNOWN", "phases": [], "enrollment": 200, "sponsor": "Sun Yat-sen University", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2016-09", "lastUpdate": "2019-02-26", "url": "https://clinicaltrials.gov/study/NCT02887612" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-KATHERINE", "trial": "B-KATHERINE", "papers": [ { "key": "P-KATHERINE25", "pmid": "39813643", "title": "Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39813643/", "doi": "10.1056/NEJMoa2406070", "errata": [] }, { "key": "P-KATHERINEneg22", "pmid": "36117201", "title": "Adjuvant trastuzumab emtansine in HER2-positive breast cancer patients with HER2-negative residual invasive disease in KATHERINE.", "journal": "NPJ Breast Cancer", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36117201/", "doi": "10.1038/s41523-022-00477-z", "errata": [] }, { "key": "P-KATHERINEneg25", "pmid": "40148195", "title": "Switching to T-DM1 remains justified in patients with HER2-negative residual invasive breast cancer after neoadjuvant therapy.", "journal": "Breast", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40148195/", "doi": "10.1016/j.breast.2025.104450", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [ "B-HER2POS" ], "limits": "This open-label trial selected patients with residual invasive disease after neoadjuvant therapy. The invasive disease-free survival analysis is final, but the overall survival analysis is the second interim analysis. These findings do not establish cure or automatically apply to patients with a pathological complete response. Earlier and later reports of KATHERINE remain one trial, not independent evidence units. The residual-HER2 subgroup was small and unevenly allocated (28 versus 42), with residual status unknown at randomization; it was not a separately powered trial. The initial report classified some IHC 0/1+ specimens with unknown ISH as negative. The 2025 Viewpoint updates the same subgroup, not an independent replication. It does not establish an interaction with HER2 status, absence of HER2 in every tumour cell, or benefit from using retesting to select treatment.", "label": "KATHERINE · long-term residual-disease follow-up", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Post-neoadjuvant adjuvant therapy; final invasive disease-free survival and second interim overall survival analyses", "population": "HER2-positive early breast cancer with residual invasive disease in the breast or axilla after taxane-based chemotherapy and trastuzumab", "claim": "At a median follow-up of 8.4 years, adjuvant T-DM1 versus trastuzumab yielded 7-year invasive disease-free survival of 80.8% versus 67.1% (unstratified HR for invasive disease or death 0.54, 95% CI 0.44–0.66). The second interim overall survival analysis reported 7-year survival of 89.1% versus 84.4% (unstratified HR for death 0.66, 95% CI 0.51–0.87). Grade 3 or higher adverse events occurred in 26.1% versus 15.7%. In an exploratory subset of patients whose residual disease was HER2-negative on retesting (70/845 patients with assessable paired specimens), the later report gave a 7-year IDFS of 95.2% with T-DM1 versus 60.3% with trastuzumab after a median follow-up of 8 years.", "by": "Codex (GPT-6)", "added": "2026-09-28", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-KATHERINE", "nct": "NCT01772472", "acronym": null, "title": "A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1486, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "NSABP Foundation Inc", "GBG Forschungs GmbH" ], "hasResults": true, "start": "2013-04-03", "lastUpdate": "2025-07-22", "url": "https://clinicaltrials.gov/study/NCT01772472" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (prespecified final analysis); overall survival reported as second interim analysis", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "The primary analysis of KATHERINE, a phase 3, open-label trial … We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles." }, "effect": { "measure": "HR", "value": 0.54, "ci_low": 0.44, "ci_high": 0.66, "ci_level": "95%", "p": null, "endpoint": "Invasive disease-free survival (invasive disease or death), unstratified", "quote": "With a median follow-up of 8.4 years, T-DM1 sustained the improvement in invasive disease-free survival over trastuzumab (unstratified hazard ratio for invasive disease or death, 0.54; 95% confidence interval [CI], 0.44 to 0.66)." }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "7 years", "experimental_pct": 80.8, "control_pct": 67.1, "higher_is_better": true, "experimental_arm": "T-DM1", "control_arm": "Trastuzumab", "quote": "Seven-year invasive disease-free survival was 80.8% with T-DM1 and 67.1% with trastuzumab (difference, 13.7 percentage points).", "difference_pp": 13.7, "nnt": 8, "quote_note": "P-KATHERINE25 (median follow-up 8.4 years" }, { "endpoint": "Overall survival", "timepoint": "7 years", "experimental_pct": 89.1, "control_pct": 84.4, "higher_is_better": true, "experimental_arm": "T-DM1", "control_arm": "Trastuzumab", "quote": "Seven-year overall survival was 89.1% with T-DM1 and 84.4% with trastuzumab (difference, 4.7 percentage points).", "difference_pp": 4.7, "nnt": 22, "quote_note": "P-KATHERINE25 (second interim OS analysis, median follow-up 8.4 years" }, { "endpoint": "Invasive disease-free survival, exploratory subgroup with HER2-negative residual disease on retesting (70 patients)", "timepoint": "7 years", "experimental_pct": 95.2, "control_pct": 60.3, "higher_is_better": true, "experimental_arm": "T-DM1", "control_arm": "Trastuzumab", "quote": "With 8 years of median follow-up, 7-year IDFS was 60.3 % with trastuzumab compared to 95.2 % with T-DM1, consistent with clinically meaningful benefit from T-DM1 in these 70 patients.", "difference_pp": 34.9, "nnt": 3, "quote_note": "P-KATHERINEneg25 (more recent subgroup report, 8 years median follow-up, supersedes 2022 event counts" } ], "harms": { "grade3plus_experimental_pct": 26.1, "grade3plus_control_pct": 15.7, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Adverse events of grade 3 or higher were noted in 26.1% of the patients in the T-DM1 group and 15.7% of those in the trastuzumab group." }, "takeaway_en": "In patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane-based chemotherapy plus trastuzumab, 14 cycles of adjuvant T-DM1 were compared with trastuzumab; at a median follow-up of 8.4 years, 7-year invasive disease-free survival was 80.8% versus 67.1% (13.7 percentage points) and 7-year overall survival was 89.1% versus 84.4% (4.7 percentage points). The trade-off was more grade 3 or higher adverse events with T-DM1 (26.1% versus 15.7%).", "takeaway_ko": "HER2 양성 조기 유방암에서 탁산 기반 항암화학요법과 트라스투주맙 선행요법 후 잔존 침윤성 병변이 있는 환자를 대상으로 보조요법 T-DM1 14주기와 트라스투주맙을 비교했으며, 추적관찰 기간 중앙값 8.4년에서 7년 무침습질환생존율은 80.8% 대 67.1%(13.7%p 차이), 7년 전체생존율은 89.1% 대 84.4%(4.7%p 차이)였습니다. 대신 3등급 이상 이상반응은 T-DM1군에서 더 많았습니다(26.1% 대 15.7%).", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-IMP030", "trial": "B-IMP030", "papers": [ { "key": "P-IMP030", "pmid": "39883436", "title": "Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.", "journal": "JAMA", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39883436/", "doi": "10.1001/jama.2024.26886", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "Enrollment and atezolizumab were stopped after a planned interim and futility analysis; this open-label trial then underwent a premature final analysis. The confidence interval does not establish equivalence or statistically confirmed harm. The study did not randomize preoperative versus postoperative immunotherapy, so comparisons with other trials cannot isolate treatment timing as the cause of different results.", "label": "ALEXANDRA/IMpassion030 · surgery-first adjuvant immunotherapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Adjuvant chemotherapy with or without atezolizumab after surgery as initial treatment", "population": "Patients with stage II or III triple-negative breast cancer undergoing surgery first", "claim": "At a median follow-up of 32 months, adding atezolizumab to postoperative chemotherapy did not improve invasive disease-free survival compared with chemotherapy alone (stratified HR 1.11, 95% CI 0.87–1.42; P = .38). Treatment-related grade 3 or 4 adverse events were more frequent with atezolizumab plus chemotherapy: 54% versus 44%. Fatal adverse events occurred in 0.8% versus 0.6%.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "B-IMP030", "nct": "NCT03498716", "acronym": "IMpassion030", "title": "A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer", "status": "TERMINATED", "phases": [ "PHASE3" ], "enrollment": 2199, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "Breast International Group", "Alliance Foundation Trials, LLC.", "Jules Bordet Institute", "Frontier Science & Technology Research Foundation, Inc." ], "hasResults": true, "start": "2018-08-02", "lastUpdate": "2024-08-21", "url": "https://clinicaltrials.gov/study/NCT03498716" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (time between randomization and invasive breast cancer in the same or opposite breast, recurrence elsewhere in the body, or death from any cause)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 2199, "assessment": "not stated", "quote": "In this open-label international randomized phase 3 trial conducted in more than 330 centers in 31 countries, patients undergoing surgery as initial treatment for stage II or III triple-negative breast cancer were enrolled … Patients were randomized (1:1) to receive standard chemotherapy for 20 weeks with (n = 1101) or without (n = 1098) the immune therapy drug atezolizumab for up to 1 year … The study independent data monitoring committee halted enrollment at 2199 of 2300 planned patients." }, "effect": { "measure": "HR", "value": 1.11, "ci_low": 0.87, "ci_high": 1.42, "ci_level": "95%", "p": ".38", "endpoint": "Invasive disease-free survival (stratified, final analysis; median follow-up 32 months)", "quote": "With invasive disease-free survival events in 141 patients (12.8%) treated with atezolizumab-chemotherapy and 125 (11.4%) with chemotherapy alone (median follow-up, 32 months), the final stratified invasive disease-free survival hazard ratio was 1.11 (95% CI, 0.87-1.42; P = .38)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 54, "grade3plus_control_pct": 44, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Fatal adverse events (attribution not specified): 0.8% vs 0.6%", "quote": "Compared with chemotherapy alone, the regimen of atezolizumab plus chemotherapy was associated with more treatment-related grade 3 or 4 adverse events (54% vs 44%) but similar incidences of fatal adverse events (0.8% vs 0.6%) and adverse events leading to chemotherapy discontinuation." }, "takeaway_en": "In patients with stage II or III triple-negative breast cancer treated with surgery first, this trial compared adding atezolizumab for up to 1 year to postoperative chemotherapy against chemotherapy alone. At a median follow-up of 32 months, invasive disease-free survival did not improve (HR 1.11, 95% CI 0.87-1.42; P = .38), while treatment-related grade 3 or 4 adverse events were more common with atezolizumab (54% vs 44%) and fatal adverse events were similar (0.8% vs 0.6%).", "takeaway_ko": "수술을 먼저 시행한 2기 또는 3기 삼중음성 유방암 환자에서, 이 시험은 수술 후 항암화학요법에 아테졸리주맙(최대 1년)을 추가한 군과 항암화학요법 단독군을 비교했습니다. 추적관찰 기간 중앙값 32개월에서 침습적 무질병 생존은 개선되지 않았고(위험비 1.11, 95% 신뢰구간 0.87-1.42; P = .38), 치료 관련 3-4등급 이상반응은 아테졸리주맙군에서 더 많았으며(54% 대 44%) 치명적 이상반응 발생률은 비슷했습니다(0.8% 대 0.6%).", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-cTRAKTN", "trial": "B-cTRAKTN", "papers": [ { "key": "P-cTRAKTN", "pmid": "36423745", "title": "Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.", "journal": "Ann Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36423745/", "doi": "10.1016/j.annonc.2022.11.005", "errata": [] }, { "key": "P-ctDNAAssays24", "pmid": "38078899", "title": "Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer.", "journal": "Clin Cancer Res", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38078899/", "doi": "10.1158/1078-0432.CCR-23-2326", "errata": [] }, { "key": "P-ctDNATissueFree26", "pmid": "42593771", "title": "Tissue-Free vs Tumor-Informed ctDNA Assays for Molecular Residual Disease Detection in Early Triple Negative Breast Cancer.", "journal": "JAMA Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42593771/", "doi": "10.1001/jamaoncol.2026.2833", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "The initial randomized intervention-versus-observation component was amended by closing observation and assigning subsequent ctDNA-positive patients to intervention. Detection and treatment denominators differ. The very small treated subgroup and amended allocation do not establish comparative recurrence-prevention or survival benefit, or universal pembrolizumab inefficacy. The saved abstract provides no treatment-toxicity estimate; absence of a reported estimate is not evidence of safety. The assay comparisons are exploratory analyses of stored samples; an earlier detection time is not shown to improve outcome, and in the trial itself most patients already had metastases when ctDNA was first found by digital PCR.", "label": "c-TRAK TN · ctDNA surveillance and triggered intervention", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Phase II prospective ctDNA surveillance with a ctDNA-triggered pembrolizumab intervention", "population": "Early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy, or stage II/III disease treated with adjuvant chemotherapy", "claim": "Of 161 patients who entered ctDNA surveillance, 27.3% (44/161; 95% CI 20.6%–34.9%) had ctDNA detected by 12 months. Seven patients relapsed without earlier ctDNA detection. Of those allocated to intervention, 72% (23/32) already had metastases on staging when ctDNA was detected. Five patients began pembrolizumab; none achieved sustained ctDNA clearance. In later analyses of the trial's surveillance samples, a personalised multimutation sequencing assay was the first to detect residual disease in 47.9% of patients and digital PCR was first in 0%; the median lead time to relapse was 6.1 versus 3.9 months (P = 0.004). A tissue-free assay tested on 1026 plasma samples from 159 patients detected ctDNA in 54 patients (34.0%); detection was strongly associated with recurrence (HR 27.2; 95% CI 13.7-54.2). Its median lead time was 7.9 months versus 5.8 months for digital PCR, and 7.6 versus 7.1 months for a multivariant tumour-informed assay (P = .15).", "updated": "2026-10-07", "updatedBy": "Claude (assay comparison papers added); original by Codex (GPT-6)", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "B-cTRAKTN", "nct": "NCT03145961", "acronym": "c-TRAK-TN", "title": "A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients", "status": "UNKNOWN", "phases": [ "PHASE2" ], "enrollment": 208, "sponsor": "Institute of Cancer Research, United Kingdom", "sponsorClass": "OTHER", "collaborators": [ "National Institute for Health Research Biomedical Research Centre at the Royal Marsden / Institute of Cancer Research UK", "Merck Sharp & Dohme LLC" ], "hasResults": false, "start": "2017-12-21", "lastUpdate": "2022-02-24", "url": "https://clinicaltrials.gov/study/NCT03145961" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Co-primary: (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab", "primary_endpoint_type": "other", "design": { "phase": "2", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR … ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention … A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": null, "endpoint": null, "quote": null }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In early triple-negative breast cancer at moderate-to-high risk after neoadjuvant or adjuvant chemotherapy, three-monthly digital-PCR ctDNA surveillance detected ctDNA in 27.3% (44/161) of patients by 12 months, but 72% (23/32) of those allocated to intervention already had metastases on staging, and none of the five who started pembrolizumab achieved sustained ctDNA clearance. Later analyses of the same samples found that personalised multimutation sequencing and a tissue-free assay detected ctDNA earlier than digital PCR (median lead time to relapse 6.1 vs 3.9 months, and 7.9 vs 5.8 months); the abstracts report no treatment-effect comparison between arms and no harms data.", "takeaway_ko": "선행 또는 보조 항암화학요법 후 재발 위험이 중등도~고위험인 조기 삼중음성 유방암 환자에서 3개월 간격 디지털 PCR 기반 ctDNA 감시를 시행했습니다. 12개월까지 27.3%(44/161)에서 ctDNA가 검출되었으나, 중재군에 배정된 환자의 72%(23/32)는 병기 검사에서 이미 원격 전이가 확인되었고, 펨브롤리주맙을 시작한 5명 중 지속적 ctDNA 소실에 도달한 환자는 없었습니다. 같은 검체를 이용한 후속 분석에서는 개인맞춤형 다중변이 시퀀싱과 조직 비의존(tissue-free) 검사가 디지털 PCR보다 ctDNA를 더 일찍 검출했습니다(재발까지 중앙 선행시간 6.1개월 대 3.9개월, 7.9개월 대 5.8개월). 초록에는 군 간 치료 효과 비교와 이상반응 자료가 보고되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DYNAMIC", "trial": null, "papers": [ { "key": "P-DYNAMIC22", "pmid": "35657320", "title": "Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35657320/", "doi": "10.1056/NEJMoa2200075", "errata": [] }, { "key": "P-DYNAMIC25", "pmid": "40055522", "title": "Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40055522/", "doi": "10.1038/s41591-025-03579-w", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Randomization tested management strategies, not chemotherapy versus observation among ctDNA-positive patients. Noninferiority within the specified margin does not establish identical risk or direct benefit from chemotherapy in a positive subgroup. Negative ctDNA does not prove eradication. Later clearance analyses include post hoc findings. The saved abstracts do not quantify toxicity. The two reports are one trial; its ANZCTR registration is not an NCT.", "label": "DYNAMIC · ctDNA-guided stage II colon adjuvant strategy", "registry": { "system": "ANZCTR", "id": "ACTRN12615000381583", "url": "https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000381583" }, "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant management after resection; randomized ctDNA-guided versus standard clinicopathological strategy", "population": "Patients with resected stage II colon cancer", "claim": "Adjuvant chemotherapy use was lower with ctDNA-guided management than with standard management: 15% versus 28%. The primary 2-year recurrence-free survival analysis met noninferiority: 93.5% versus 92.4%, a difference of 1.1 percentage points (95% CI -4.1 to 6.2; prespecified margin -8.5 percentage points). At 59.7 months median follow-up, 5-year recurrence-free survival was 88% versus 87% (difference 1.1%, 95% CI -5.8% to 8.0%); 5-year overall survival was 93.8% versus 93.3%.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-NICHE2", "trial": "C-NICHE2", "papers": [ { "key": "P-NICHE2", "pmid": "38838311", "title": "Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38838311/", "doi": "10.1056/NEJMoa2400634", "errata": [] }, { "key": "P-NICHE2DFS26", "pmid": "42906564", "title": "Disease-free survival and overall survival after neoadjuvant immunotherapy in mismatch repair-deficient colon cancer in the Netherlands: results of the single-arm, multicentre, phase 2, NICHE-2 trial.", "journal": "Lancet", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42906564/", "doi": "10.1016/S0140-6736(26)01602-8", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "This single-arm study does not establish superiority over a randomized comparator. Pathological response in resected tissue does not justify surgery omission or prove cure. The initial report lacked mature prespecified disease-free survival, but the 2026 follow-up now reports that endpoint; the earlier claim time point is retained above. Surgical, efficacy and safety denominators differ. Both PD-1 and CTLA-4 blockade were given, so activity cannot be assigned to nivolumab alone; the target list contains only the existing PDCD1 entity. Follow-up endpoints were evaluated per protocol, not in every screened or treated participant. The exploratory post-hoc overall survival endpoint and its enrollment origin differ from the primary postoperative disease-free survival endpoint. Reported event-free estimates and boundary confidence limits do not establish zero future risk, complete follow-up of every person or cure; numbers at risk, censoring and interval methods require the full report/SAP. Serial ctDNA analyses have time-specific available-sample denominators, and postoperative negativity is not a trial of ctDNA-guided treatment or surgery omission. The new paper abstract was received; its full report/SAP and individual data were not received or executed.", "label": "NICHE-2 · neoadjuvant dual checkpoint blockade", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Neoadjuvant nivolumab plus ipilimumab followed by planned surgery", "population": "Previously untreated, nonmetastatic, locally advanced dMMR colon cancer", "claim": "After nivolumab plus ipilimumab, 113 of 115 enrolled patients underwent timely surgery. Among 111 patients in the efficacy analysis, 75 (68%) had a pathological complete response. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%). No recurrence was reported at a median follow-up of 26 months. The 2026 follow-up reported 3-year disease-free survival of 100% in the 111-patient per-protocol population, with median postoperative follow-up of 58.7 months. Exploratory post-hoc 5-year overall survival was 100%; disease-free survival started at surgery whereas overall survival started at enrollment. This is follow-up of the same trial, not an independent cohort.", "by": "Codex (GPT-6)", "added": "2026-09-28", "updated": "2026-10-24", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "C-NICHE2", "nct": "NCT03026140", "acronym": "NICHE", "title": "Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer", "status": "RECRUITING", "phases": [ "PHASE2" ], "enrollment": 353, "sponsor": "The Netherlands Cancer Institute", "sponsorClass": "OTHER", "collaborators": [ "Bristol-Myers Squibb" ], "hasResults": false, "start": "2017-03-29", "lastUpdate": "2026-09-30", "url": "https://clinicaltrials.gov/study/NCT03026140" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-DOSTrectal", "trial": "C-DOSTrectal", "papers": [ { "key": "P-DOSTrectal22", "pmid": "35660797", "title": "PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35660797/", "doi": "10.1056/NEJMoa2201445", "errata": [] }, { "key": "P-DOSTnonop25", "pmid": "40293177", "title": "Nonoperative Management of Mismatch Repair-Deficient Tumors.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40293177/", "doi": "10.1056/NEJMoa2404512", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "Clinical complete response is not pathological confirmation in a resected specimen or proof of permanent eradication. There is no randomized comparator. Completer and sustained-response counts must not be converted into a recurrence rate. The expanded paper also includes nonrectal tumors; pooled recurrence-free survival and safety are not rectal-only estimates and are omitted here. The early safety observation does not establish absence of later toxicity. Both papers report the same registered trial.", "label": "Dostarlimab · dMMR rectal organ preservation", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Neoadjuvant dostarlimab with response-adapted nonoperative management", "population": "Locally advanced dMMR rectal cancer; only the rectal cohort is summarized from the expanded study", "claim": "The initial rectal-cohort report found a clinical complete response in all 12 patients who completed treatment, and no grade 3 or higher adverse events were reported. In the expanded report, all 49 patients in the rectal cohort who completed treatment had a clinical complete response and chose nonoperative management; 37 patients had a sustained clinical complete response at 12 months.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "C-DOSTrectal", "nct": "NCT04165772", "acronym": null, "title": "Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors", "status": "RECRUITING", "phases": [ "PHASE2" ], "enrollment": 212, "sponsor": "Memorial Sloan Kettering Cancer Center", "sponsorClass": "OTHER", "collaborators": [ "Tesaro, Inc." ], "hasResults": false, "start": "2019-12-11", "lastUpdate": "2026-10-23", "url": "https://clinicaltrials.gov/study/NCT04165772" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-KN177", "trial": "C-KN177", "papers": [ { "key": "P-KN177final", "pmid": "35427471", "title": "Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study.", "journal": "Lancet Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35427471/", "doi": "10.1016/S1470-2045(22)00197-8", "errata": [] }, { "key": "P-KN1775y", "pmid": "39631622", "title": "Pembrolizumab versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase III KEYNOTE-177 study.", "journal": "Ann Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39631622/", "doi": "10.1016/j.annonc.2024.11.012", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "The later survival estimate does not replace the prespecified final overall-survival testing result. Crossover to checkpoint inhibitors complicates the survival contrast. The toxicity comparison above comes from the formal final report, not the later abstract with different adverse-event wording. Long survival and durable response in metastatic disease do not establish a cure fraction. Both publications are one randomized trial, and findings do not extend to microsatellite-stable colorectal cancer.", "label": "KEYNOTE-177 · final analysis and long-term follow-up", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First-line pembrolizumab versus chemotherapy in metastatic disease", "population": "Previously untreated MSI-H or dMMR metastatic colorectal cancer", "claim": "At the formal final analysis, pembrolizumab versus chemotherapy improved median progression-free survival (16·5 versus 8·2 months; HR 0·59). Overall-survival superiority was not established (HR 0·74, 95% CI 0·53–1·03; p=0·036 against the prespecified threshold 0·025). Treatment-related grade 3 or worse adverse events occurred in 22% versus 66% of patients. At the later 73.3-month median follow-up, median overall survival was 77.5 versus 36.7 months (HR 0.73, 95% CI 0.53–0.99), and median response duration was 75.4 versus 10.6 months.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "C-KN177", "nct": "NCT02563002", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 307, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-11-30", "lastUpdate": "2024-10-03", "url": "https://clinicaltrials.gov/study/NCT02563002" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-T-SELECT", "trial": "T-SELECT", "papers": [ { "key": "P-T-SELECT15", "pmid": "25671254", "title": "Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25671254/", "doi": "10.1056/NEJMoa1406470", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary endpoint was PFS; median overall survival remained unreached in both arms. Placebo patients could receive open-label lenvatinib after progression. The drug-related deaths are an attribution within the lenvatinib arm, not an estimate of a between-arm mortality effect. These findings do not establish cure.", "label": "SELECT (lenvatinib)", "program": "thyroid", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Systemic lenvatinib versus placebo; randomized, double-blind comparison.", "population": "Patients with progressive iodine-refractory differentiated thyroid cancer; 261 assigned to lenvatinib and 131 to placebo.", "claim": "Lenvatinib yielded a median PFS of 18.3 months versus 3.6 months with placebo (HR for progression or death 0.21; 99% CI 0.14 to 0.31). Response rates were 64.8% versus 1.5%. Adverse effects led to study-drug discontinuation in 14.2% versus 2.3%. Among 20 deaths during treatment in the lenvatinib arm, 6 were judged drug-related.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-SELECT", "nct": "NCT01321554", "acronym": "SELECT", "title": "A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 392, "sponsor": "Eisai Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2011-03-17", "lastUpdate": "2023-06-22", "url": "https://clinicaltrials.gov/study/NCT01321554" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-DECISION", "trial": "T-DECISION", "papers": [ { "key": "P-T-DECISION14", "pmid": "24768112", "title": "Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial.", "journal": "Lancet", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24768112/", "doi": "10.1016/S0140-6736(14)60421-9", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "PFS was the primary endpoint, and crossover to open-label sorafenib was allowed after progression. The safety and intention-to-treat populations have different denominators. The saved abstract does not establish an overall-survival benefit or cure; effect sizes should not be directly ranked against other trials with different populations.", "label": "DECISION", "program": "thyroid", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Systemic sorafenib versus placebo; randomized, double-blind comparison.", "population": "Adults with locally advanced or metastatic radioiodine-refractory differentiated thyroid cancer progressing within the previous 14 months; 417 randomized patients, with 207 assigned to sorafenib and 210 to placebo.", "claim": "Median PFS was 10·8 months with sorafenib and 5·8 months with placebo (HR 0·59; 95% CI 0·45-0·76). In the safety population, adverse events affected 204/207 patients receiving sorafenib (98·6%) and 183/209 receiving placebo (87·6%). Hand-foot skin reaction occurred in 76·3% of the sorafenib group.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-DECISION", "nct": "NCT00984282", "acronym": null, "title": "Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 417, "sponsor": "Bayer", "sponsorClass": "INDUSTRY", "collaborators": [ "Amgen" ], "hasResults": true, "start": "2009-10-15", "lastUpdate": "2018-09-13", "url": "https://clinicaltrials.gov/study/NCT00984282" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-COSMIC311", "trial": "T-COSMIC311", "papers": [ { "key": "P-T-COSMIC31121", "pmid": "34237250", "title": "Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34237250/", "doi": "10.1016/S1470-2045(21)00332-6", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This report combines a primary ORR analysis with a preplanned interim PFS analysis; the endpoints use different populations. ORR did not pass its predefined threshold despite the positive PFS result. Placebo crossover was permitted after confirmed progression. These data do not establish overall-survival benefit or cure.", "label": "COSMIC-311", "program": "thyroid", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Later lines; cabozantinib versus placebo after progression on prior VEGFR-targeted therapy, randomized and double-blind.", "population": "Radioiodine-refractory differentiated thyroid cancer previously treated with lenvatinib or sorafenib; 187 patients in the ITT population, while primary ORR was assessed in the first 100 randomized patients (OITT).", "claim": "The prespecified interim PFS endpoint was met in the 187-patient ITT population: median PFS was not reached with cabozantinib versus 1·9 months with placebo (HR 0·22; 96% CI 0·13-0·36). In the first 100 patients, analysed separately, ORR was 15% among 67 cabozantinib recipients versus 0% among 33 placebo recipients; p=0·028 did not meet the prespecified alpha of 0·01. Grade 3 or 4 adverse events occurred in 57% versus 26%.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-COSMIC311", "nct": "NCT03690388", "acronym": null, "title": "A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 187, "sponsor": "Exelixis", "sponsorClass": "INDUSTRY", "collaborators": [ "Ipsen" ], "hasResults": true, "start": "2018-10-05", "lastUpdate": "2026-10-20", "url": "https://clinicaltrials.gov/study/NCT03690388" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-LIBRETTO531", "trial": "T-LIBRETTO531", "papers": [ { "key": "P-T-LIBRETTO53123", "pmid": "37870969", "title": "Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37870969/", "doi": "10.1056/NEJMoa2309719", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This was the protocol-specified interim efficacy analysis, with blinded independent central assessment and permitted crossover after progression. Treatment failure-free survival includes progression, discontinuation due to treatment-related adverse events, or death and is not overall survival. The control was cabozantinib or vandetanib, not placebo. Results apply to RET-mutant medullary disease, not all thyroid cancers, and do not establish cure.", "label": "LIBRETTO-531", "program": "thyroid", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First-line selpercatinib versus physician-selected cabozantinib or vandetanib in a randomized trial of advanced RET-mutant medullary thyroid cancer.", "population": "Patients with RET-mutant medullary thyroid cancer and documented recent progression; 291 randomized patients.", "claim": "At a median follow-up of 12 months, median PFS was not reached with selpercatinib versus 16.8 months with the active control (HR 0.28; 95% CI 0.16 to 0.48). The treatment failure-free survival HR was 0.25 (95% CI 0.15 to 0.42). Adverse events prompted dose reduction in 38.9% versus 77.3% and treatment discontinuation in 4.7% versus 26.8%.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-LIBRETTO531", "nct": "NCT04211337", "acronym": "LIBRETTO-531", "title": "A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 291, "sponsor": "Loxo Oncology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Eli Lilly and Company" ], "hasResults": true, "start": "2020-02-11", "lastUpdate": "2026-03-19", "url": "https://clinicaltrials.gov/study/NCT04211337" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-LIBRETTO001", "trial": "T-LIBRETTO001", "papers": [ { "key": "P-T-LIBRETTO00120", "pmid": "32846061", "title": "Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.", "journal": "N Engl J Med", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32846061/", "doi": "10.1056/NEJMoa2005651", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "These are separate uncontrolled cohorts, not randomized comparative effects. Absence of prior vandetanib/cabozantinib does not imply absence of all previous treatment. The wider safety denominator must not be combined with thyroid efficacy denominators or interpreted as a thyroid-specific risk estimate. Response and follow-up PFS do not establish cure or superiority to other therapies.", "label": "LIBRETTO-001 (thyroid cohorts)", "program": "thyroid", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Selpercatinib in a noncomparative trial with separately reported RET-altered thyroid cancer cohorts.", "population": "RET-mutant medullary thyroid cancer with or without prior vandetanib/cabozantinib, and previously treated RET fusion-positive thyroid cancer.", "claim": "Independent-review response rates were 69% in 55 patients with RET-mutant medullary cancer previously treated with vandetanib/cabozantinib, 73% in 88 patients with medullary cancer without that prior exposure, and 79% in 19 previously treated patients with RET fusion-positive thyroid cancer. The corresponding 1-year PFS estimates were 82%, 92%, and 64%. In the wider study population of all treated patients, 12/531 (2%) stopped selpercatinib because of drug-related adverse events; this safety denominator was not limited to thyroid cancer.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-LIBRETTO001", "nct": "NCT03157128", "acronym": "LIBRETTO-001", "title": "A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1", "PHASE2" ], "enrollment": 857, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [ "Loxo Oncology, Inc." ], "hasResults": true, "start": "2017-05-02", "lastUpdate": "2026-04-16", "url": "https://clinicaltrials.gov/study/NCT03157128" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-ROAR", "trial": "T-ROAR", "papers": [ { "key": "P-T-ROAR22", "pmid": "35026411", "title": "Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.", "journal": "Ann Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35026411/", "doi": "10.1016/j.annonc.2021.12.014", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This small, nonrandomized thyroid cohort had no concurrent control; observed survival estimates cannot establish a causal survival improvement or cure. Its denominator is not the entire basket enrollment or the earlier response-assessable subset. The abstract does not quantify adverse-event frequency or severity, and no new safety signal does not mean absence of toxicity. Results do not establish redifferentiation or efficacy in unselected thyroid cancer.", "label": "ROAR (anaplastic thyroid cohort)", "program": "thyroid", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Dabrafenib plus trametinib in the anaplastic thyroid cancer cohort of an open-label, nonrandomized basket study.", "population": "The updated full cohort of 36 patients with unresectable or metastatic BRAF V600E-mutant anaplastic thyroid cancer.", "claim": "In the 36-patient anaplastic thyroid cohort, investigator-assessed ORR was 56% (95% CI 38.1% to 72.1%), including three complete responses. At a median follow-up of 11.1 months, observed median PFS and OS were 6.7 and 14.5 months, respectively; the 24-month OS estimate was 31.5%. The update reported no new safety signals.", "by": "Codex (GPT-6)", "added": "2026-09-28", "trialRecord": { "key": "T-ROAR", "nct": "NCT02034110", "acronym": null, "title": "Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 206, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-03-12", "lastUpdate": "2023-08-21", "url": "https://clinicaltrials.gov/study/NCT02034110" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-KoreaThyScreen16", "trial": null, "papers": [ { "key": "P-KoreaThyScreen16", "pmid": "27627550", "title": "Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality.", "journal": "Thyroid", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27627550/", "doi": "10.1089/thy.2016.0075", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This is a regional ecological analysis, not an individual screened-versus-unscreened follow-up comparison. It does not identify individual overdiagnosis or establish a causal screening benefit or harm. Self-reported screening, regional confounding and nonidentical incidence and mortality observation periods limit interpretation. Lack of an observed regional mortality association does not prove zero effect in every individual. Diagnostic and treatment harms were not quantified in the saved abstract.", "program": "thyroid", "by": "Codex (GPT-6)", "added": "2026-09-28", "label": "Korean thyroid screening · regional incidence and mortality", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Ecological regional association of opportunistic screening with thyroid cancer incidence and disease-specific mortality", "population": "Korean administrative regions; screening data from 226,873 respondents to the 2010 Korea Community Health Survey, national cancer-registry incidence and national mortality statistics", "claim": "Regional screening correlated with thyroid cancer incidence (r=0.77; 95% CI 0.70-0.82) and papillary cancer detection (r=0.74; CI 0.59-0.88). No regional association with thyroid cancer mortality was observed (r=-0.08; CI -0.59-0.63).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HashimotoPTC17", "trial": null, "papers": [ { "key": "P-HashimotoPTC17", "pmid": "28977955", "title": "A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk.", "journal": "Oncotarget", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28977955/", "doi": "10.18632/oncotarget.18620", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This synthesis is not a population-based cohort. Surgical specimens select patients who undergo thyroidectomy; clinical FNA samples and selectively tested groups are not automatically representative of the general population. The publisher full text includes an insurance-based cohort among heterogeneous designs and describes differing populations, surgery indications and diagnostic criteria. Its sampling-method table shows confidence intervals crossing the null for FNA and selective-FNA strata, despite broad supportive language in the abstract. Selection, detection and residual confounding remain plausible explanations; the pooled association does not establish that thyroiditis causes cancer.", "program": "thyroid", "by": "Codex (GPT-6)", "added": "2026-09-28", "label": "Hashimoto thyroiditis and papillary cancer · observational meta-analysis", "kind": "analysis", "level": "literature", "result": "descriptive", "setting": "Random-effects meta-analysis of observational associations, with heterogeneous sampling and diagnostic methods", "population": "76,281 patients across studies using archival thyroidectomy specimens, fine-needle aspiration (FNA), or selective FNA/thyroidectomy sampling", "claim": "The overall pooled odds ratio for papillary thyroid carcinoma in patients with versus without Hashimoto thyroiditis was 2.12 (95% CI 1.78-2.52). This describes an observational association across differing sampling methods, not a causal effect.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2Residual26", "trial": null, "papers": [ { "key": "P-HER2Residual26", "pmid": "42803995", "title": "HER2 status change in residual breast carcinoma after neoadjuvant HER2-targeted therapy in patients with HER2-positive breast cancer.", "journal": "Breast Cancer Res Treat", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42803995/", "doi": "10.1007/s10549-026-08088-z", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The single-institution retrospective sample selects assessable residual invasive tumours; its conversion frequency cannot be applied to all treated patients. The abstract does not explain the disposition of every other treated patient or establish that all excluded patients had a complete response. Post-treatment IHC/FISH classification does not by itself distinguish clonal change from sampling or assay variation, establish functional drug resistance, or demonstrate benefit from changing adjuvant treatment. No recurrence or survival comparison is reported in this abstract.", "label": "HER2 change in residual tumour after neoadjuvant therapy", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Post-neoadjuvant residual invasive tumour assessment; single-institution retrospective pathology study", "population": "Initially HER2-positive breast cancer treated with HER2-targeted neoadjuvant therapy, restricted to cases with sufficient residual invasive tumour for reassessment", "claim": "Among 161 treated patients, 65 had adequate residual invasive tumour for HER2 assessment. HER2 overexpression was retained in 28/65 (43%), while 37/65 (57%) changed to IHC 0/1+ or IHC 2+/FISH non-amplified. These frequencies refer to the subset with assessable residual tumour.", "by": "Codex (GPT-6)", "added": "2026-09-29", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-MATTERHORN", "trial": "G-MATTERHORN", "papers": [ { "key": "P-MATTERHORN", "pmid": "40454643", "title": "Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40454643/", "doi": "10.1056/NEJMoa2503701", "errata": [] }, { "key": "P-MATTERHORNOS", "pmid": "42716074", "title": "Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.", "journal": "Lancet", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42716074/", "doi": "10.1016/S0140-6736(26)01254-7", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [], "subtypes": [], "limits": "The earlier OS analysis had not met its stricter significance boundary; the later final result updates the same trial. The randomized comparison evaluates the entire perioperative strategy and cannot separate preoperative, postoperative or maintenance contributions. The initial report recorded grade 3 or 4 adverse events in 71.6% vs 71.2%. The final report recorded possibly treatment-related fatal events in 6/475 vs 2/469 treated participants. Pathological response is not a validated statement of cure, and these findings do not establish benefit in unresectable disease.", "label": "MATTERHORN", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Perioperative durvalumab plus FLOT followed by durvalumab versus matched placebo plus FLOT followed by placebo", "population": "Previously untreated, resectable stage II-IVa gastric or gastroesophageal junction adenocarcinoma eligible for radical surgery", "claim": "The initial report found 2-year EFS of 67.4% vs 58.5% (HR 0.71, 95% CI 0.58-0.86). The later final OS analysis reported HR 0·78 (95% CI 0·63-0·96; P=0·021), meeting its prespecified significance threshold of P<0·0499.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-MATTERHORN", "nct": "NCT04592913", "acronym": null, "title": "Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 957, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2020-11-17", "lastUpdate": "2025-12-24", "url": "https://clinicaltrials.gov/study/NCT04592913" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Event-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 948, "assessment": "not stated", "quote": "From Nov 17, 2020, to Sept 2, 2022, 1258 participants were enrolled and 948 were randomly assigned; 474 were randomly assigned to durvalumab and 474 to placebo. … MATTERHORN is a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial … Participants, investigators, and those assessing outcomes were masked." }, "effect": { "measure": "HR", "value": 0.71, "ci_low": 0.58, "ci_high": 0.86, "ci_level": "95%", "p": "<0.001", "endpoint": "Event-free survival", "quote": "Two-year event-free survival (Kaplan-Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group (hazard ratio for event or death, 0.71; 95% confidence interval [CI], 0.58 to 0.86; P<0.001)." }, "landmark": [ { "endpoint": "Event-free survival", "timepoint": "2 years", "experimental_pct": 67.4, "control_pct": 58.5, "higher_is_better": true, "experimental_arm": "Durvalumab + FLOT, then durvalumab", "control_arm": "Placebo + FLOT, then placebo", "quote": "Two-year event-free survival (Kaplan-Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group", "difference_pp": 8.9, "nnt": 12, "quote_note": "Initial report (NEJM 2025, median follow-up 31.5 months; not updated in the final Lancet 2026 abstract" }, { "endpoint": "Overall survival", "timepoint": "2 years", "experimental_pct": 75.7, "control_pct": 70.4, "higher_is_better": true, "experimental_arm": "Durvalumab + FLOT, then durvalumab", "control_arm": "Placebo + FLOT, then placebo", "quote": "Two-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group", "difference_pp": 5.3, "nnt": 19, "quote_note": "Interim figure from the initial report (NEJM 2025); the final OS paper (Lancet 2026) gives no landmark percentages" }, { "endpoint": "Pathological complete response", "timepoint": "After neoadjuvant therapy and surgery", "experimental_pct": 19.2, "control_pct": 7.2, "higher_is_better": true, "experimental_arm": "Durvalumab + FLOT", "control_arm": "Placebo + FLOT", "quote": "The percentage of participants with a pathological complete response was 19.2% in the durvalumab group and 7.2% in the placebo group (relative risk, 2.69 [95% CI, 1.86 to 3.90]).", "difference_pp": 12, "nnt": 9, "quote_note": "Initial report (NEJM 2025" } ], "harms": { "grade3plus_experimental_pct": 71.6, "grade3plus_control_pct": 71.2, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Adverse events with the outcome of death possibly related to any trial treatment: 6 (1%) of 475 participants with durvalumab vs 2 (<1%) of 469 with placebo", "quote": "Adverse events with a maximum grade of 3 or 4 were reported in 340 participants (71.6%) in the durvalumab group and in 334 (71.2%) in the placebo group. … Adverse events with the outcome of death possibly related to any trial treatment occurred in 6 (1%) of 475 participants in the durvalumab group and 2 (<1%) of 469 participants in the placebo group.", "quote_note": "Lancet 2026; NEJM 2025; grade 3 or 4 only, grade 5 not included in this figure" }, "takeaway_en": "In 948 patients with previously untreated, resectable stage II–IVa gastric or gastroesophageal junction adenocarcinoma, adding perioperative durvalumab to FLOT raised 2-year event-free survival from 58.5% to 67.4%, raised pathological complete response from 7.2% to 19.2%, and improved overall survival in the final analysis (HR 0·78, 95% CI 0·63–0·96). Grade 3–4 adverse events were similar (71.6% vs 71.2%), while deaths possibly related to treatment numbered 6 with durvalumab versus 2 with placebo.", "takeaway_ko": "이전 치료력이 없는 절제 가능한 II–IVa기 위암 또는 위식도접합부 선암 환자 948명에서 FLOT 수술 전후 항암화학요법에 durvalumab을 추가하자 2년 무사건 생존율이 58.5%에서 67.4%로, 병리학적 완전관해율이 7.2%에서 19.2%로 높아졌습니다. 최종 분석에서 전체 생존도 개선되었습니다(위험비 0·78, 95% 신뢰구간 0·63–0·96). 3–4등급 이상반응 빈도는 비슷했으나(71.6% 대 71.2%), 치료와 관련 가능성이 있는 사망은 durvalumab군 6명, 위약군 2명이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB05", "trial": "B-DB05", "papers": [ { "key": "P-DB05", "pmid": "41370739", "title": "Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41370739/", "doi": "10.1056/NEJMoa2514661", "errata": [ { "pmid": "41931063", "title": "Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/41931063/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "This open-label comparison selected a high-risk residual-disease population; it does not cover all HER2-positive early disease or all patients with residual tumour. The reported IDFS improvement does not itself establish an OS benefit or cure. Gastrointestinal and hematologic toxicity also occurred. The full publisher correction was reviewed. It restores a corrupted Discussion passage about lower IHC scores with ISH amplification and distant recurrence; it does not amend the IDFS or ILD estimates cited here. The original full article and underlying patient data were not independently audited. Biomarker changes after neoadjuvant therapy alone do not establish which treatment an individual patient should receive.", "label": "DESTINY-Breast05", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Postneoadjuvant trastuzumab deruxtecan versus trastuzumab emtansine after surgery", "population": "HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment and either node-positive disease at surgery or inoperable disease at diagnosis", "claim": "At a median follow-up of approximately 30 months, 3-year invasive disease-free survival was 92.4% with trastuzumab deruxtecan vs 83.7% with trastuzumab emtansine (HR 0.47, 95% CI 0.34-0.66). Adjudicated drug-related interstitial lung disease occurred in 9.6% vs 1.6%; two patients with interstitial lung disease in the deruxtecan group died.", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-DB05", "nct": "NCT04622319", "acronym": null, "title": "A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 1600, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca", "NSABP Foundation Inc", "GBG Forschungs GmbH", "Spanish Breast Cancer Research Group" ], "hasResults": false, "start": "2020-12-04", "lastUpdate": "2026-05-15", "url": "https://clinicaltrials.gov/study/NCT04622319" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 1635, "assessment": "not stated", "quote": "In a phase 3, open-label, international, randomized trial … A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients)." }, "effect": { "measure": "HR", "value": 0.47, "ci_low": 0.34, "ci_high": 0.66, "ci_level": "95%", "p": "P<0.001", "endpoint": "Invasive disease-free survival", "quote": "Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001)" }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "3 years", "experimental_pct": 92.4, "control_pct": 83.7, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan (T-DXd)", "control_arm": "Trastuzumab emtansine (T-DM1)", "quote": "3-year invasive disease-free survival was 92.4% and 83.7%, respectively.", "difference_pp": 8.7, "nnt": 12, "quote_note": "P-DB05, the only paper provided; median follow-up approximately 30 months" }, { "endpoint": "Disease-free survival", "timepoint": "3 years", "experimental_pct": 92.3, "control_pct": 83.5, "higher_is_better": true, "experimental_arm": "Trastuzumab deruxtecan (T-DXd)", "control_arm": "Trastuzumab emtansine (T-DM1)", "quote": "3-year disease-free survival was 92.3% and 83.5%, respectively.", "difference_pp": 8.8, "nnt": 12, "quote_note": "P-DB05, the only paper provided; median follow-up approximately 30 months" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Two patients with interstitial lung disease in the T-DXd group died.", "quote": "The incidence of adjudicated drug-related interstitial lung disease was higher with T-DXd than with T-DM1 (9.6% vs. 1.6%). Two patients with interstitial lung disease in the T-DXd group died." }, "takeaway_en": "In patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant therapy and node-positive disease at surgery or inoperable disease at diagnosis, postneoadjuvant trastuzumab deruxtecan was compared with trastuzumab emtansine, and 3-year invasive disease-free survival was 92.4% versus 83.7% (HR 0.47) at about 30 months of median follow-up. The main trade-off was more adjudicated drug-related interstitial lung disease with trastuzumab deruxtecan (9.6% vs 1.6%), and two patients with interstitial lung disease in the trastuzumab deruxtecan group died.", "takeaway_ko": "선행항암치료 후 침윤성 잔존암이 남아 있고 수술 시 림프절 양성이거나 진단 시 수술 불가능했던 HER2 양성 조기 유방암 환자에서 수술 후 보조요법으로 트라스투주맙 데룩스테칸과 트라스투주맙 엠탄신을 비교한 결과, 추적관찰 중앙값 약 30개월 시점에 3년 무침윤질환생존율은 92.4% 대 83.7%였습니다(위험비 0.47). 주요 trade-off는 트라스투주맙 데룩스테칸군에서 판정위원회가 약물 관련으로 판정한 간질성 폐질환이 더 많았다는 점이며(9.6% 대 1.6%), 트라스투주맙 데룩스테칸군에서 간질성 폐질환 환자 2명이 사망했습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ASCENT04", "trial": "B-ASCENT04", "papers": [ { "key": "P-ASCENT04", "pmid": "41564397", "title": "Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41564397/", "doi": "10.1056/NEJMoa2508959", "errata": [] } ], "pages": [], "targets": [ "TACSTD2", "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "The open-label trial evaluated a selected PD-L1-positive population and a combination strategy; both groups received pembrolizumab. It cannot isolate each drug contribution or establish the same effect in unselected TNBC, earlier disease or later treatment lines. PFS improvement is not evidence of an OS benefit or cure. Adverse-event-related deaths are not necessarily adjudicated treatment-related deaths.", "label": "ASCENT-04 / KEYNOTE-D19", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First systemic treatment for advanced disease; sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab", "population": "PD-L1-positive, locally advanced unresectable or metastatic triple-negative breast cancer without prior systemic therapy for advanced disease", "claim": "Median centrally reviewed PFS was 11.2 vs 7.8 months (HR 0.65, 95% CI 0.51-0.84; P<0.001). Overall-survival data were immature. Grade >=3 adverse events occurred in 71% vs 70%, and adverse events leading to death in 3% of each group.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ASCENT04", "nct": "NCT05382286", "acronym": "ASCENT-04", "title": "Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 443, "sponsor": "Gilead Sciences", "sponsorClass": "INDUSTRY", "collaborators": [ "Merck Sharp & Dohme LLC" ], "hasResults": false, "start": "2022-07-25", "lastUpdate": "2025-09-18", "url": "https://clinicaltrials.gov/study/NCT05382286" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by blinded independent central review", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 443, "assessment": "blinded independent central review", "quote": "In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. … A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients)." }, "effect": { "measure": "HR", "value": 0.65, "ci_low": 0.51, "ci_high": 0.84, "ci_level": "95%", "p": "two-sided P<0.001", "endpoint": "Progression-free survival (disease progression or death), blinded independent central review", "quote": "The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P<0.001)." }, "landmark": [ { "endpoint": "Objective response (complete or partial response), blinded independent central review", "timepoint": "Best response (no fixed time point)", "experimental_pct": 60, "control_pct": 53, "higher_is_better": true, "experimental_arm": "Sacituzumab govitecan plus pembrolizumab", "control_arm": "Chemotherapy plus pembrolizumab", "quote": "The percentage of patients with an objective response was 60% (95% CI, 53 to 66) with sacituzumab govitecan plus pembrolizumab and 53% (95% CI, 46 to 60) with chemotherapy plus pembrolizumab", "difference_pp": 7, "nnt": 15, "quote_note": "single paper, N Engl J Med 2026" } ], "harms": { "grade3plus_experimental_pct": 71, "grade3plus_control_pct": 70, "discontinuation_experimental_pct": 12, "discontinuation_control_pct": 31, "treatment_related_deaths": "Treatment-related deaths not separately reported; adverse events leading to death occurred in 3% of the patients in each group", "quote": "Adverse events of grade 3 or higher occurred in 71% of the patients receiving sacituzumab govitecan plus pembrolizumab and in 70% of those receiving chemotherapy plus pembrolizumab; the incidence of treatment discontinuation due to adverse events was 12% and 31%, respectively. Adverse events leading to death occurred in 3% of the patients in each group." }, "takeaway_en": "In 443 patients with previously untreated, PD-L1-positive, locally advanced unresectable or metastatic triple-negative breast cancer, sacituzumab govitecan plus pembrolizumab achieved an objective response in 60% vs 53% with chemotherapy plus pembrolizumab, and extended centrally reviewed median progression-free survival to 11.2 vs 7.8 months (HR 0.65, 95% CI 0.51-0.84); overall-survival data were immature. Grade 3 or higher adverse events were similar (71% vs 70%), discontinuation due to adverse events was lower (12% vs 31%), and adverse events leading to death occurred in 3% of each group.", "takeaway_ko": "이전에 치료받지 않은 PD-L1 양성 국소 진행성 절제 불가능 또는 전이성 삼중음성 유방암 환자 443명에서, 사시투주맙 고비테칸과 펨브롤리주맙 병용군의 객관적 반응률은 60%로, 항암화학요법과 펨브롤리주맙 병용군의 53%보다 높았습니다. 맹검 독립 중앙 판정에 따른 무진행 생존기간 중앙값도 11.2개월 대 7.8개월로 연장되었으나(위험비 0.65, 95% 신뢰구간 0.51-0.84), 전체 생존 자료는 아직 미성숙합니다. 3등급 이상 이상반응은 71% 대 70%로 비슷했고, 이상반응으로 인한 치료 중단은 12% 대 31%로 더 적었으며, 사망에 이른 이상반응은 두 군 모두 3%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-HER2CLIMB05", "trial": "B-HER2CLIMB05", "papers": [ { "key": "P-HER2CLIMB05", "pmid": "41369677", "title": "HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer.", "journal": "J Clin Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41369677/", "doi": "10.1200/JCO-25-02600", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The blinded placebo-controlled comparison selected patients who had already completed induction without progression. It does not evaluate the whole first-line strategy from diagnosis or establish benefit during progressive induction, after resection of early disease, or in symptomatic brain metastases. PFS is not overall survival or cure. The quoted toxicity proportions describe the tucatinib arm rather than a comparative risk difference. Registry results first appeared in September 2026, whereas the linked article was electronically published in December 2025; these are reports of the same trial, not two independent studies.", "label": "HER2CLIMB-05 · first-line maintenance", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First-line maintenance after trastuzumab, pertuzumab and taxane induction without progression; tucatinib versus placebo added to trastuzumab/pertuzumab", "population": "Centrally confirmed HER2-positive metastatic breast cancer without progression after induction and with no or asymptomatic brain metastases; the randomized cohort was entirely female", "claim": "In the published primary analysis, among 654 randomized patients (326 versus 328), investigator-assessed median PFS was 24.9 versus 16.3 months with tucatinib versus placebo added to trastuzumab/pertuzumab (HR 0.641, 95% CI 0.514–0.799; P<.0001). Overall-survival data were immature in that report. In the tucatinib arm, grade ≥3 diarrhea, elevated ALT and elevated AST occurred in 6.1%, 13.5% and 7.1%, respectively; 13.5% discontinued tucatinib because of treatment-emergent adverse events.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-HER2CLIMB05", "nct": "NCT05132582", "acronym": "HER2CLIMB-05", "title": "A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 654, "sponsor": "Seagen, a wholly owned subsidiary of Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2022-03-07", "lastUpdate": "2026-09-29", "url": "https://clinicaltrials.gov/study/NCT05132582" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 654, "assessment": "investigator", "quote": "Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS) … 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms." }, "effect": { "measure": "HR", "value": 0.641, "ci_low": 0.514, "ci_high": 0.799, "ci_level": "95%", "p": "P < .0001", "endpoint": "Investigator-assessed PFS", "quote": "PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 13.5, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs." }, "takeaway_en": "In women with HER2-positive metastatic breast cancer without progression after first-line induction, adding tucatinib to trastuzumab/pertuzumab maintenance lengthened investigator-assessed progression-free survival compared with placebo (HR 0.641, 95% CI 0.514 to 0.799; median 24.9 v 16.3 months). Overall survival was still immature. In the tucatinib arm, diarrhea occurred in 72.7% (6.1% grade ≥3) and grade ≥3 ALT elevation in 13.5%, and 13.5% stopped tucatinib because of adverse events.", "takeaway_ko": "1차 유도요법 후 진행이 없는 HER2 양성 전이성 유방암 여성 환자에서, 트라스투주맙/퍼투주맙 유지요법에 투카티닙을 추가하자 위약 대비 연구자 평가 무진행생존기간이 연장되었습니다(위험비 0.641, 95% 신뢰구간 0.514–0.799; 중앙값 24.9개월 대 16.3개월). 전체생존 자료는 아직 미성숙합니다. 투카티닙군에서 설사가 72.7%(3등급 이상 6.1%), 3등급 이상 ALT 상승이 13.5%에서 발생했으며, 13.5%가 이상반응으로 투카티닙을 중단했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN585", "trial": "G-KN585", "papers": [ { "key": "P-KN58523", "pmid": "38134948", "title": "Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study.", "journal": "Lancet Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38134948/", "doi": "10.1016/S1470-2045(23)00541-7", "errata": [] }, { "key": "P-KN58525", "pmid": "40829093", "title": "Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40829093/", "doi": "10.1200/JCO-25-00486", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "The final OS interval includes no difference. A later nominal EFS interval does not reverse the unsuccessful prespecified test. The small FLOT cohort is distinct from the main cohort; neither the chemotherapy backbone nor the separate contribution of preoperative and postoperative treatment was randomized against another strategy. Initial and final reports remain one trial.", "label": "KEYNOTE-585 · perioperative pembrolizumab", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Pembrolizumab versus placebo added before and after surgery; main cisplatin-doublet cohort and a separate smaller FLOT cohort", "population": "Previously untreated, locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma", "claim": "In the main cohort (n=804), the initial report found a higher pathological complete response rate, but EFS did not cross its prespecified significance boundary. At final follow-up, median OS was 71.8 versus 55.7 months (HR 0.86, 95% CI 0.71–1.06). Grade ≥3 drug-related adverse events were reported in 65% versus 63% of patients.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-KN585", "nct": "NCT03221426", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1007, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2017-10-09", "lastUpdate": "2026-03-09", "url": "https://clinicaltrials.gov/study/NCT03221426" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Co-primary endpoints: pathological complete response (central review), event-free survival (investigator review), and overall survival in the intention-to-treat population, plus safety", "primary_endpoint_type": "other", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 804, "assessment": "investigator", "quote": "The KEYNOTE-585 study is a multicentre, randomised, placebo-controlled, double-blind, phase 3 study … Primary endpoints were pathological complete response (reviewed centrally), event-free survival (reviewed by the investigator), and overall survival in the intention-to-treat population … 804 were randomly assigned to the main cohort", "quote_note": ". Note: pCR was centrally reviewed and EFS was investigator-assessed. 'investigator' refers to EFS" }, "effect": { "measure": "HR", "value": 0.86, "ci_low": 0.71, "ci_high": 1.06, "ci_level": "95%", "p": null, "endpoint": "Overall survival, main cohort, final analysis", "quote": "After a median follow-up of 59.9 months (range, 39-76), median OS was 71.8 versus 55.7 months (hazard ratio [HR], 0.86 [95% CI, 0.71 to 1.06]) with pembrolizumab plus chemotherapy versus placebo plus chemotherapy in the main cohort.", "quote_note": "P-KN58525, final analysis" }, "landmark": [ { "endpoint": "Pathological complete response", "timepoint": "After neoadjuvant therapy and surgery (interim analysis, median follow-up 47.7 months)", "experimental_pct": 12.9, "control_pct": 2, "higher_is_better": true, "experimental_arm": "Pembrolizumab plus cisplatin-based chemotherapy", "control_arm": "Placebo plus cisplatin-based chemotherapy", "quote": "pembrolizumab was superior to placebo for pathological complete response (52 [12·9%; 95% CI 9·8-16·6] of 402 vs eight [2·0%; 0·9-3·9] of 402; difference 10·9%, 95% CI 7·5 to 14·8; p<0·00001)", "difference_pp": 10.9, "nnt": 10, "quote_note": "P-KN58523 interim. The final paper P-KN58525 reports continued pCR improvement but gives no updated percentages." } ], "harms": { "grade3plus_experimental_pct": 65, "grade3plus_control_pct": 63, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "four (1%) patients in the pembrolizumab group and two (<1%) patients in the placebo group", "quote": "Grade ≥3 drug-related adverse event rates were 65% versus 63%. … Treatment-related adverse events that led to death occurred in four (1%) patients in the pembrolizumab group (interstitial ischaemia, pneumonia, decreased appetite, and acute kidney injury [n=1 each]) and two (<1%) patients in the placebo group (neutropenic sepsis and neutropenic colitis [n=1 each]).", "quote_note": "P-KN58523 interim; the interim paper reported grade 3 or worse adverse events of any cause in 78% vs 74%; P-KN58525 final" }, "takeaway_en": "In previously untreated, locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (main cohort, n=804), adding perioperative pembrolizumab to cisplatin-based chemotherapy raised the pathological complete response rate from 2.0% to 12.9% (difference 10.9%), but event-free survival did not meet its significance threshold, and at final analysis overall survival was not significantly improved (median 71.8 vs 55.7 months; HR 0.86, 95% CI 0.71–1.06). Grade ≥3 drug-related adverse events were similar (65% vs 63%), with treatment-related deaths in 1% versus <1%.", "takeaway_ko": "이전 치료력이 없는 국소진행성 절제 가능 위암 또는 위식도접합부 선암 환자(주 코호트, n=804)에서 시스플라틴 기반 항암화학요법에 수술 전후 펨브롤리주맙을 추가하자 병리학적 완전관해율이 2.0%에서 12.9%로 증가했습니다(차이 10.9%). 그러나 무사건생존은 통계적 유의성 기준을 충족하지 못했고, 최종 분석에서 전체생존도 유의하게 개선되지 않았습니다(중앙값 71.8개월 대 55.7개월; HR 0.86, 95% CI 0.71–1.06). 3등급 이상 약물 관련 이상반응은 65% 대 63%로 비슷했으며, 치료 관련 사망은 1% 대 <1%였습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ATT5", "trial": "G-ATT5", "papers": [ { "key": "P-ATT5", "pmid": "38906161", "title": "Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Gastroenterol Hepatol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38906161/", "doi": "10.1016/S2468-1253(24)00156-0", "errata": [ { "pmid": "40088908", "title": "Correction to Lancet Gastroenterol Hepatol 2024; 9: 705-17.", "url": "https://pubmed.ncbi.nlm.nih.gov/40088908/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "This postoperative comparison does not test a whole perioperative strategy. The efficacy and safety populations differ. The adjusted confidence level is retained as reported. The full publisher correction and current abstract were reviewed: the safety statement uses corrected treatment-related wording, while the primary efficacy estimate remains as quoted. Other corrected tables and deaths are not reproduced here; this is not an independent audit of the full article. Failure to demonstrate benefit does not establish equivalence or exclude every possible subgroup effect.", "label": "ATTRACTION-5 · postoperative nivolumab", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Nivolumab versus placebo added to postoperative S-1 or capecitabine/oxaliplatin after D2 or more extensive lymph-node dissection", "population": "Pathological stage III gastric or gastroesophageal junction adenocarcinoma after gastrectomy; Asian multicentre trial", "claim": "Among 755 randomized patients, the addition of nivolumab did not demonstrate improved relapse-free survival: HR 0·90 (95·72% CI 0·69–1·18; p=0·44). Treatment-related adverse events led to discontinuation in 34 of 371 treated patients in the nivolumab group versus 13 of 374 in the placebo group.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-ATT5", "nct": "NCT03006705", "acronym": null, "title": "Study of Adjuvant ONO-4538 With Resected Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 800, "sponsor": "Ono Pharmaceutical Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [ "Bristol-Myers Squibb" ], "hasResults": false, "start": "2017-01-31", "lastUpdate": "2024-05-03", "url": "https://clinicaltrials.gov/study/NCT03006705" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Relapse-free survival by central assessment", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 755, "assessment": "not stated", "quote": "ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. … The primary endpoint was relapse-free survival by central assessment. … Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378)." }, "effect": { "measure": "HR", "value": 0.9, "ci_low": 0.69, "ci_high": 1.18, "ci_level": "95.72%", "p": "0.44", "endpoint": "Relapse-free survival (95·72% CI)", "quote": "the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44)" }, "landmark": [ { "endpoint": "Relapse-free survival", "timepoint": "3 years", "experimental_pct": 68.4, "control_pct": 65.3, "higher_is_better": true, "experimental_arm": "Nivolumab plus chemotherapy", "control_arm": "Placebo plus chemotherapy", "quote": "3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group", "difference_pp": 3.1, "nnt": 33, "quote_note": "single paper, P-ATT5; median time from first dose to data cutoff 49·1 months" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 9, "discontinuation_control_pct": 4, "treatment_related_deaths": null, "quote": "Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients)." }, "takeaway_en": "In Asian patients with pathological stage III gastric or gastro-oesophageal junction adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, adding nivolumab to adjuvant S-1 or capecitabine plus oxaliplatin did not significantly improve relapse-free survival: 3-year relapse-free survival was 68.4% with nivolumab versus 65.3% with placebo (HR 0.90, 95.72% CI 0.69–1.18; p=0.44). Treatment-related adverse events were nearly universal in both groups (99% vs 98%), and discontinuation due to adverse events was more frequent with nivolumab (9% vs 4%).", "takeaway_ko": "D2 이상 림프절 절제를 동반한 위절제술 후 병리학적 3기 위암 또는 위식도접합부 선암종 아시아 환자에서, 보조 S-1 또는 카페시타빈·옥살리플라틴 요법에 니볼루맙을 추가해도 무재발생존이 유의하게 개선되지 않았습니다. 3년 무재발생존율은 니볼루맙군 68.4%, 위약군 65.3%였습니다(HR 0.90, 95.72% CI 0.69–1.18; p=0.44). 치료 관련 이상반응은 양군 모두에서 거의 전례 발생했으며(99% 대 98%), 이상반응으로 인한 투약 중단은 니볼루맙군에서 더 많았습니다(9% 대 4%).", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CREATEX", "trial": null, "papers": [ { "key": "P-CREATEX", "pmid": "28564564", "title": "Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy.", "journal": "N Engl J Med", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28564564/", "doi": "10.1056/NEJMoa1612645", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS", "B-TNBC" ], "limits": "The trial stopped early after a prespecified interim analysis met the primary endpoint. This open-label comparison tested adding capecitabine, not replacing it with another active drug. The overall HER2-negative result and the triple-negative subgroup are distinct. The study does not establish efficacy after contemporary perioperative immunotherapy.", "label": "CREATE-X · HER2-negative residual disease", "registry": { "system": "UMIN-CTR", "id": "UMIN000000843", "url": "https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000989" }, "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Postoperative capecitabine added to standard care versus standard care without capecitabine after neoadjuvant chemotherapy", "population": "HER2-negative breast cancer with residual invasive disease after anthracycline, taxane, or both; Japanese and South Korean trial", "claim": "Among 910 randomized patients, 5-year DFS was 74.1% versus 67.6% (HR 0.70, 95% CI 0.53–0.92), and OS was 89.2% versus 83.6% (HR 0.59, 95% CI 0.39–0.90). Hand-foot syndrome occurred in 73.4% of capecitabine recipients.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 910, "assessment": "not stated", "quote": "We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival." }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.53, "ci_high": 0.92, "ci_level": "95%", "p": "P=0.01", "endpoint": "Disease-free survival (recurrence, second cancer, or death)", "quote": "hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01" }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "5 years", "experimental_pct": 74.1, "control_pct": 67.6, "higher_is_better": true, "experimental_arm": "Standard postsurgical treatment plus capecitabine", "control_arm": "Standard postsurgical treatment without capecitabine", "quote": "The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years", "difference_pp": 6.5, "nnt": 16 }, { "endpoint": "Overall survival", "timepoint": "5 years", "experimental_pct": 89.2, "control_pct": 83.6, "higher_is_better": true, "experimental_arm": "Standard postsurgical treatment plus capecitabine", "control_arm": "Standard postsurgical treatment without capecitabine", "quote": "Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01)", "difference_pp": 5.6, "nnt": 18, "quote_note": "final analysis, single paper" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group." }, "takeaway_en": "In 910 patients with HER2-negative breast cancer who had residual invasive disease after neoadjuvant anthracycline and/or taxane chemotherapy, adding adjuvant capecitabine to standard postsurgical treatment gave 5-year disease-free survival of 74.1% versus 67.6% and 5-year overall survival of 89.2% versus 83.6% (trial stopped early after the interim analysis met the primary end point). The main trade-off was hand-foot syndrome, which occurred in 73.4% of capecitabine recipients; the abstract does not report grade 3 or higher event rates or discontinuations.", "takeaway_ko": "선행항암화학요법(안트라사이클린 및/또는 탁산) 후 잔존 침습암이 있는 HER2 음성 유방암 환자 910명에서 수술 후 표준치료에 보조 카페시타빈을 추가했을 때 5년 무병생존율은 74.1% 대 67.6%, 5년 전체생존율은 89.2% 대 83.6%였습니다(중간분석에서 일차 평가변수를 충족하여 조기 종료됨). 주요 부작용은 수족증후군으로 카페시타빈군의 73.4%에서 발생했으며, 초록에는 3등급 이상 이상반응 발생률이나 투약 중단율이 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-EA1131", "trial": "B-EA1131", "papers": [ { "key": "P-EA1131", "pmid": "34092112", "title": "Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34092112/", "doi": "10.1200/JCO.21.00976", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "The trial stopped early for futility before the planned full information. An unsuccessful noninferiority test does not prove equivalence or, by itself, a prespecified superiority result for capecitabine. The basal-subtype result should not be generalized to all residual breast cancer, and the study does not isolate modern immunotherapy sequences.", "label": "EA1131 · platinum versus capecitabine", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Postoperative platinum chemotherapy versus capecitabine following neoadjuvant chemotherapy; noninferiority design with a superiority alternative", "population": "Stage II or III triple-negative breast cancer with substantial residual invasive disease; primary efficacy population had PAM50 basal subtype", "claim": "In the 308 patients with basal subtype disease, 3-year invasive DFS was 42% (95% CI 30–53) with platinum versus 49% (39–59) with capecitabine. The monitoring committee recommended stopping because noninferiority or superiority of platinum was unlikely to be shown. Severe toxicities were more frequent with platinum.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-EA1131", "nct": "NCT02445391", "acronym": null, "title": "Platinum in Treating Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 415, "sponsor": "ECOG-ACRIN Cancer Research Group", "sponsorClass": "NETWORK", "collaborators": [ "National Cancer Institute (NCI)" ], "hasResults": true, "start": "2015-10-20", "lastUpdate": "2026-10-02", "url": "https://clinicaltrials.gov/study/NCT02445391" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (iDFS) in patients with PAM50 basal subtype TNBC", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": null, "endpoint": null, "quote": null }, "landmark": [ { "endpoint": "Invasive disease-free survival (basal subtype TNBC)", "timepoint": "3 years", "experimental_pct": 42, "control_pct": 49, "higher_is_better": true, "experimental_arm": "Platinum (carboplatin or cisplatin) every 3 weeks for four cycles", "control_arm": "Capecitabine 14 of 21 days for six cycles", "quote": "After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine.", "difference_pp": -7, "nnt": null, "nnt_label": "favours control", "quote_note": "J Clin Oncol 2021, only report", "nnh": 15 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 and 4 toxicities were more common with platinum agents." }, "takeaway_en": "In patients with stage II–III basal-subtype triple-negative breast cancer and residual disease after neoadjuvant chemotherapy, the trial compared adjuvant platinum with capecitabine. Platinum did not do better: 3-year invasive disease-free survival was 42% with platinum versus 49% with capecitabine, and grade 3–4 toxicities were more common with platinum. The trial was stopped early after a median follow-up of 20 months because noninferiority or superiority of platinum was unlikely to be shown.", "takeaway_ko": "선행항암화학요법 후 잔존 침습성 병변이 있는 2–3기 기저형(basal subtype) 삼중음성 유방암 환자에서 보조요법으로 백금계 약제와 카페시타빈을 비교했습니다. 3년 무침습질환생존율은 백금계군 42%, 카페시타빈군 49%로 백금계 약제의 이점은 없었고, 3–4등급 독성은 백금계군에서 더 흔했습니다. 중앙 추적관찰 기간 20개월 시점에 백금계의 비열등성이나 우월성을 입증하기 어렵다고 판단되어 시험은 조기 중단되었습니다.", "certainty": { "level": "moderate", "reasons": [ "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ACTSGC", "trial": "G-ACTSGC", "papers": [ { "key": "P-ACTSGC07", "pmid": "17978289", "title": "Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine.", "journal": "N Engl J Med", "year": "2007", "url": "https://pubmed.ncbi.nlm.nih.gov/17978289/", "doi": "10.1056/NEJMoa072252", "errata": [ { "pmid": null, "title": "N Engl J Med. 2008 May 1;358(18):1977", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070056", "reviewed": true, "unresolvedIdentifier": true } ] }, { "key": "P-ACTSGC5y", "pmid": "22010012", "title": "Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.", "journal": "J Clin Oncol", "year": "2011", "url": "https://pubmed.ncbi.nlm.nih.gov/22010012/", "doi": "10.1200/JCO.2011.36.5908", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Overall survival was the primary endpoint; relapse-free survival and safety were secondary. The initial efficacy findings were disclosed following the planned interim analysis, and the later report follows the same randomized patients. Surgery alone was the comparator, so the result does not rank S-1 against later active regimens or perioperative strategies. The population and D2 surgery setting should be retained when comparing trials; long-term survival is not proof that every recurrence was prevented. The saved abstract does not give the exact safety-analysis denominator, which must not be inferred from the randomized count. The publisher correction amends an entry in a figure, not the abstract estimates quoted here; its full notice was reviewed.", "label": "ACTS-GC · postoperative S-1 after D2 gastrectomy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Postoperative S-1 versus surgery alone after curative gastrectomy with D2 lymph-node dissection", "population": "Patients in Japan with stage II or III gastric cancer", "claim": "The original report assigned 529 patients to S-1 and 530 to surgery alone. At 5 years, overall survival was 71.7% versus 61.1% (HR 0.669, 95% CI 0.540–0.828), and relapse-free survival was 65.4% versus 53.1% (HR 0.653, 95% CI 0.537–0.793). The original report recorded grade 3 or 4 anorexia in 6.0%, nausea in 3.7% and diarrhea in 3.1% of the S-1 group.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-ACTSGC", "nct": "NCT00152217", "acronym": null, "title": "Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1000, "sponsor": "Taiho Pharmaceutical Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2001-09", "lastUpdate": "2011-07-07", "url": "https://clinicaltrials.gov/study/NCT00152217" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. … Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.", "quote_note": "P-ACTSGC5y title; No combined total is stated in either abstract, so n_randomized is null. Blinding and endpoint assessment method are not reported" }, "effect": { "measure": "HR", "value": 0.669, "ci_low": 0.54, "ci_high": 0.828, "ci_level": "95%", "p": null, "endpoint": "Overall survival (5-year follow-up)", "quote": "The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828).", "quote_note": "P-ACTSGC5y (most recent, 5-year follow-up); The 2007 interim report gave HR 0.68, 95% CI 0.52 to 0.87, P=0.003. No P value is reported at 5 years." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "5 years", "experimental_pct": 71.7, "control_pct": 61.1, "higher_is_better": true, "experimental_arm": "Surgery followed by S-1 for 1 year", "control_arm": "Surgery only", "quote": "The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group", "difference_pp": 10.6, "nnt": 10, "quote_note": "P-ACTSGC5y (most recent, 5-year follow-up; supersedes 3-year OS of 80.1% vs 70.1% in P-ACTSGC07" }, { "endpoint": "Relapse-free survival", "timepoint": "5 years", "experimental_pct": 65.4, "control_pct": 53.1, "higher_is_better": true, "experimental_arm": "Surgery followed by S-1 for 1 year", "control_arm": "Surgery only", "quote": "The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793).", "difference_pp": 12.3, "nnt": 9, "quote_note": "P-ACTSGC5y (most recent, 5-year follow-up" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).", "quote_note": "P-ACTSGC07; Neither abstract reports an overall grade ≥3 rate, discontinuation rates or treatment-related deaths." }, "takeaway_en": "In Japanese patients with stage II or III gastric cancer after gastrectomy with D2 lymph-node dissection, 1 year of adjuvant oral S-1 was compared with surgery alone. At 5 years, overall survival was 71.7% versus 61.1% (HR 0.669) and relapse-free survival was 65.4% versus 53.1%. The most common grade 3 or 4 adverse events with S-1 were anorexia (6.0%), nausea (3.7%) and diarrhea (3.1%). Overall grade 3 or higher toxicity and discontinuation rates were not reported in the abstracts.", "takeaway_ko": "D2 림프절 절제를 동반한 위절제술 후 2기 또는 3기 위암 일본인 환자에서 1년간 경구 S-1 보조항암요법을 수술 단독과 비교했습니다. 5년 전체생존율은 71.7% 대 61.1%(위험비 0.669), 5년 무재발생존율은 65.4% 대 53.1%였습니다. S-1군에서 비교적 흔한 3–4등급 이상반응은 식욕부진 6.0%, 구역 3.7%, 설사 3.1%였습니다. 전체 3등급 이상 이상반응 비율과 치료 중단율은 초록에 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ARTIST2", "trial": "G-ARTIST2", "papers": [ { "key": "P-ARTIST2", "pmid": "33278599", "title": "A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial(☆).", "journal": "Ann Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33278599/", "doi": "10.1016/j.annonc.2020.11.017", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary endpoint was DFS, not overall survival. The abstract's broad conclusion about both combination regimens must be read alongside the different reported P values; it does not describe multiplicity adjustment in detail. The nonsignificant SOX/SOXRT comparison does not establish equivalence, and these postoperative results do not isolate a benefit of preoperative treatment. The abstract contains a truncated trial identifier; the linked ClinicalTrials.gov record separately confirms ARTIST-II and the complete identifier. Safety is described qualitatively without arm-level adverse-event rates in the saved abstract.", "label": "ARTIST 2 · postoperative chemotherapy and radiation", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Adjuvant S-1, S-1/oxaliplatin (SOX), or SOX with chemoradiotherapy (SOXRT) after D2 resection", "population": "Curatively resected, node-positive stage II or III gastric cancer", "claim": "Among 546 patients, estimated 3-year DFS was 64.8% with S-1, 74.3% with SOX and 72.8% with SOXRT. The reported P values were 0.042 for the S-1/SOX comparison and 0.074 for S-1/SOXRT. The SOX versus SOXRT comparison did not show a DFS difference (HR 0.971; P=0.879).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-ARTIST2", "nct": "NCT01761461", "acronym": "ARTIST-II", "title": "Phase III Randomized Trial of Adjuvant Chemotherapy With S-1 vs S-1/Oxaliplatin ± Radiotherapy for Completely Resected Gastric Adenocarcinoma : The ARTIST II Trial", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 547, "sponsor": "Samsung Medical Center", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2013-02-06", "lastUpdate": "2020-03-25", "url": "https://clinicaltrials.gov/study/NCT01761461" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (DFS) at 3 years", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 546, "assessment": "not stated", "quote": "The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens … A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively." }, "effect": { "measure": "HR", "value": 0.692, "ci_low": null, "ci_high": null, "ci_level": null, "p": "0.042", "endpoint": "DFS, S-1 versus SOX (as worded in the abstract; the hazard ratio is reported without a confidence interval)", "quote": "HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879)." }, "landmark": [ { "endpoint": "DFS", "timepoint": "3 years", "experimental_pct": 74.3, "control_pct": 64.8, "higher_is_better": true, "experimental_arm": "S-1 plus oxaliplatin (SOX) for 6 months", "control_arm": "S-1 monotherapy for 1 year", "quote": "Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively.", "difference_pp": 9.5, "nnt": 11, "quote_note": "Ann Oncol 2021, median follow-up 47 months" }, { "endpoint": "DFS", "timepoint": "3 years", "experimental_pct": 72.8, "control_pct": 64.8, "higher_is_better": true, "experimental_arm": "SOX plus chemoradiotherapy 45 Gy (SOXRT)", "control_arm": "S-1 monotherapy for 1 year", "quote": "Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively.", "difference_pp": 8, "nnt": 13, "quote_note": "Ann Oncol 2021, median follow-up 47 months" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable." }, "takeaway_en": "In 546 patients with D2-resected, node-positive stage II/III gastric cancer, estimated 3-year disease-free survival was 74.3% with S-1 plus oxaliplatin (SOX) and 72.8% with SOX plus chemoradiotherapy, versus 64.8% with S-1 alone (S-1 vs SOX HR 0.692, P=0.042; S-1 vs SOXRT HR 0.724, P=0.074), and adding radiotherapy to SOX showed no DFS difference (HR 0.971, P=0.879). The abstract gives no adverse-event rates by arm and states only that toxicities were as anticipated and generally manageable.", "takeaway_ko": "D2 절제술을 받은 림프절 양성 2-3기 위암 환자 546명에서 추정 3년 무병생존율은 S-1+옥살리플라틴(SOX) 군 74.3%, SOX+화학방사선요법(SOXRT) 군 72.8%, S-1 단독군 64.8%였습니다(S-1 대 SOX 위험비 0.692, P=0.042; S-1 대 SOXRT 위험비 0.724, P=0.074). SOX에 방사선치료를 추가해도 무병생존 차이는 없었습니다(위험비 0.971, P=0.879). 초록에는 군별 이상반응 발생률이 제시되지 않았으며, 이상반응은 예상 범위였고 대체로 관리 가능했다고만 기술되어 있습니다.", "certainty": { "level": "moderate", "reasons": [ "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CRITICS", "trial": "G-CRITICS", "papers": [ { "key": "P-CRITICS", "pmid": "29650363", "title": "Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29650363/", "doi": "10.1016/S1470-2045(18)30132-3", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label comparison with allocation before any preoperative chemotherapy; the primary analysis includes patients who never started postoperative treatment. Outcomes among treatment completers would be subject to post-randomization selection. Surgical lymph-node dissection and chemotherapy backbone differ from other perioperative studies. The failed superiority comparison does not prove equivalence or exclude benefit in an untested subgroup. Adverse-event denominators differ between the preoperative safety population and the postoperative treated groups.", "label": "CRITICS · postoperative chemotherapy versus chemoradiotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Perioperative chemotherapy versus preoperative chemotherapy followed by surgery and postoperative chemoradiotherapy; allocation before preoperative treatment", "population": "Resectable gastric or gastroesophageal adenocarcinoma staged IB–IVA by AJCC sixth edition; Netherlands, Sweden and Denmark", "claim": "Among 788 randomized patients, median overall survival was 43 months with chemotherapy versus 37 months with chemoradiotherapy (HR 1·01, 95% CI 0·84–1·22; p=0·90). Only 233 of 393 patients started postoperative chemotherapy and 245 of 395 started postoperative chemoradiotherapy. The primary intention-to-treat analysis did not demonstrate an overall survival benefit from the chemoradiotherapy strategy.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-CRITICS", "nct": "NCT00407186", "acronym": null, "title": "Randomized Phase III Trial of Adjuvant Chemotherapy or Chemoradiotherapy in Resectable Gastric Cancer (CRITICS)", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 788, "sponsor": "Dutch Colorectal Cancer Group", "sponsorClass": "OTHER", "collaborators": [ "The Netherlands Cancer Institute", "Roche Pharma AG" ], "hasResults": false, "start": "2007-01-11", "lastUpdate": "2017-10-10", "url": "https://clinicaltrials.gov/study/NCT00407186" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival, analysed by intention-to-treat", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 788, "assessment": "not stated", "quote": "In this investigator-initiated, open-label, randomised phase 3 trial … Patients and investigators were not masked to treatment allocation … Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395)." }, "effect": { "measure": "HR", "value": 1.01, "ci_low": 0.84, "ci_high": 1.22, "ci_level": "95%", "p": "0·90", "endpoint": "Overall survival (stratified analysis), chemotherapy group vs chemoradiotherapy group", "quote": "At a median follow-up of 61·4 months (IQR 43·3-82·8), median overall survival was 43 months (95% CI 31-57) in the chemotherapy group and 37 months (30-48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1·01 (95% CI 0·84-1·22; p=0·90)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "13 (2%) deaths during preoperative chemotherapy in the pooled safety population of 781; no deaths during postoperative treatment", "quote": "After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths … During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 [34%] of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths were observed during postoperative treatment." }, "takeaway_en": "In 788 patients with resectable stage IB–IVA gastric or gastro-oesophageal adenocarcinoma, all randomised before preoperative chemotherapy and surgery, postoperative chemoradiotherapy did not improve overall survival over postoperative chemotherapy: median overall survival was 37 versus 43 months (HR 1·01, 95% CI 0·84-1·22; p=0·90). Only 59% of the chemotherapy group and 62% of the chemoradiotherapy group started postoperative treatment; among those who did, grade 3 adverse events occurred in 48% versus 41%, grade 4 in 9% versus 4%, and non-febrile neutropenia in 34% versus 4% (chemotherapy versus chemoradiotherapy).", "takeaway_ko": "절제 가능한 IB–IVA기 위암 또는 위식도접합부 선암 환자 788명을 수술 전 항암화학요법과 수술에 앞서 무작위 배정했습니다. 수술 후 항암화학방사선요법은 수술 후 항암화학요법에 비해 전체생존기간을 개선하지 못했으며, 중앙 전체생존기간은 37개월 대 43개월이었습니다(위험비 1·01, 95% CI 0·84-1·22; p=0·90). 수술 후 치료를 시작한 환자는 항암화학요법군 59%, 항암화학방사선요법군 62%에 불과했습니다. 치료를 시작한 환자에서 항암화학요법군 대 항암화학방사선요법군의 3등급 이상반응은 48% 대 41%, 4등급 이상반응은 9% 대 4%, 비발열성 호중구감소증은 34% 대 4%였습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-postMONARCH", "trial": "B-postMONARCH", "papers": [ { "key": "P-postMONARCH", "pmid": "39693591", "title": "Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39693591/", "doi": "10.1200/JCO-24-02086", "errata": [] }, { "key": "P-postMONARCHOS26", "pmid": "42926108", "title": "Overall survival from the phase III postMONARCH trial of abemaciclib plus fulvestrant versus placebo plus fulvestrant for HR-positive, HER2-negative advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42926108/", "doi": "10.1016/j.annonc.2026.10.1283", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "This double-blind trial tested adding a specified CDK inhibitor with a changed endocrine backbone after progression. It does not establish that continuing any prior CDK inhibitor has the same effect, nor does it test a switch triggered by ESR1 detection before progression. The abstract reports nominal P values and different investigator and central-review estimates; they are separate assessments of one trial. The prespecified final OS analysis did not cross its significance boundary. The confidence interval spans benefit, no difference, and possible harm. The updated PFS P value was nominal. The final OS report follows the same randomized participants and adds no independent trial. No new safety signal is not equivalent to no toxicity, and the saved abstracts do not quantify comparative adverse-event rates.", "label": "postMONARCH · abemaciclib after CDK4/6 progression", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Abemaciclib plus fulvestrant versus placebo plus fulvestrant after progression on a previous CDK4/6-based endocrine regimen", "population": "HR-positive, HER2-negative advanced breast cancer progressing after initial CDK4/6 inhibitor plus aromatase inhibitor treatment, or recurring on or after an adjuvant CDK4/6-based endocrine regimen", "claim": "Among 368 randomized patients, investigator-assessed PFS at the primary analysis favored abemaciclib: median 6.0 versus 5.3 months (HR 0.73, 95% CI 0.57–0.95; nominal P=.017). The secondary blinded central review also favored abemaciclib (HR 0.55, 95% CI 0.39–0.77; nominal P<.001). At the prespecified final OS analysis with 200 deaths, median OS was 32.1 versus 24.6 months (HR 0.80, 95% CI 0.60–1.06, P=0.11), short of the prespecified significance boundary (HR 0.753). Updated PFS had HR 0.78 (95% CI 0.62–0.99; nominal P=0.039).", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-11-13", "updatedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-postMONARCH", "nct": "NCT05169567", "acronym": "postMONARCH", "title": "Abemaciclib (LY2835219) Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 368, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2022-03-11", "lastUpdate": "2026-10-06", "url": "https://clinicaltrials.gov/study/NCT05169567" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 368, "assessment": "investigator", "quote": "This double-blind, randomized phase III study enrolled patients with disease progression on previous CDK4/6i plus aromatase inhibitor as initial therapy for advanced disease or recurrence on/after adjuvant CDK4/6i + ET. … The primary end point was investigator-assessed progression-free survival (PFS). … This study randomly assigned 368 patients (abemaciclib + fulvestrant, n = 182 placebo + fulvestrant, n = 186)." }, "effect": { "measure": "HR", "value": 0.73, "ci_low": 0.57, "ci_high": 0.95, "ci_level": "95%", "p": "nominal P = .017", "endpoint": "Investigator-assessed PFS (primary analysis, 258 events)", "quote": "At the primary analysis (258 events), the hazard ratio (HR) was 0.73 (95% CI, 0.57 to 0.95; nominal P = .017), with median PFS 6.0 (95% CI, 5.6 to 8.6) versus 5.3 (95% CI, 3.7 to 5.6) months" }, "landmark": [ { "endpoint": "Investigator-assessed PFS rate", "timepoint": "6 months", "experimental_pct": 50, "control_pct": 37, "higher_is_better": true, "experimental_arm": "Abemaciclib + fulvestrant", "control_arm": "Placebo + fulvestrant", "quote": "6-month PFS rates of 50% and 37% in the abemaciclib + fulvestrant and placebo + fulvestrant arms, respectively", "difference_pp": 13, "nnt": 8, "quote_note": "primary analysis, P-postMONARCH, J Clin Oncol 2025" }, { "endpoint": "Investigator-assessed objective response rate (patients with measurable disease)", "timepoint": "Primary analysis", "experimental_pct": 17, "control_pct": 7, "higher_is_better": true, "experimental_arm": "Abemaciclib + fulvestrant", "control_arm": "Placebo + fulvestrant", "quote": "Among patients with measurable disease, investigator-assessed ORR was improved with abemaciclib + fulvestrant versus placebo + fulvestrant (17% v 7%; nominal P = .015).", "difference_pp": 10, "nnt": 10, "quote_note": "primary analysis, P-postMONARCH, J Clin Oncol 2025" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "No new safety signals were observed, with findings consistent with the known safety profile of abemaciclib." }, "takeaway_en": "In HR-positive, HER2-negative advanced breast cancer that progressed on a prior CDK4/6 inhibitor-based regimen, adding abemaciclib to fulvestrant raised the 6-month progression-free survival rate to 50%, compared with 37% for placebo plus fulvestrant (HR 0.73), and the objective response rate to 17% versus 7%. The abstract reports no new safety signals beyond abemaciclib's known profile, but it gives no grade 3 or higher adverse event or discontinuation rates.", "takeaway_ko": "이전 CDK4/6 억제제 기반 요법 후 진행한 호르몬수용체 양성, HER2 음성 진행성 유방암에서 풀베스트란트에 아베마시클립을 추가하자 6개월 무진행생존율이 위약+풀베스트란트군의 37%에서 50%로 높아졌고(위험비 0.73), 객관적 반응률은 17% 대 7%였습니다. 초록에서는 아베마시클립의 기존 안전성 프로파일 외에 새로운 안전성 신호가 없었다고 보고했으나, 3등급 이상 이상반응률이나 치료 중단율은 제시하지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-MAINTAIN", "trial": "B-MAINTAIN", "papers": [ { "key": "P-MAINTAIN", "pmid": "37207300", "title": "Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: MAINTAIN Trial.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37207300/", "doi": "10.1200/JCO.22.02392", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "This phase II, double-blind trial tested PFS with a prespecified one-sided test. The prior-drug distribution limits generalization to progression after every CDK inhibitor, and the comparison does not establish a class-wide continuation effect. The saved abstract does not establish an overall survival benefit or quantify adverse events. The randomized population in the paper must not be replaced with the different overall enrollment number in the registry summary.", "label": "MAINTAIN · endocrine switch with ribociclib", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Switched endocrine therapy with ribociclib versus switched endocrine therapy with placebo after progression during previous endocrine therapy plus a CDK4/6 inhibitor", "population": "HR-positive, HER2-negative metastatic breast cancer; most randomized participants previously received palbociclib", "claim": "Among 119 randomized participants, 103 (86.5%) had previously received palbociclib. Median PFS was 5.29 months with switched endocrine therapy plus ribociclib versus 2.76 months with switched endocrine therapy plus placebo (HR 0.57, 95% CI 0.39–0.85; P=.006).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-MAINTAIN", "nct": "NCT02632045", "acronym": "MAINTAIN", "title": "Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 169, "sponsor": "Melissa K Accordino", "sponsorClass": "OTHER", "collaborators": [ "Novartis Pharmaceuticals" ], "hasResults": true, "start": "2016-03", "lastUpdate": "2024-12-06", "url": "https://clinicaltrials.gov/study/NCT02632045" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (PFS), defined as time from random assignment to disease progression or death", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "double-blind", "n_randomized": 119, "assessment": "not stated", "quote": "In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2- MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. … Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib" }, "effect": { "measure": "HR", "value": 0.57, "ci_low": 0.39, "ci_high": 0.85, "ci_level": "95%", "p": ".006", "endpoint": "PFS", "quote": "There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006." }, "landmark": [ { "endpoint": "PFS rate", "timepoint": "6 months", "experimental_pct": 41.2, "control_pct": 23.9, "higher_is_better": true, "experimental_arm": "Switched ET plus ribociclib", "control_arm": "Switched ET plus placebo", "quote": "At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo.", "difference_pp": 17.3, "nnt": 6, "quote_note": "P-MAINTAIN, J Clin Oncol 2023; only paper provided" }, { "endpoint": "PFS rate", "timepoint": "12 months", "experimental_pct": 24.6, "control_pct": 7.4, "higher_is_better": true, "experimental_arm": "Switched ET plus ribociclib", "control_arm": "Switched ET plus placebo", "quote": "At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo.", "difference_pp": 17.2, "nnt": 6, "quote_note": "P-MAINTAIN, J Clin Oncol 2023; only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In patients with HR-positive, HER2-negative metastatic breast cancer whose disease progressed on endocrine therapy plus a CDK4/6 inhibitor (mostly palbociclib), switching endocrine therapy (fulvestrant or exemestane) and adding ribociclib was compared with switched endocrine therapy plus placebo; PFS at 12 months was 24.6% with ribociclib versus 7.4% with placebo (HR 0.57). The abstract does not report adverse events, discontinuations, or treatment-related deaths, so the harm trade-off cannot be judged from this source.", "takeaway_ko": "내분비요법과 CDK4/6 억제제(대부분 팔보시클립) 치료 중 진행한 호르몬수용체 양성, HER2 음성 전이성 유방암 환자에서, 내분비요법을 풀베스트란트 또는 엑세메스탄으로 변경하면서 리보시클립을 추가한 군과 위약을 추가한 군을 비교했습니다. 12개월 무진행생존율은 리보시클립군 24.6%, 위약군 7.4%였습니다(위험비 0.57). 초록에는 이상반응, 치료 중단, 치료 관련 사망이 보고되지 않아 위해 측면의 득실은 이 자료로 판단할 수 없습니다.", "certainty": { "level": "moderate", "reasons": [ "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PACE", "trial": "B-PACE", "papers": [ { "key": "P-PACE", "pmid": "38513188", "title": "PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38513188/", "doi": "10.1200/JCO.23.01940", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "The primary question was fulvestrant versus fulvestrant/palbociclib; the avelumab comparison is not evidence of a confirmed immunotherapy benefit. The reported confidence level is retained. The negative primary result does not prove equivalence, exclude all subgroup effects, or test switching to every other CDK inhibitor. Baseline ESR1/PIK3CA subgroup observations are exploratory and are not used here to claim a predictive biomarker. The saved abstract does not quantify toxicity or establish an overall survival benefit.", "label": "PACE · palbociclib continuation after progression", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Fulvestrant alone, fulvestrant/palbociclib, or fulvestrant/palbociclib/avelumab after progression on a CDK4/6 inhibitor plus an aromatase inhibitor", "population": "HR-positive, HER2-negative metastatic breast cancer previously treated with a CDK4/6-based endocrine regimen; most had received palbociclib", "claim": "The trial randomized 220 patients; 90.9% had previously received palbociclib. In the primary comparison, median PFS was 4.8 months with fulvestrant alone versus 4.6 months with fulvestrant/palbociclib (HR 1.11, 90% CI 0.79–1.55; P=.62). Median PFS in the avelumab-containing arm was 8.1 months; the comparison with fulvestrant alone was inconclusive (HR 0.75, 90% CI 0.50–1.12; P=.23).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-PACE", "nct": "NCT03147287", "acronym": null, "title": "Palbociclib After CDK and Endocrine Therapy (PACE)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 220, "sponsor": "Dana-Farber Cancer Institute", "sponsorClass": "OTHER", "collaborators": [ "Pfizer" ], "hasResults": true, "start": "2017-09-05", "lastUpdate": "2026-09-11", "url": "https://clinicaltrials.gov/study/NCT03147287" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS) in patients treated with fulvestrant versus fulvestrant plus palbociclib", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "not stated", "n_randomized": 220, "assessment": "investigator", "quote": "The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P. … Overall, 220 patients were randomly assigned between September 2017 and February 2022." }, "effect": { "measure": "HR", "value": 1.11, "ci_low": 0.79, "ci_high": 1.55, "ci_level": "90%", "p": "P = .62", "endpoint": "PFS, fulvestrant plus palbociclib versus fulvestrant", "quote": "The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In 220 patients with HR-positive/HER2-negative metastatic breast cancer that had progressed on a CDK4/6 inhibitor plus an aromatase inhibitor, adding palbociclib to fulvestrant did not improve progression-free survival (median 4.6 vs 4.8 months; HR 1.11, 90% CI 0.79 to 1.55). The fulvestrant/palbociclib/avelumab arm had a median PFS of 8.1 months, but its comparison with fulvestrant alone was inconclusive (HR 0.75, 90% CI 0.50 to 1.12), and the abstract does not report harms.", "takeaway_ko": "CDK4/6 억제제와 아로마타제 억제제 치료 후 진행한 호르몬수용체 양성/HER2 음성 전이성 유방암 환자 220명에서 풀베스트란트에 팔보시클립을 추가해도 무진행생존기간이 개선되지 않았습니다(중앙값 4.6개월 대 4.8개월, HR 1.11, 90% CI 0.79–1.55). 풀베스트란트/팔보시클립/아벨루맙군의 무진행생존기간 중앙값은 8.1개월이었으나 풀베스트란트 단독과의 비교 결과는 결론을 내리기 어려웠고(HR 0.75, 90% CI 0.50–1.12), 초록에는 이상반응 자료가 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "confidence interval includes no effect", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PALMIRA", "trial": "B-PALMIRA", "papers": [ { "key": "P-PALMIRA", "pmid": "40294349", "title": "Second-Line Endocrine Therapy With or Without Palbociclib Rechallenge in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: PALMIRA Trial.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40294349/", "doi": "10.1200/JCO-24-01865", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Open-label phase II trial enriched for prior clinical benefit from a palbociclib-containing regimen, apart from the specified adjuvant eligibility route. Prior benefit does not demonstrate continued benefit after progression. The nonsignificant result is not equivalence or evidence that switching to a different CDK inhibitor cannot work. Treatment-emergent events are not all necessarily treatment-related. The exact safety-analysis denominators are not stated in the saved abstract and must not be inferred from randomized counts. Overall survival benefit is not established by this abstract.", "label": "PALMIRA · palbociclib rechallenge with a different endocrine therapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Palbociclib rechallenge plus second-line endocrine therapy versus second-line endocrine therapy alone", "population": "HR-positive, HER2-negative advanced breast cancer progressing after first-line palbociclib-based endocrine therapy with prior clinical benefit, or progressing on an adjuvant palbociclib-based regimen", "claim": "Among 198 randomized patients, median investigator-assessed PFS was 4.9 months with palbociclib rechallenge plus endocrine therapy versus 3.6 months with endocrine therapy alone (HR 0.84, 95% CI 0.66–1.07; P=.149). Grade ≥3 treatment-emergent adverse events occurred in 47.4% versus 10.0%. The primary PFS comparison did not demonstrate a significant benefit.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-PALMIRA", "nct": "NCT03809988", "acronym": "PALMIRA", "title": "PALbociclib Rechallenge in horMone Receptor-posItive/HER2- Negative Advanced Breast Cancer (PALMIRA)", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 198, "sponsor": "MedSIR", "sponsorClass": "OTHER", "collaborators": [ "Pfizer" ], "hasResults": false, "start": "2019-04-05", "lastUpdate": "2023-09-07", "url": "https://clinicaltrials.gov/study/NCT03809988" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS)", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "open-label", "n_randomized": 198, "assessment": "investigator", "quote": "This international, randomized, open-label, phase II study enrolled 198 patients with hormone receptor-positive/HER2-negative ABC with disease progression after first-line palbociclib plus ET (aromatase inhibitor or fulvestrant). … Patients were randomly assigned (2:1 ratio) to either palbociclib rechallenge plus second-line ET (fulvestrant or letrozole) or second-line ET alone. … The primary end point was investigator-assessed progression-free survival (PFS)." }, "effect": { "measure": "HR", "value": 0.84, "ci_low": 0.66, "ci_high": 1.07, "ci_level": "95%", "p": ".149", "endpoint": "Investigator-assessed PFS", "quote": "Median investigator-assessed PFS was 4.9 months (95% CI, 3.6 to 6.1) with palbociclib plus ET versus 3.6 months (95% CI, 2.5 to 4.2) with ET alone (hazard ratio, 0.84 [95% CI, 0.66 to 1.07]; P = .149)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 47.4, "grade3plus_control_pct": 10, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade ≥3 treatment-emergent adverse events were higher with palbociclib plus ET (47.4% v 10.0%), without new safety signals." }, "takeaway_en": "In patients with HR-positive, HER2-negative advanced breast cancer progressing after first-line palbociclib plus endocrine therapy, palbociclib rechallenge with a different endocrine therapy was compared with second-line endocrine therapy alone. Median investigator-assessed PFS was 4.9 versus 3.6 months (HR 0.84, 95% CI 0.66–1.07; P = .149), not a significant difference, while grade ≥3 treatment-emergent adverse events were more frequent with rechallenge (47.4% vs 10.0%).", "takeaway_ko": "1차 팔보시클립 병용 내분비요법 후 진행한 호르몬수용체 양성, HER2 음성 진행성 유방암 환자에서, 다른 내분비요법과 함께 팔보시클립을 재투여하는 치료를 2차 내분비요법 단독과 비교했습니다. 연구자 평가 무진행생존기간 중앙값은 4.9개월 대 3.6개월(위험비 0.84, 95% 신뢰구간 0.66–1.07; P = .149)로 유의한 차이가 없었으며, 3등급 이상 치료 관련 이상반응은 팔보시클립 재투여군에서 더 많았습니다(47.4% 대 10.0%).", "certainty": { "level": "very low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "confidence interval includes no effect", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DYNAMIC3", "trial": null, "papers": [ { "key": "P-DYNAMIC3", "pmid": "41115959", "title": "Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41115959/", "doi": "10.1038/s41591-025-04030-w", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The study compares management strategies, not the diagnostic result itself. The ctDNA-negative and ctDNA-positive groups have different primary RFS time horizons. Reduced exposure and hospitalizations do not establish noninferior recurrence outcomes, and strong prognostic separation does not prove that chemotherapy escalation improves outcomes. The abstract does not state the numerical noninferiority margin or confidence interval for the between-strategy RFS difference. Stage III findings must not be replaced with those of the separate stage II DYNAMIC trial. Negative ctDNA is not proof of eradication; this ANZCTR registration is separate from the ClinicalTrials.gov count.", "label": "DYNAMIC-III · ctDNA-guided stage III colon adjuvant strategy", "registry": { "system": "ANZCTR", "id": "ACTRN12617001566325", "url": "https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617001566325" }, "program": "colorectal", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Postoperative ctDNA-guided adjuvant de-escalation for ctDNA-negative patients or escalation for ctDNA-positive patients, versus standard management", "population": "Resected stage III colon cancer with postoperative ctDNA testing before adjuvant management", "claim": "Among 968 evaluable patients, 702 (72.5%) were ctDNA negative. In that group, de-escalation reduced oxaliplatin use (34.8% versus 88.6%) and treatment-related hospitalizations (8.5% versus 13.2%), but 3-year RFS was 85.3% versus 88.1% and the noninferiority margin was not met. In ctDNA-positive patients, escalation did not improve outcomes: 2-year RFS was 51% versus 61% with standard management.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-JACCROGC07", "trial": null, "papers": [ { "key": "P-JACCROGC07", "pmid": "37548812", "title": "Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study.", "journal": "Gastric Cancer", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37548812/", "doi": "10.1007/s10120-023-01419-9", "errata": [ { "pmid": "38867085", "title": "Correction: Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study.", "url": "https://pubmed.ncbi.nlm.nih.gov/38867085/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The final report follows the same trial population; it is not independent replication. Overall survival was secondary to the primary relapse-free survival endpoint. Better survival does not imply elimination of late recurrence or superiority to untested regimens. A publisher correction replaces incorrectly described recurrence counts with event counts; the erroneous counts are not used here. The saved abstract does not quantify toxicity. UMIN registration is separate from the ClinicalTrials.gov count.", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "JACCRO GC-07 · adjuvant S-1 plus docetaxel", "registry": { "system": "UMIN-CTR", "id": "UMIN000010337", "url": "https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012099" }, "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Postoperative S-1 plus docetaxel versus S-1 alone after gastrectomy with D2 lymphadenectomy", "population": "Pathologically confirmed stage III gastric cancer", "claim": "The final report analyzed 912 patients. For the primary endpoint, 3-year relapse-free survival was 67.7% versus 57.4% (HR 0.715, 95% CI 0.587–0.871; p=0.0008). At 5 years, overall survival was 67.91% versus 60.27% (HR 0.752, 95% CI 0.613–0.922; p=0.0059). Rates of late recurrence beyond 3 years were similar: 7.3% versus 7.2%.", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "3-year relapse-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer … Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed.", "quote_note": "912 is the analyzed population; the number randomized is not stated" }, "effect": { "measure": "HR", "value": 0.715, "ci_low": 0.587, "ci_high": 0.871, "ci_level": "95%", "p": "0.0008", "endpoint": "3-year relapse-free survival", "quote": "clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008)" }, "landmark": [ { "endpoint": "Relapse-free survival", "timepoint": "3 years", "experimental_pct": 67.7, "control_pct": 57.4, "higher_is_better": true, "experimental_arm": "S-1 plus docetaxel", "control_arm": "S-1 alone", "quote": "3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008)", "difference_pp": 10.3, "nnt": 10, "quote_note": "primary result from the previous report, as restated in the 2023 final report" }, { "endpoint": "Overall survival", "timepoint": "5 years", "experimental_pct": 67.91, "control_pct": 60.27, "higher_is_better": true, "experimental_arm": "S-1 plus docetaxel", "control_arm": "S-1 alone", "quote": "Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613-0.922; p = 0.0059).", "difference_pp": 7.6, "nnt": 14, "quote_note": "2023 final report" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In patients with pathologically stage III gastric cancer after gastrectomy with D2 lymphadenectomy, adjuvant S-1 plus docetaxel was compared with S-1 alone. Three-year relapse-free survival was 67.7% versus 57.4%, and five-year overall survival was 67.91% versus 60.27%; late recurrence beyond 3 years was similar (7.3% versus 7.2%), and this abstract reports no toxicity data, so the harm trade-off cannot be assessed from it.", "takeaway_ko": "D2 림프절 절제술을 동반한 위절제술 후 병리학적 3기 위암 환자에서 보조요법으로 S-1+도세탁셀 병용과 S-1 단독을 비교하였다. 3년 무재발생존율은 67.7% 대 57.4%, 5년 전체생존율은 67.91% 대 60.27%였고 3년 이후 후기 재발률은 7.3% 대 7.2%로 비슷했으며, 이 초록에는 독성 자료가 보고되지 않아 위해 측면의 득실은 판단할 수 없다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-GALAXY", "trial": null, "papers": [ { "key": "P-GALAXY", "pmid": "39284954", "title": "ctDNA-based molecular residual disease and survival in resectable colorectal cancer.", "journal": "Nat Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39284954/", "doi": "10.1038/s41591-024-03254-6", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Treatment was not randomized, so chemotherapy-associated outcomes do not establish a causal treatment benefit. Residual-disease and serial-clearance analyses use subsets of the reported cohort. CtDNA clearance is a prognostic association, not a validated surrogate for survival or proof of eradication. The expanded analysis overlaps the earlier GALAXY report and remains one evidence unit. The abstract and full text differ in their stage descriptions, so the population is not restricted here to a particular stage. UMIN registration is separate from the ClinicalTrials.gov count.", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "GALAXY · ctDNA residual disease and postoperative prognosis", "registry": { "system": "UMIN-CTR", "id": "UMIN000039205", "url": "https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000044197" }, "program": "colorectal", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Prospective observational ctDNA monitoring following curative-intent colorectal cancer resection", "population": "Resected colorectal cancer in the expanded GALAXY cohort", "claim": "The updated report included 2,240 patients with median follow-up of 23 months. In the molecular residual disease window, ctDNA positivity was associated with worse disease-free survival (HR 11.99; P<0.0001) and overall survival (HR 9.68; P<0.0001).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-SOFT", "trial": "B-SOFT", "papers": [ { "key": "P-SOFT", "pmid": "25495490", "title": "Adjuvant ovarian suppression in premenopausal breast cancer.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25495490/", "doi": "10.1056/NEJMoa1412379", "errata": [] }, { "key": "P-SOFT2026", "pmid": "42229584", "title": "Final outcomes of the SOFT and TEXT phase III trials in premenopausal hormone receptor-positive early breast cancer.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42229584/", "doi": "10.1016/j.annonc.2026.05.704", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [], "limits": "DFS and breast cancer-free interval are different endpoints; the later recurrence result does not change the original primary result. Survival differences in selected high-risk subgroups cannot be generalized to all participants. This unit uses SOFT-specific results only. The final publication also pools SOFT with TEXT, but that pooled comparison is not a second independent SOFT result or a TEXT-only estimate. Neither saved abstract supplies quantitative toxicity rates; ovarian suppression should not be described as harmless.", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "SOFT · ovarian suppression in premenopausal early breast cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Adjuvant tamoxifen alone, tamoxifen plus ovarian function suppression, or exemestane plus ovarian function suppression", "population": "Premenopausal women with hormone receptor-positive early breast cancer; with or without prior chemotherapy", "claim": "The original trial randomized 3066 women. In its primary comparison, tamoxifen plus ovarian suppression did not significantly improve 5-year DFS over tamoxifen alone: 86.6% versus 84.7% (HR 0.83, 95% CI 0.66–1.04; P=0.10). The final report included 3047 SOFT patients in its intention-to-treat population. At 15 years, the breast cancer-free interval was 78.6% with exemestane plus suppression, 75.7% with tamoxifen plus suppression and 72.1% with tamoxifen; the HR for tamoxifen plus suppression versus tamoxifen was 0.82 (95% CI 0.69–0.98; P=0.03).", "trialRecord": { "key": "B-SOFT", "nct": "NCT00066690", "acronym": "SOFT", "title": "Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 3066, "sponsor": "ETOP IBCSG Partners Foundation", "sponsorClass": "NETWORK", "collaborators": [ "Breast International Group", "Cancer and Leukemia Group B", "National Cancer Institute (NCI)", "NSABP Foundation Inc", "NCIC Clinical Trials Group", "North Central Cancer Treatment Group", "SWOG Cancer Research Network" ], "hasResults": true, "start": "2003-12-17", "lastUpdate": "2026-08-26", "url": "https://clinicaltrials.gov/study/NCT00066690" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (disease recurrence, second invasive cancer, or death), tamoxifen plus ovarian suppression versus tamoxifen alone", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 3066, "assessment": "not stated", "quote": "We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. … Final outcomes of the SOFT and TEXT phase III trials in premenopausal hormone receptor-positive early breast cancer." }, "effect": { "measure": "HR", "value": 0.83, "ci_low": 0.66, "ci_high": 1.04, "ci_level": "95%", "p": "0.10", "endpoint": "Disease-free survival, tamoxifen plus ovarian suppression vs tamoxifen alone (primary analysis, median follow-up 67 months)", "quote": "After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10)." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "5 years", "experimental_pct": 86.6, "control_pct": 84.7, "higher_is_better": true, "experimental_arm": "Tamoxifen plus ovarian suppression", "control_arm": "Tamoxifen alone", "quote": "the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group", "difference_pp": 1.9, "nnt": 53, "quote_note": "P-SOFT 2015, primary analysis; DFS not reported at 15 years in the final paper" }, { "endpoint": "Breast cancer-free interval", "timepoint": "15 years", "experimental_pct": 75.7, "control_pct": 72.1, "higher_is_better": true, "experimental_arm": "Tamoxifen plus ovarian suppression", "control_arm": "Tamoxifen alone", "quote": "In SOFT, escalating endocrine therapy (ET) continued to reduce recurrence with 15-year BCFI of 78.6% for E+OFS, 75.7% for T+OFS, and 72.1% for T (T+OFS versus T: HR 0.82, 95% CI, 0.69-0.98, P = 0.03).", "difference_pp": 3.6, "nnt": 28, "quote_note": "P-SOFT2026, final 15-year report" }, { "endpoint": "Breast cancer-free interval", "timepoint": "15 years", "experimental_pct": 78.6, "control_pct": 72.1, "higher_is_better": true, "experimental_arm": "Exemestane plus ovarian suppression", "control_arm": "Tamoxifen alone", "quote": "In SOFT, escalating endocrine therapy (ET) continued to reduce recurrence with 15-year BCFI of 78.6% for E+OFS, 75.7% for T+OFS, and 72.1% for T", "difference_pp": 6.5, "nnt": 16, "quote_note": "P-SOFT2026, final 15-year report" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In premenopausal women with hormone receptor-positive early breast cancer, adding ovarian suppression to 5 years of tamoxifen did not significantly improve 5-year disease-free survival (86.6% vs 84.7%; HR 0.83, 95% CI 0.66–1.04). At 15 years, the breast cancer-free interval was 78.6% with exemestane plus suppression, 75.7% with tamoxifen plus suppression and 72.1% with tamoxifen alone (tamoxifen plus suppression vs tamoxifen HR 0.82); neither abstract reports adverse event rates, so the harm trade-off cannot be judged from these sources.", "takeaway_ko": "호르몬 수용체 양성 조기 유방암 폐경 전 여성에서 5년간 타목시펜에 난소기능억제를 추가해도 5년 무병생존율이 유의하게 개선되지 않았습니다(86.6% 대 84.7%; HR 0.83, 95% CI 0.66–1.04). 15년 유방암 무발생 기간은 엑세메스탄+난소기능억제군 78.6%, 타목시펜+난소기능억제군 75.7%, 타목시펜 단독군 72.1%였습니다(타목시펜+난소기능억제 대 타목시펜 HR 0.82). 두 초록 모두 이상반응 발생률을 보고하지 않아 이 자료만으로는 위해와의 득실을 판단할 수 없습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ExteNET", "trial": "B-ExteNET", "papers": [ { "key": "P-ExteNET", "pmid": "26874901", "title": "Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26874901/", "doi": "10.1016/S1470-2045(15)00551-3", "errata": [] }, { "key": "P-ExteNET5y", "pmid": "29146401", "title": "Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/29146401/", "doi": "10.1016/S1470-2045(17)30717-9", "errata": [] }, { "key": "P-ExteNETOS", "pmid": "36898233", "title": "Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Eur J Cancer", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36898233/", "doi": "10.1016/j.ejca.2023.02.002", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The IDFS and final survival findings are different endpoints in one trial, not independent replications. Both hormone-receptor groups were enrolled; these overall estimates must not be relabeled as a hormone-receptor-positive subgroup result. An overall survival benefit was not demonstrated, which is not proof of equivalence. Eligibility changed during recruitment. These abstracts do not establish effects after every contemporary HER2 regimen, nor does the trial test selecting treatment solely by residual disease after neoadjuvant therapy. Safety-analysis denominators must not be inferred from randomized counts.", "label": "ExteNET · extended neratinib after trastuzumab", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "One year of neratinib versus placebo after chemotherapy and trastuzumab-based therapy", "population": "HER2-positive early breast cancer without recurrence at entry; eligibility was amended from stage I–III to stage II–III and from trastuzumab completion within two years to within one year", "claim": "Among 2840 randomized women, 2-year invasive disease-free survival (IDFS) was 93.9% versus 91.6% (HR 0.67, 95% CI 0.50–0.91; P=.0091). The protocol-defined 5-year sensitivity analysis reported IDFS of 90.2% versus 87.7% (HR 0.73, 95% CI 0.57–0.92; P=.0083). Final 8-year overall survival was 90.1% versus 90.2% (HR 0.95, 95% CI 0.75–1.21; P=.6914). Without diarrhea prophylaxis, grade 3 diarrhea occurred in 40% versus 2%, and grade 4 diarrhea in less than 1% of the neratinib group.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ExteNET", "nct": "NCT00878709", "acronym": "ExteNET", "title": "Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 2840, "sponsor": "Puma Biotechnology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2009-07-09", "lastUpdate": "2021-06-11", "url": "https://clinicaltrials.gov/study/NCT00878709" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival at 2 years after randomisation (as defined in the original protocol)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 2840, "assessment": "not stated", "quote": "We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America … Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420)." }, "effect": { "measure": "HR", "value": 0.67, "ci_low": 0.5, "ci_high": 0.91, "ci_level": "95%", "p": "0.0091", "endpoint": "2-year invasive disease-free survival (primary analysis)", "quote": "At 2 year follow-up, 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091)." }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "5 years", "experimental_pct": 90.2, "control_pct": 87.7, "higher_is_better": true, "experimental_arm": "Neratinib 240 mg/day for 1 year", "control_arm": "Placebo", "quote": "The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group.", "difference_pp": 2.5, "nnt": 40, "quote_note": "5-year sensitivity analysis, P-ExteNET5y 2017; supersedes the 2-year figures of 93·9% vs 91·6%" }, { "endpoint": "Overall survival", "timepoint": "8 years", "experimental_pct": 90.1, "control_pct": 90.2, "higher_is_better": true, "experimental_arm": "Neratinib 240 mg/day for 1 year", "control_arm": "Placebo", "quote": "Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 0.6914).", "difference_pp": -0.1, "nnt": null, "nnt_label": "favours control", "quote_note": "final OS analysis, P-ExteNETOS 2023", "nnh": 1000 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "None of the deaths were attributed to study treatment in either group.", "quote": "Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [<1%] grade 4 with neratinib vs 23 [2%] grade 3 with placebo), vomiting (grade 3: 47 [3%] vs five [<1%]), and nausea (grade 3: 26 [2%] vs two [<1%]). Treatment-emergent serious adverse events occurred in 103 (7%) women in the neratinib group and 85 (6%) women in the placebo group." }, "takeaway_en": "In women with HER2-positive early breast cancer who had completed chemotherapy plus trastuzumab, the trial compared one year of neratinib with placebo. At 5 years, invasive disease-free survival was 90.2% with neratinib versus 87.7% with placebo, but 8-year overall survival was 90.1% versus 90.2%, and grade 3 diarrhea occurred in 40% versus 2% of patients when no diarrhea prophylaxis was used.", "takeaway_ko": "항암화학요법과 트라스투주맙 치료를 마친 HER2 양성 조기 유방암 여성에서, 이 시험은 1년간의 네라티닙 투여를 위약과 비교했습니다. 5년 무침습질환생존율은 네라티닙군 90.2%, 위약군 87.7%였으나 8년 전체생존율은 각각 90.1%와 90.2%였고, 설사 예방요법 없이 3등급 설사가 네라티닙군 40%, 위약군 2%에서 발생했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KAITLIN", "trial": "B-KAITLIN", "papers": [ { "key": "P-KAITLIN", "pmid": "34890214", "title": "Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/34890214/", "doi": "10.1200/JCO.21.00896", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Coprimary IDFS endpoints used hierarchical testing, first in node-positive patients. Nonsignificance does not establish equivalence. Patients were not selected for residual invasive disease after neoadjuvant therapy, unlike KATHERINE. Completion and adverse-event differences do not establish superior net benefit, and overall survival benefit is not established by the saved abstract. Safety-analysis denominators are not given in the saved abstract and must not be inferred from randomized counts.", "label": "KAITLIN · postoperative HER2 regimen substitution", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "After surgery and anthracycline chemotherapy: T-DM1 plus pertuzumab versus taxane plus trastuzumab and pertuzumab", "population": "Excised HER2-positive early breast cancer, node-positive or node-negative with hormone-receptor-negative disease and tumor >2 cm", "claim": "Among 1846 participants, invasive disease-free survival (IDFS) did not improve in the node-positive population (HR 0.97, 95% CI 0.71–1.32) or the overall population (HR 0.98, 95% CI 0.72–1.32). Overall 3-year IDFS was 93.1% with T-DM1/pertuzumab versus 94.2% with taxane/trastuzumab/pertuzumab. The assigned 18 cycles of T-DM1 or trastuzumab were completed by 65.0% versus 88.4%; grade ≥3 adverse events occurred in 51.8% versus 55.4%.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-KAITLIN", "nct": "NCT01966471", "acronym": null, "title": "A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 1846, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-01-31", "lastUpdate": "2022-06-14", "url": "https://clinicaltrials.gov/study/NCT01966471" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations (coprimary, hierarchical testing)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 1846, "assessment": "not stated", "quote": "The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). … overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32)" }, "effect": { "measure": "HR", "value": 0.97, "ci_low": 0.71, "ci_high": 1.32, "ci_level": "95%", "p": null, "endpoint": "IDFS, node-positive population (first coprimary endpoint); overall population stratified HR 0.98 (95% CI 0.72 to 1.32)", "quote": "There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32)." }, "landmark": [ { "endpoint": "Invasive disease-free survival (overall population)", "timepoint": "3 years", "experimental_pct": 93.1, "control_pct": 94.2, "higher_is_better": true, "experimental_arm": "AC-KP (anthracycline then T-DM1 plus pertuzumab)", "control_arm": "AC-THP (anthracycline then taxane plus trastuzumab plus pertuzumab)", "quote": "In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP.", "difference_pp": -1.1, "nnt": null, "nnt_label": "favours control", "quote_note": "J Clin Oncol 2022; median follow-up 57.0-57.1 months", "nnh": 91 } ], "harms": { "grade3plus_experimental_pct": 51.8, "grade3plus_control_pct": 55.4, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively." }, "takeaway_en": "In 1846 patients with resected high-risk HER2-positive early breast cancer who received anthracycline chemotherapy after surgery, replacing taxane plus trastuzumab with T-DM1 (trastuzumab emtansine; both arms with pertuzumab) did not improve invasive disease-free survival: 3-year IDFS was 93.1% with T-DM1/pertuzumab versus 94.2% with taxane/trastuzumab/pertuzumab (node-positive HR 0.97, 95% CI 0.71 to 1.32). Grade ≥3 adverse events were similar (51.8% vs 55.4%), but fewer patients completed all 18 cycles with T-DM1 (65.0% vs 88.4%), mainly because of T-DM1 discontinuation for laboratory abnormalities (12.5%).", "takeaway_ko": "수술 후 안트라사이클린 항암화학요법을 받은 고위험 HER2 양성 조기 유방암 환자 1846명에서, 탁산과 트라스투주맙을 T-DM1(트라스투주맙 엠탄신)으로 대체해도(양군 모두 퍼투주맙 병용) 침습적 무질병 생존율은 개선되지 않았습니다. 3년 IDFS는 T-DM1/퍼투주맙군 93.1%, 탁산/트라스투주맙/퍼투주맙군 94.2%였습니다(림프절 양성 위험비 0.97, 95% 신뢰구간 0.71–1.32). 3등급 이상 이상반응은 비슷했으나(51.8% 대 55.4%), 18주기를 모두 완료한 비율은 T-DM1군에서 더 낮았습니다(65.0% 대 88.4%). 이는 주로 검사실 수치 이상으로 인한 T-DM1 중단(12.5%) 때문이었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code; English takeaway aligned with the Korean and the abstract by Claude Opus 5.5, 2026-11-07" } }, { "id": "U-NSABPB42", "trial": "B-NSABPB42", "papers": [ { "key": "P-NSABPB42", "pmid": "30509771", "title": "Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30509771/", "doi": "10.1016/S1470-2045(18)30621-1", "errata": [ { "pmid": "30614468", "title": "Correction to Lancet Oncol 2019; 20: 88-99.", "url": "https://pubmed.ncbi.nlm.nih.gov/30614468/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-NSABPB42-10y", "pmid": "37184928", "title": "Ten-year update: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial: extended letrozole therapy in early-stage breast cancer.", "journal": "J Natl Cancer Inst", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37184928/", "doi": "10.1093/jnci/djad078", "errata": [ { "pmid": "37766422", "title": "Correction to: Ten-year update: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial: extended letrozole therapy in early-stage breast cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/37766422/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [], "limits": "DFS includes recurrence, second primary malignancy, or death; it is not recurrence alone. The later analysis updates the same trial and does not retroactively make the initial primary analysis positive. The full report states that the 10-year update was not prespecified in the protocol. Follow-up availability and exclusions differ by endpoint; the randomized count must not be substituted for every analysis denominator. Reported absence of differences in fractures and arterial events does not establish equivalence or absence of harm. HER2-negative status is not imposed on this HR-positive trial.", "label": "NSABP B-42 · extended letrozole with long-term follow-up", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Five additional years of letrozole versus placebo after approximately five years of aromatase-inhibitor-based endocrine therapy", "population": "Postmenopausal women with stage I–IIIA hormone-receptor-positive breast cancer, disease-free after an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor", "claim": "In the initial analysis of 3966 randomized patients, at a median follow-up of 6.9 years, DFS did not meet the adjusted significance threshold of .0418 (HR 0.85, 95% CI 0.73–0.999; P=.048). At a median follow-up of 10.3 years, 10-year DFS was 75.9% versus 72.6% (HR 0.85, 95% CI 0.74–0.96; P=.01). Overall survival was not improved (HR 0.97, 95% CI 0.82–1.15; P=.74); distant recurrence was lower (HR 0.72, 95% CI 0.55–0.92; P=.01).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-NSABPB42", "nct": "NCT00382070", "acronym": null, "title": "Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 3966, "sponsor": "NSABP Foundation Inc", "sponsorClass": "NETWORK", "collaborators": [ "National Cancer Institute (NCI)", "Novartis" ], "hasResults": true, "start": "2006-08", "lastUpdate": "2024-03-22", "url": "https://clinicaltrials.gov/study/NCT00382070" }, "sources": 3, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival, defined as time from randomisation to breast cancer recurrence, second primary malignancy, or death", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 3966, "assessment": "not stated", "quote": "This randomised, double-blind, placebo-controlled, phase 3 trial was done in 158 centres in the USA, Canada, and Ireland. … Between Sept 28, 2006, and Jan 6, 2010, 3966 patients were randomly assigned to receive letrozole (n=1983) or placebo (n=1983)." }, "effect": { "measure": "HR", "value": 0.85, "ci_low": 0.74, "ci_high": 0.96, "ci_level": "95%", "p": "P = .01", "endpoint": "Disease-free survival (10-year update, median follow-up 10.3 years)", "quote": "There was statistically significant improvement in DFS in favor of letrozole compared with placebo (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.74 to 0.96; P = .01; 10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference = 3.3%)." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "10 years", "experimental_pct": 75.9, "control_pct": 72.6, "higher_is_better": true, "experimental_arm": "Letrozole 2.5 mg daily for 5 years", "control_arm": "Placebo", "quote": "10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference = 3.3%", "difference_pp": 3.3, "nnt": 31, "quote_note": "From the 2023 10-year update (median follow-up 10.3 years), which supersedes the 2019 7-year estimates" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common grade 3 adverse events were arthralgia (47 [2%] of 1933 patients in the placebo group vs 50 [3%] of 1941 patients in the letrozole group) and back pain (44 [2%] vs 38 [2%]). … The rates of osteoporotic fractures and arterial thrombotic events did not differ between treatment groups." }, "takeaway_en": "In 3966 postmenopausal women with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after about 5 years of aromatase inhibitor-based therapy, 5 more years of letrozole versus placebo gave 10-year disease-free survival of 75.9% versus 72.6% (absolute difference 3.3%; HR 0.85), although the earlier 6.9-year analysis had missed its significance threshold and overall survival was not improved (HR 0.97). Reported grade 3 toxicity was low, with arthralgia in 3% versus 2% and back pain in 2% in each arm, and osteoporotic fracture and arterial thrombotic event rates did not differ between groups.", "takeaway_ko": "약 5년간 아로마타제 억제제 기반 치료 후 무병 상태인 1–3A기 호르몬 수용체 양성 폐경 후 유방암 환자 3966명에서 레트로졸 5년 추가 투여를 위약과 비교한 결과, 10년 무병생존율은 75.9% 대 72.6%였습니다(절대 차이 3.3%, 위험비 0.85). 다만 앞선 6.9년 분석에서는 유의성 기준을 충족하지 못했고, 전체 생존은 개선되지 않았습니다(위험비 0.97). 보고된 3등급 독성은 낮았으며, 관절통은 3% 대 2%, 요통은 양군 모두 2%였고, 골다공증성 골절과 동맥 혈전 사건의 발생률은 두 군 간에 차이가 없었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ASTRRA", "trial": "B-ASTRRA", "papers": [ { "key": "P-ASTRRA", "pmid": "31518174", "title": "Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.", "journal": "J Clin Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31518174/", "doi": "10.1200/JCO.19.00126", "errata": [] }, { "key": "P-ASTRRA8y", "pmid": "37607321", "title": "Adding Ovarian Suppression to Tamoxifen for Premenopausal Women With Hormone Receptor-Positive Breast Cancer After Chemotherapy: An 8-Year Follow-Up of the ASTRRA Trial.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37607321/", "doi": "10.1200/JCO.23.00557", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-HR" ], "subtypes": [], "limits": "The follow-up concerns the same trial. Eligibility depended on post-chemotherapy ovarian function, not young age alone. The earlier overall-survival result cannot replace the nonsignificant later comparison. This does not compare two versus five years of ovarian suppression, an aromatase-inhibitor regimen, or endocrine extension after five disease-free years. Saved abstracts do not quantify adverse events. HER2-negative status is not assumed for the whole ER-positive population.", "label": "ASTRRA · ovarian suppression after chemotherapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Five years of tamoxifen with two years of ovarian-function suppression versus five years of tamoxifen alone after chemotherapy", "population": "Young women with estrogen-receptor-positive breast cancer treated with definitive surgery and chemotherapy who remained premenopausal or recovered ovarian function", "claim": "The primary report counted 1483 women enrolled, 1293 randomized and 1282 eligible for analysis. Five-year DFS was 91.1% with ovarian suppression plus tamoxifen versus 87.5% with tamoxifen alone (HR 0.69, 95% CI 0.48–0.97; P=.033). At a median follow-up of 106.4 months, 8-year DFS was 85.4% versus 80.2% (HR 0.67, 95% CI 0.51–0.87). Eight-year overall survival was 96.5% versus 95.3% (HR 0.78, 95% CI 0.49–1.25), without a significant difference.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ASTRRA", "nct": "NCT00912548", "acronym": "ASTRRA", "title": "Evaluating the Role of the Addition of Ovarian Function Suppression (OFS) to Tamoxifen in Young Women", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 1234, "sponsor": "Korean Breast Cancer Study Group", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2009-05", "lastUpdate": "2009-06-16", "url": "https://clinicaltrials.gov/study/NCT00912548" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (DFS), defined from the time of enrollment to the time of the first event", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. … A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis.", "quote_note": "P-ASTRRA, J Clin Oncol 2020: A Randomized Phase III Trial" }, "effect": { "measure": "HR", "value": 0.67, "ci_low": 0.51, "ci_high": 0.87, "ci_level": "95%", "p": null, "endpoint": "DFS at 106.4 months median follow-up (8-year update)", "quote": "At 106.4 months of median follow-up, there was a continuous significant reduction in the DFS event rate in the TAM + OFS group. The 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (hazard ratio [HR], 0.67; 95% CI, 0.51 to 0.87).", "quote_note": "P-ASTRRA8y, 2023 update; primary report: HR 0.69, 95% CI 0.48 to 0.97, P = .033" }, "landmark": [ { "endpoint": "DFS", "timepoint": "8 years", "experimental_pct": 85.4, "control_pct": 80.2, "higher_is_better": true, "experimental_arm": "Tamoxifen 5 years + ovarian function suppression (monthly goserelin) for 2 years", "control_arm": "Tamoxifen 5 years alone", "quote": "The 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (hazard ratio [HR], 0.67; 95% CI, 0.51 to 0.87).", "difference_pp": 5.2, "nnt": 20, "quote_note": "Most recent paper, P-ASTRRA8y, 106.4 months median follow-up; supersedes the 5-year DFS of 91.1% vs 87.5% in P-ASTRRA" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In women aged 45 or younger with estrogen-receptor-positive breast cancer who remained premenopausal or regained ovarian function after chemotherapy, adding 2 years of goserelin ovarian suppression to 5 years of tamoxifen raised 8-year disease-free survival to 85.4% from 80.2% with tamoxifen alone (HR 0.67); at the updated follow-up, overall survival did not differ significantly (96.5% vs 95.3%, HR 0.78, 95% CI 0.49 to 1.25). Neither abstract reports adverse events, so the harm trade-off of added ovarian suppression cannot be judged from these sources.", "takeaway_ko": "항암화학요법 후에도 폐경 전 상태를 유지하거나 난소 기능이 회복된 45세 이하 에스트로겐 수용체 양성 유방암 환자에서, 타목시펜 5년 치료에 고세렐린을 이용한 난소기능억제 2년을 추가하자 8년 무병생존율이 타목시펜 단독군의 80.2%에서 85.4%로 높아졌습니다(위험비 0.67). 장기 추적 결과 전체생존율은 유의한 차이가 없었습니다(96.5% 대 95.3%, 위험비 0.78, 95% 신뢰구간 0.49–1.25). 두 초록 모두 이상반응을 보고하지 않아, 난소기능억제 추가에 따른 부작용 득실은 이 자료만으로 판단할 수 없습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ATLAS", "trial": "B-ATLAS", "papers": [ { "key": "P-ATLAS", "pmid": "23219286", "title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.", "journal": "Lancet", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23219286/", "doi": "10.1016/S0140-6736(12)61963-1", "errata": [ { "pmid": null, "title": "Lancet. 2013 Mar 9;381(9869):804", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60252-4/fulltext", "reviewed": true, "unresolvedIdentifier": true }, { "pmid": "28457627", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/28457627/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-HR" ], "subtypes": [], "limits": "This open-control extension trial is not a comparison with an aromatase inhibitor or ovarian suppression. Late benefit does not establish eradication, universal net benefit, or safety. Published corrections affect cardiac-event reporting, some mortality categories, appendix legends, and attribution. Those cardiac/mortality-category estimates and appendix subgroup curves are omitted; the reported ER-positive efficacy and selected harms are outside the stated correction scope. The separate center-exclusion letter has not been read in full, and underlying data were not audited here.", "label": "ATLAS · tamoxifen extension and late outcomes", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Continue tamoxifen to ten years versus stop after five years", "population": "Early breast cancer after five years of tamoxifen; efficacy estimates here concern ER-positive disease, while harm estimates concern all enrolled receptor groups", "claim": "In 6846 women with ER-positive disease, recurrence during years 5–14 was 21.4% with continuation versus 25.1% with stopping; breast-cancer mortality was 12.2% versus 15.0%. Across receptor groups, the incidence RR was 1.87 (95% CI 1.13–3.07) for pulmonary embolus and 1.74 (95% CI 1.30–2.34) for endometrial cancer.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ATLAS", "nct": "NCT00003016", "acronym": null, "title": "Prolonged Tamoxifen Compared With Shorter Tamoxifen in Treating Patients Who Have Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 20000, "sponsor": "University of Oxford", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "1995-10", "lastUpdate": "2009-02-09", "url": "https://clinicaltrials.gov/study/NCT00003016" }, "sources": 2, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": null, "primary_endpoint_type": null, "design": { "phase": null, "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": "0·002", "endpoint": "Breast cancer recurrence (ER-positive disease); no overall rate ratio reported. Period-specific recurrence RR was 0·90 (95% CI 0·79–1·02) during years 5–9 and 0·75 (0·62–0·90) in later years.", "quote": "Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002) … (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years" }, "landmark": [ { "endpoint": "Cumulative risk of breast cancer recurrence (ER-positive)", "timepoint": "years 5–14", "experimental_pct": 21.4, "control_pct": 25.1, "higher_is_better": false, "experimental_arm": "Continue tamoxifen to 10 years", "control_arm": "Stop tamoxifen at 5 years", "quote": "The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls", "difference_pp": -3.7, "nnt": 28, "quote_note": "single paper, Lancet 2013" }, { "endpoint": "Breast cancer mortality (ER-positive)", "timepoint": "years 5–14", "experimental_pct": 12.2, "control_pct": 15, "higher_is_better": false, "experimental_arm": "Continue tamoxifen to 10 years", "control_arm": "Stop tamoxifen at 5 years", "quote": "breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%)", "difference_pp": -2.8, "nnt": 36, "quote_note": "single paper, Lancet 2013" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Not reported as treatment-related deaths. Pulmonary embolus mortality was 0·2% in both groups. Endometrial cancer mortality was 0·4% with continuation versus 0·2% in controls (absolute mortality increase 0·2%).", "quote": "pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%)." }, "takeaway_en": "In women with ER-positive early breast cancer who had completed 5 years of tamoxifen, continuing to 10 years lowered the cumulative recurrence risk during years 5–14 to 21.4% versus 25.1% with stopping, and breast cancer mortality to 12.2% versus 15.0% (absolute reduction 2.8%). The trade-off, across all enrolled women, was more pulmonary embolus (RR 1.87) and endometrial cancer (3.1% vs 1.6% over years 5–14; absolute mortality increase 0.2%), while ischaemic heart disease was less frequent (RR 0.76).", "takeaway_ko": "타목시펜 5년 복용을 마친 에스트로겐 수용체(ER) 양성 조기 유방암 여성에서, 10년까지 복용을 지속하면 5~14년 사이 누적 재발 위험이 21.4%로 중단군의 25.1%보다 낮았습니다. 같은 기간 유방암 사망률도 12.2% 대 15.0%로 낮았습니다(절대 감소 2.8%). 반면 전체 등록 여성에서 폐색전증(RR 1.87)과 자궁내막암(5~14년 누적 3.1% 대 1.6%, 절대 사망률 증가 0.2%)이 증가했으며, 허혈성 심질환은 감소했습니다(RR 0.76).", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PRODIGY", "trial": "G-PRODIGY", "papers": [ { "key": "P-PRODIGY", "pmid": "34133211", "title": "PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34133211/", "doi": "10.1200/JCO.20.02914", "errata": [] }, { "key": "P-PRODIGYOS", "pmid": "38996201", "title": "Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer: Updated Overall Survival Outcomes From Phase III PRODIGY.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38996201/", "doi": "10.1200/JCO.23.02167", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The treated full-analysis set is smaller than the randomized population. The survival update follows the same patients and is not independent replication. Overall survival was secondary to PFS, and the updated abstract does not provide a confidence interval for the OS hazard ratio. Results compare against surgery plus adjuvant S-1 in this Korean population; they do not establish superiority over FLOT or other perioperative regimens. The reported fatal adverse events prevent interpreting the regimen as risk-free.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "PRODIGY · neoadjuvant DOS before D2 surgery", "result": "positive", "setting": "Neoadjuvant docetaxel, oxaliplatin and S-1 followed by D2 surgery and adjuvant S-1 versus surgery and adjuvant S-1", "population": "Korean patients with resectable locally advanced gastric or gastroesophageal junction adenocarcinoma", "claim": "The trial randomized 266 patients to the neoadjuvant strategy and 264 to surgery first; the treated full-analysis set contained 238 and 246 patients, respectively. The primary PFS analysis favored the neoadjuvant strategy (adjusted HR 0.70, 95% CI 0.52–0.95; P=.023). In the long-term update, overall survival, a secondary endpoint, also favored the neoadjuvant strategy (adjusted HR 0.72; P=.027); 8-year OS was 63.0% versus 55.1%. Two grade 5 adverse events occurred during neoadjuvant treatment.", "trialRecord": { "key": "G-PRODIGY", "nct": "NCT01515748", "acronym": "PRODIGY", "title": "Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 530, "sponsor": "Sanofi", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2011-12-30", "lastUpdate": "2023-12-13", "url": "https://clinicaltrials.gov/study/NCT01515748" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (PFS) with neoadjuvant DOS + D2 surgery + adjuvant S-1 (CSC) versus D2 surgery + adjuvant S-1 (SC)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set)." }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.52, "ci_high": 0.95, "ci_level": "95%", "p": "stratified log-rank P = .023", "endpoint": "PFS (primary analysis, adjusted HR)", "quote": "CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023)." }, "landmark": [ { "endpoint": "Overall survival (secondary endpoint)", "timepoint": "8 years", "experimental_pct": 63, "control_pct": 55.1, "higher_is_better": true, "experimental_arm": "Neoadjuvant DOS + D2 surgery + adjuvant S-1 (CSC)", "control_arm": "D2 surgery + adjuvant S-1 (SC)", "quote": "Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively.", "difference_pp": 7.9, "nnt": 13, "quote_note": "From the 2024 long-term update (median follow-up of surviving patients 99.5 months" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment; attribution to treatment not stated in the abstract.", "quote": "Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment." }, "takeaway_en": "In Korean patients with resectable locally advanced gastric or gastroesophageal junction adenocarcinoma (cT2-3N+ or T4Nany), adding three cycles of neoadjuvant docetaxel, oxaliplatin and S-1 before D2 surgery and adjuvant S-1 improved progression-free survival (HR 0.70) compared with surgery first. In the long-term update, 8-year overall survival was 63.0% versus 55.1%; grade 3 or higher toxicity rates were not reported in the abstracts, and two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment.", "takeaway_ko": "절제 가능한 국소진행성 위암 또는 위식도접합부 선암(cT2-3N+ 또는 T4Nany) 한국인 환자에서, D2 수술과 보조 S-1 요법 전에 도세탁셀·옥살리플라틴·S-1 선행항암화학요법 3주기를 추가한 군은 수술을 먼저 시행한 군보다 무진행생존을 개선했습니다(위험비 0.70). 장기 추적 결과 8년 전체생존율은 63.0% 대 55.1%였습니다. 초록에는 3등급 이상 이상반응 발생률이 보고되지 않았으며, 선행항암화학요법 중 5등급 이상반응(발열성 호중구감소증, 호흡곤란)이 2건 발생했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TOPGEAR", "trial": "G-TOPGEAR", "papers": [ { "key": "P-TOPGEAR", "pmid": "39282905", "title": "Preoperative Chemoradiotherapy for Resectable Gastric Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39282905/", "doi": "10.1056/NEJMoa2405195", "errata": [] }, { "key": "P-TOPGEAROLDER", "pmid": "42673704", "title": "Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.", "journal": "Eur J Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42673704/", "doi": "10.1016/j.ejca.2026.117005", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary overall-survival endpoint was not improved; a higher pathological complete response rate did not establish a survival benefit. The comparison used more than one chemotherapy backbone and does not isolate a FLOT-only treatment effect. The abstract gives no quantitative overall toxicity comparison. The later older-adult analysis is exploratory, compares age groups that were not randomized, and remains part of this same trial rather than independent replication. Registry status and estimated completion dates are not substitutes for the published endpoint results.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "TOPGEAR · preoperative chemoradiotherapy", "result": "negative", "setting": "Preoperative chemoradiotherapy plus perioperative chemotherapy versus perioperative chemotherapy alone", "population": "Resectable gastric or gastroesophageal junction adenocarcinoma in an international randomized trial", "claim": "Among 574 randomized patients, 286 were assigned to the chemoradiotherapy strategy and 288 to the chemotherapy strategy. Pathological complete response rates were 17% versus 8%, but median overall survival was 46 versus 49 months (death HR 1.05, 95% CI 0.83–1.31) at a median follow-up of 67 months. Median PFS was 31 versus 32 months. Treatment-related toxicity was described as similar between groups.", "trialRecord": { "key": "G-TOPGEAR", "nct": "NCT01924819", "acronym": "TOPGEAR", "title": "Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 574, "sponsor": "Australasian Gastro-Intestinal Trials Group", "sponsorClass": "NETWORK", "collaborators": [ "National Health and Medical Research Council, Australia", "Trans Tasman Radiation Oncology Group", "European Organisation for Research and Treatment of Cancer - EORTC", "NCIC Clinical Trials Group" ], "hasResults": false, "start": "2009-09", "lastUpdate": "2025-03-04", "url": "https://clinicaltrials.gov/study/NCT01924819" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 574, "assessment": "not stated", "quote": "We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control) … A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group." }, "effect": { "measure": "HR", "value": 1.05, "ci_low": 0.83, "ci_high": 1.31, "ci_level": "95%", "p": null, "endpoint": "Overall survival (death)", "quote": "The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31)" }, "landmark": [ { "endpoint": "Pathological complete response", "timepoint": "After resection", "experimental_pct": 17, "control_pct": 8, "higher_is_better": true, "experimental_arm": "Preoperative chemoradiotherapy plus perioperative chemotherapy", "control_arm": "Perioperative chemotherapy alone", "quote": "A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection.", "difference_pp": 9, "nnt": 12, "quote_note": "P-TOPGEAR (NEJM 2024, primary report" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Treatment-related toxic effects were similar in the two groups." }, "takeaway_en": "In 574 patients with resectable gastric or gastroesophageal junction adenocarcinoma, adding preoperative chemoradiotherapy (45 Gy in 25 fractions with fluorouracil) to perioperative chemotherapy raised pathological complete response from 8% to 17%, but did not improve overall survival (median 46 vs. 49 months; HR for death 1.05, 95% CI 0.83 to 1.31) at a median follow-up of 67 months. Treatment-related toxic effects were reported as similar in the two groups.", "takeaway_ko": "절제 가능한 위 또는 위식도접합부 선암 환자 574명에서 수술 전후 항암화학요법에 수술 전 항암화학방사선요법(45 Gy/25회, 플루오로우라실 병용)을 추가했을 때, 병리학적 완전관해율은 8%에서 17%로 높아졌습니다. 그러나 추적관찰 기간 중앙값 67개월 시점에 전체생존기간은 개선되지 않았습니다(중앙값 46개월 대 49개월, 사망 위험비 1.05, 95% 신뢰구간 0.83–1.31). 치료 관련 독성은 두 군 간에 비슷한 것으로 보고되었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ARTIST", "trial": "G-ARTIST", "papers": [ { "key": "P-ARTIST", "pmid": "22184384", "title": "Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial.", "journal": "J Clin Oncol", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22184384/", "doi": "10.1200/JCO.2011.39.1953", "errata": [] }, { "key": "P-ARTISTFINAL", "pmid": "25559811", "title": "Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset Analyses.", "journal": "J Clin Oncol", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25559811/", "doi": "10.1200/JCO.2014.58.3930", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Failure to demonstrate superiority is not proof that the treatments are equivalent. The treatment schedules also differed in chemotherapy exposure, so this was not an isolated test of radiotherapy added to an otherwise identical chemotherapy course. Favorable node-positive and histologic subgroup findings do not overturn the overall negative primary comparison. The final publication follows the original trial rather than providing independent replication. Subsequent ARTIST 2 is a separate trial and is assessed separately in the library. The saved abstracts do not provide a quantitative comparison of serious toxicity.", "label": "ARTIST · adjuvant chemotherapy with or without radiotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Adjuvant capecitabine and cisplatin versus chemotherapy combined with radiotherapy after D2 gastrectomy", "population": "Patients with completely resected gastric cancer in the original ARTIST trial", "claim": "The original trial randomized 458 patients. Adding radiotherapy did not significantly improve the primary DFS endpoint (P=.0862). At 7 years of follow-up, DFS remained statistically similar (HR 0.740, 95% CI 0.520–1.050; P=.0922), as did overall survival (HR 1.130, 95% CI 0.775–1.647; P=.5272).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "G-ARTIST", "nct": "NCT00323830", "acronym": null, "title": "Phase III Randomized Trial of Adjuvant XP Chemotherapy and XP/RT for Resected Gastric Adenocarcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 458, "sponsor": "Samsung Medical Center", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2004-10", "lastUpdate": "2011-11-09", "url": "https://clinicaltrials.gov/study/NCT00323830" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (DFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 458, "assessment": "not stated", "quote": "Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy … Of 458 patients, 228 were randomly assigned to the XP arm and 230 to the XP/XRT/XP arm." }, "effect": { "measure": "HR", "value": 0.74, "ci_low": 0.52, "ci_high": 1.05, "ci_level": "95%", "p": "P=.0922", "endpoint": "Disease-free survival at 7 years of follow-up (final report)", "quote": "With 7 years of follow-up, DFS remained similar between treatment arms (hazard ratio [HR], 0.740; 95% CI, 0.520 to 1.050; P=.0922)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In 458 patients with D2-resected gastric cancer, ARTIST compared 6 cycles of adjuvant capecitabine plus cisplatin (XP) with XP plus capecitabine chemoradiotherapy (XP/XRT/XP), and after 7 years of follow-up disease-free survival was not significantly different (HR 0.740, 95% CI 0.520 to 1.050; P=.0922); overall survival was also similar (HR 1.130, 95% CI 0.775 to 1.647; P=.5272). The abstracts do not report grade 3 or higher toxicity rates; treatment was completed as planned by 81.7% in the chemoradiotherapy arm and 75.4% in the chemotherapy-alone arm.", "takeaway_ko": "D2 위절제술을 받은 위암 환자 458명을 대상으로 ARTIST 연구는 보조 capecitabine·cisplatin(XP) 6주기와 XP에 capecitabine 병용 동시항암방사선치료를 추가한 요법(XP/XRT/XP)을 비교했으며, 7년 추적 결과 무병생존은 유의한 차이가 없었고(HR 0.740, 95% CI 0.520–1.050; P=.0922) 전체생존도 유사했습니다(HR 1.130, 95% CI 0.775–1.647; P=.5272). 초록에는 3등급 이상 이상반응 발생률이 보고되지 않았고, 계획된 치료 완료율은 항암방사선치료군 81.7%, 항암화학요법 단독군 75.4%였습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CM8HW", "trial": "C-CM8HW", "papers": [ { "key": "P-CM8HW", "pmid": "39602630", "title": "Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.", "journal": "N Engl J Med", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39602630/", "doi": "10.1056/NEJMoa2402141", "errata": [] }, { "key": "P-CM8HWNIVO", "pmid": "39874977", "title": "Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.", "journal": "Lancet", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39874977/", "doi": "10.1016/S0140-6736(24)02848-4", "errata": [ { "pmid": "40023649", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/40023649/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "These are distinct prespecified interim PFS analyses within one trial, with overlapping participants; the reports are not independent replications and their denominators must not be added. The all-lines comparison is not a first-line-only estimate. PFS superiority does not establish overall-survival benefit, cure, or safety equivalence. Metastatic biomarker-selected results cannot be transferred to all colorectal cancers or to organ preservation in localized rectal cancer. The publisher correction identifies an appendix amendment without itemizing its changes. This unit uses saved PubMed abstracts, checked against the current publisher abstract, and makes no appendix-derived claim.", "label": "CheckMate 8HW · dual immunotherapy in MSI-H/dMMR metastatic colorectal cancer", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Nivolumab plus ipilimumab versus chemotherapy in the first line, and versus nivolumab across treatment lines", "population": "Immunotherapy-naive patients with unresectable or metastatic MSI-H/dMMR colorectal cancer; primary efficacy analyses used central confirmation", "claim": "The first-line chemotherapy comparison randomized 303 patients, of whom 255 had centrally confirmed MSI-H/dMMR disease; 24-month PFS was 72% with the combination versus 14% with chemotherapy. The separate comparison with nivolumab, across all treatment lines, randomized 354 versus 353 patients; 296 and 286 of them, respectively, had centrally confirmed MSI-H/dMMR disease. PFS favored the combination over nivolumab (HR 0.62, 95% CI 0.48–0.81; P=0.0003). In the treated safety populations, grade 3 or 4 treatment-related adverse events occurred in 78 of 352 patients (22%) versus 50 of 351 (14%); three treatment-related deaths occurred across these two arms.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "C-CM8HW", "nct": "NCT04008030", "acronym": "CheckMate 8HW", "title": "A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 839, "sponsor": "Bristol-Myers Squibb", "sponsorClass": "INDUSTRY", "collaborators": [ "Ono Pharmaceutical Co., Ltd." ], "hasResults": true, "start": "2019-08-05", "lastUpdate": "2026-08-20", "url": "https://clinicaltrials.gov/study/NCT04008030" }, "sources": 3, "corrections": 1, "analysisRecord": null }, { "id": "U-APT", "trial": "B-APT", "papers": [ { "key": "P-APT", "pmid": "25564897", "title": "Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25564897/", "doi": "10.1056/NEJMoa1406281", "errata": [ { "pmid": "26559595", "title": "Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/26559595/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-APT10y", "pmid": "36858723", "title": "Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial.", "journal": "Lancet Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36858723/", "doi": "10.1016/S1470-2045(23)00051-7", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "This uncontrolled trial does not establish comparative benefit, equivalence to more intensive regimens, or cure. The protocol permitted limited nodal micrometastatic disease after amendment, so the trial label must not imply strictly node-negative enrollment throughout. Invasive disease-free survival includes contralateral cancers and deaths and is not recurrence alone. The published correction changed the body-text neuropathy count; the corrected count agrees with the saved abstract. Long-term follow-up and the original report concern the same cohort.", "label": "APT · long-term outcomes after limited adjuvant chemotherapy", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "Postoperative paclitaxel plus trastuzumab followed by trastuzumab alone", "population": "Patients with small HER2-positive early breast cancer meeting the APT nodal eligibility criteria", "claim": "Of 410 enrolled patients, 406 started protocol therapy. At a median follow-up of 10·8 years, 10-year invasive disease-free survival was 91·3% (95% CI 88·3–94·4), the recurrence-free interval 96·3% (95% CI 94·3–98·3), and overall survival 94·3% (95% CI 91·8–96·8). The original report recorded grade 3 neuropathy in 13 patients (3.2%) and symptomatic congestive heart failure in 2 (0.5%).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-APT", "nct": "NCT00542451", "acronym": null, "title": "Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 406, "sponsor": "Dana-Farber Cancer Institute", "sponsorClass": "OTHER", "collaborators": [ "Brigham and Women's Hospital", "Beth Israel Deaconess Medical Center", "Massachusetts General Hospital", "Genentech, Inc." ], "hasResults": true, "start": "2007-10", "lastUpdate": "2024-06-26", "url": "https://clinicaltrials.gov/study/NCT00542451" }, "sources": 3, "corrections": 1, "analysisRecord": null }, { "id": "U-PERSEPHONE", "trial": "B-PERSEPHONE", "papers": [ { "key": "P-PERSEPHONE", "pmid": "31178152", "title": "6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial.", "journal": "Lancet", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31178152/", "doi": "10.1016/S0140-6736(19)30650-6", "errata": [] }, { "key": "P-PERSEPHONE2020", "pmid": "32880572", "title": "Six versus 12 months' adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT.", "journal": "Health Technol Assess", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32880572/", "doi": "10.3310/hta24400", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Non-inferiority within the specified margin does not mean identical efficacy or establish universal interchangeability. The updated report and earlier publication describe the same trial and have different follow-up and safety analysis denominators. Chemotherapy regimens and trastuzumab scheduling changed during recruitment. This comparison does not establish the effect of a much shorter course, dual HER2 blockade, or a post-neoadjuvant residual-disease regimen.", "label": "PERSEPHONE · shorter adjuvant trastuzumab duration", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Six versus twelve months of adjuvant trastuzumab with chemotherapy", "population": "Patients with HER2-positive early breast cancer for whom chemotherapy and trastuzumab were planned", "claim": "The updated report included 4088 patients at median 6.1 years of follow-up. Four-year DFS was 89.5% with six months versus 90.3% with twelve months (HR 1.10, 90% CI 0.96–1.26; non-inferiority P=.01), meeting the prespecified non-inferiority criterion based on a 3% absolute DFS margin. Early discontinuation for cardiotoxicity occurred in 61/1977 (3%) versus 146/1941 (8%), respectively (P<.0001).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-PERSEPHONE", "nct": "NCT00712140", "acronym": null, "title": "Trastuzumab in Treating Women With HER2-Positive Early Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 4000, "sponsor": "Warwick Medical School", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2007-10", "lastUpdate": "2011-09-02", "url": "https://clinicaltrials.gov/study/NCT00712140" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (4-year disease-free survival, non-inferiority margin of 3%)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 4088, "assessment": "not stated", "quote": "This study is an open-label, randomised phase 3 non-inferiority trial. … A total of 4088 patients with HER2-positive early breast cancer who it was planned would receive both chemotherapy and trastuzumab took part.", "quote_note": "P-PERSEPHONE 2019" }, "effect": { "measure": "HR", "value": 1.1, "ci_low": 0.96, "ci_high": 1.26, "ci_level": "90%", "p": "non-inferiority p = 0.01", "endpoint": "Disease-free survival (6 months vs 12 months trastuzumab)", "quote": "hazard ratio 1.10, 90% confidence interval 0.96 to 1.26; non-inferiority p = 0.01", "quote_note": "P-PERSEPHONE2020, 6.1 years' median follow-up" }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "4 years", "experimental_pct": 89.5, "control_pct": 90.3, "higher_is_better": true, "experimental_arm": "6 months trastuzumab", "control_arm": "12 months trastuzumab", "quote": "At 6.1 years' median follow-up, with 389 (10%) deaths and 566 (14%) disease-free survival events, the 4-year disease-free survival rates for the 4088 patients were 89.5% (95% confidence interval 88.1% to 90.8%) in the 6-month group and 90.3% (95% confidence interval 88.9% to 91.5%) in the 12-month group", "difference_pp": -0.8, "nnt": null, "nnt_label": "favours control", "quote_note": "P-PERSEPHONE2020, more recent update; earlier 2019 report at 5·4 years: 89·4% vs 89·8%", "nnh": 125 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 3, "discontinuation_control_pct": 8, "treatment_related_deaths": null, "quote": "Six months' trastuzumab resulted in fewer patients reporting adverse events of severe grade [365/1929 (19%) vs. 460/1935 (24%) for 12-month patients; p = 0.0003] or stopping early because of cardiotoxicity [61/1977 (3%) vs. 146/1941 (8%) for 12-month patients; p < 0.0001].", "quote_note": "P-PERSEPHONE2020; discontinuation is for cardiotoxicity only; 'severe grade' AEs are not explicitly defined as grade ≥3, so grade3plus fields are left null" }, "takeaway_en": "In 4088 patients with HER2-positive early breast cancer receiving chemotherapy, 6 months of adjuvant trastuzumab was compared with the standard 12 months and met the non-inferiority criterion. Four-year disease-free survival was 89.5% versus 90.3% (HR 1.10, 90% CI 0.96–1.26). In exchange, the shorter course had fewer severe adverse events (19% vs 24%) and fewer early stops for cardiotoxicity (3% vs 8%).", "takeaway_ko": "항암화학요법을 받는 HER2 양성 조기 유방암 환자 4088명에서 보조 트라스투주맙 6개월 투여를 표준 12개월 투여와 비교하였고, 6개월 투여는 비열등성 기준을 충족하였습니다. 4년 무병생존율은 89.5% 대 90.3%였습니다(HR 1.10, 90% CI 0.96–1.26). 반면 6개월 투여군에서 중증 이상반응(19% 대 24%)과 심장독성으로 인한 조기 중단(3% 대 8%)이 더 적었습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TRAIN2", "trial": "B-TRAIN2", "papers": [ { "key": "P-TRAIN2", "pmid": "30413379", "title": "Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30413379/", "doi": "10.1016/S1470-2045(18)30570-9", "errata": [] }, { "key": "P-TRAIN2-3y", "pmid": "34014249", "title": "Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial.", "journal": "JAMA Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34014249/", "doi": "10.1001/jamaoncol.2021.1371", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The primary comparison did not demonstrate increased pathological complete response from adding anthracyclines; this does not mean either regimen lacked activity. Response evaluability, randomized survival analyses, and treatment-received safety populations have different denominators. Survival was a secondary follow-up analysis, and nonsignificant comparisons do not prove equivalence or non-inferiority. Pathological complete response is not cure. Both arms included dual HER2 blockade, so the finding cannot isolate the effect of either antibody alone.", "label": "TRAIN-2 · anthracycline contribution with dual HER2 blockade", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Neoadjuvant anthracycline-containing versus anthracycline-free chemotherapy, both with trastuzumab and pertuzumab", "population": "Patients with previously untreated stage II–III HER2-positive breast cancer", "claim": "Among 438 randomized patients, in the population evaluable for the primary endpoint, pathological complete response occurred in 141/212 (67%) with anthracyclines versus 140/206 (68%) without them (P=0·95). In follow-up of the randomized population, 3-year EFS was 92.7% versus 93.6%; the EFS HR favoring the nonanthracycline arm was 0.90 (95% CI 0.50–1.63). Grade 3 or worse febrile neutropenia occurred in 23/220 versus 3/218 in the treatment-received safety populations.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-TRAIN2", "nct": "NCT01996267", "acronym": "TRAIN-2", "title": "Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 437, "sponsor": "The Netherlands Cancer Institute", "sponsorClass": "OTHER", "collaborators": [ "Roche Pharma AG", "Borstkanker Onderzoek Groep" ], "hasResults": false, "start": "2013-12", "lastUpdate": "2024-03-29", "url": "https://clinicaltrials.gov/study/NCT01996267" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Proportion of patients who achieved a pathological complete response in breast and axilla (ypT0/is ypN0) in the intention-to-treat population", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 438, "assessment": "not stated", "quote": "The TRAIN-2 study is an open-label, randomised, controlled, phase 3 trial being done in 37 hospitals in the Netherlands. … Between Dec 9, 2013, and Jan 14, 2016, 438 patients were enrolled and randomly assigned to the two treatment groups (219 patients to each group)" }, "effect": { "measure": "HR", "value": 0.9, "ci_low": 0.5, "ci_high": 1.63, "ci_level": "95%", "p": null, "endpoint": "Event-free survival (secondary analysis, 3-year follow-up; HR favoring nonanthracycline arm). The primary endpoint (pCR) has no HR; its p=0·95.", "quote": "A total of 23 EFS events (10.5%) occurred in the anthracycline group and 21 EFS events (9.6%) occurred in the nonanthracycline group (hazard ratio, 0.90; 95% CI, 0.50-1.63; favoring nonanthracyclines)." }, "landmark": [ { "endpoint": "Pathological complete response (ypT0/is ypN0)", "timepoint": "After neoadjuvant therapy (surgery)", "experimental_pct": 67, "control_pct": 68, "higher_is_better": true, "experimental_arm": "FEC ×3 then paclitaxel-carboplatin ×6 + trastuzumab-pertuzumab (anthracycline)", "control_arm": "Paclitaxel-carboplatin ×9 + trastuzumab-pertuzumab (nonanthracycline)", "quote": "A pathological complete response was recorded in 141 (67%, 95% CI 60-73) of 212 patients in the anthracycline group and in 140 (68%, 61-74) of 206 in the non-anthracycline group (p=0·95).", "difference_pp": -1, "nnt": null, "nnt_label": "favours control", "quote_note": "Primary analysis (Lancet Oncol 2018", "nnh": 100 }, { "endpoint": "Event-free survival", "timepoint": "3 years", "experimental_pct": 92.7, "control_pct": 93.6, "higher_is_better": true, "experimental_arm": "Anthracycline-containing regimen + trastuzumab-pertuzumab", "control_arm": "Nonanthracycline regimen + trastuzumab-pertuzumab", "quote": "Three-year EFS estimates were 92.7% (95% CI, 89.3%-96.2%) in the anthracycline group and 93.6% (95% CI, 90.4%-96.9%) in the nonanthracycline group", "difference_pp": -0.9, "nnt": null, "nnt_label": "favours control", "quote_note": "3-year follow-up (JAMA Oncol 2021, median follow-up 48.8 months", "nnh": 112 }, { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 97.7, "control_pct": 98.2, "higher_is_better": true, "experimental_arm": "Anthracycline-containing regimen + trastuzumab-pertuzumab", "control_arm": "Nonanthracycline regimen + trastuzumab-pertuzumab", "quote": "3-year OS estimates were 97.7% (95% CI, 95.7%-99.7%) in the anthracycline group and 98.2% (95% CI, 96.4%-100%) in the nonanthracycline group.", "difference_pp": -0.5, "nnt": null, "nnt_label": "favours control", "quote_note": "3-year follow-up (JAMA Oncol 2021", "nnh": 200 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "One patient in the anthracycline group died because of a pulmonary embolism, which was possibly treatment related.", "quote": "Grade 3 or worse febrile neutropenia was more common in the anthracycline group than in the non-anthracycline group (23 [10%] vs three [1%], p<0·0001). … One patient in the anthracycline group died because of a pulmonary embolism, which was possibly treatment related. … A decline in left ventricular ejection fraction of 10% or more from baseline to less than 50% was more common in patients who received anthracyclines than those who did not (17 of 220 [7.7%] vs 7 of 218 [3.2%]; P = .04). Two patients treated with anthracyclines developed acute leukemia." }, "takeaway_en": "In 438 patients with previously untreated stage II–III HER2-positive breast cancer receiving neoadjuvant trastuzumab plus pertuzumab, adding anthracyclines (FEC followed by paclitaxel-carboplatin) to an anthracycline-free paclitaxel-carboplatin regimen gave similar pathological complete response rates (67% vs 68%). At 3-year follow-up, event-free survival was also similar (92.7% vs 93.6%; HR 0.90, 95% CI 0.50–1.63, favoring the anthracycline-free arm), but the anthracycline arm had more grade 3 or worse febrile neutropenia (10% vs 1%) and more LVEF decline (7.7% vs 3.2%), and 2 patients in that arm developed acute leukemia.", "takeaway_ko": "이전 치료력이 없는 2–3기 HER2 양성 유방암 환자 438명에게 트라스투주맙과 퍼투주맙을 병용한 선행요법을 시행했습니다. 무안트라사이클린 파클리탁셀-카보플라틴 요법과 안트라사이클린 포함 요법(FEC 후 파클리탁셀-카보플라틴)을 비교한 결과, 병리학적 완전관해율은 67% 대 68%로 비슷했습니다. 3년 추적에서 무사건생존율도 92.7% 대 93.6%로 비슷했으나(위험비 0.90, 95% 신뢰구간 0.50–1.63, 무안트라사이클린군에 유리), 안트라사이클린군에서 3등급 이상 발열성 호중구감소증(10% 대 1%)과 좌심실 박출률 감소(7.7% 대 3.2%)가 더 많았고 급성 백혈병이 2명에서 발생했습니다.", "certainty": { "level": "very low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "confidence interval includes no effect", "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ShortHER", "trial": "B-ShortHER", "papers": [ { "key": "P-ShortHER", "pmid": "30219886", "title": "Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.", "journal": "Ann Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30219886/", "doi": "10.1093/annonc/mdy414", "errata": [] }, { "key": "P-ShortHER10y", "pmid": "37748109", "title": "Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37748109/", "doi": "10.1200/JCO.23.00790", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Similar long-term point estimates and exploratory nodal subgroups do not reverse the failed non-inferiority conclusion or demonstrate equivalence. Recruitment below the original target limited statistical power. Chemotherapy schedules and doses also differed between arms, so the comparison does not isolate trastuzumab duration. The original abstract's stated total and listed arm counts do not sum consistently; no arm-specific denominator is inferred here. The primary and final reports describe one trial, not independent replication.", "label": "ShortHER · non-inferiority was not established for a brief trastuzumab strategy", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Nine weeks versus one year of adjuvant trastuzumab with different anthracycline-taxane chemotherapy schedules", "population": "Patients with resected HER2-positive breast cancer who were node-positive or node-negative with at least one specified risk factor", "claim": "The original report stated that 1254 patients were randomized. The primary DFS analysis did not establish non-inferiority: the short-versus-long treatment HR was 1.13 (90% CI 0.89–1.42), crossing the prespecified 1.29 margin. The final report, which included the second coprimary endpoint, OS, had a median follow-up of 9 years; 10-year DFS was 77% with one year versus 78% with nine weeks, and OS was 89% versus 88%, respectively.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ShortHER", "nct": "NCT00629278", "acronym": null, "title": "Combination Chemotherapy and Trastuzumab in Treating Women With Stage I, Stage II, or Stage III HER2-Positive Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 2500, "sponsor": "Azienda Ospedaliero-Universitaria di Modena", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2007-12", "lastUpdate": "2013-08-07", "url": "https://clinicaltrials.gov/study/NCT00629278" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (DFS); overall survival (OS) was the second coprimary end point in the final analysis", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 1254, "assessment": "not stated", "quote": "A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626)." }, "effect": { "measure": "HR", "value": 1.13, "ci_low": 0.89, "ci_high": 1.42, "ci_level": "90%", "p": null, "endpoint": "DFS, short (9 weeks) vs long (1 year) trastuzumab; non-inferiority margin HR <1.29", "quote": "The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin." }, "landmark": [ { "endpoint": "DFS", "timepoint": "10 years", "experimental_pct": 78, "control_pct": 77, "higher_is_better": true, "experimental_arm": "9-week trastuzumab plus anthracycline-taxane chemotherapy (arm B, short)", "control_arm": "1-year trastuzumab plus anthracycline-taxane chemotherapy (arm A, long)", "quote": "At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively.", "difference_pp": 1, "nnt": 100, "quote_note": "From the 2023 10-year update (supersedes 5-year DFS of 88% long vs 85% short in the 2018 report" }, { "endpoint": "OS", "timepoint": "10 years", "experimental_pct": 88, "control_pct": 89, "higher_is_better": true, "experimental_arm": "9-week trastuzumab plus anthracycline-taxane chemotherapy (arm B, short)", "control_arm": "1-year trastuzumab plus anthracycline-taxane chemotherapy (arm A, long)", "quote": "Ten-year OS is 89% versus 88% in the long versus short arm, respectively.", "difference_pp": -1, "nnt": null, "nnt_label": "favours control", "quote_note": "From the 2023 10-year update (supersedes 5-year OS of 95.2% long vs 95.0% short in the 2018 report", "nnh": 100 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001)." }, "takeaway_en": "In patients with resected HER2-positive early breast cancer receiving anthracycline-taxane chemotherapy, 9 weeks of trastuzumab failed to show non-inferiority to 1 year for DFS (HR 1.13, 90% CI 0.89-1.42), although at 10 years DFS was 78% versus 77% and OS was 88% versus 89%. The shorter course had fewer cardiac events (risk ratio 0.33), but in patients with N4+ disease the 10-year OS was 64% with 9 weeks versus 84% with 1 year.", "takeaway_ko": "항암화학요법(anthracycline-taxane)을 받는 절제된 HER2 양성 조기 유방암 환자에서 trastuzumab 9주 투여는 1년 투여 대비 무병생존(DFS)의 비열등성을 입증하지 못했으나(HR 1.13, 90% CI 0.89-1.42), 10년 무병생존율은 78% 대 77%, 10년 전체생존율은 88% 대 89%였습니다. 단기 투여군에서 심장 사건이 더 적었으나(위험비 0.33), 림프절 4개 이상 전이(N4+) 환자에서는 10년 전체생존율이 9주군 64%, 1년군 84%였습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ATTRACTION2", "trial": "G-ATTRACTION2", "papers": [ { "key": "P-ATTRACTION2", "pmid": "28993052", "title": "Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28993052/", "doi": "10.1016/S0140-6736(17)31827-5", "errata": [] }, { "key": "P-ATTRACTION2-3y", "pmid": "33743112", "title": "Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab.", "journal": "Gastric Cancer", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33743112/", "doi": "10.1007/s10120-021-01173-w", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The safety population differs from the randomized denominator in the placebo arm. The long-term report follows the same trial and is not independent replication. Treatment beyond progression and responder survival were selected subgroup analyses; they do not establish a causal benefit from continuing nivolumab after progression. This later-line, checkpoint-inhibitor-naive East Asian population and placebo comparison do not establish benefit after prior checkpoint blockade or rank current active treatment options.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "ATTRACTION-2 · later-line nivolumab with long-term follow-up", "result": "positive", "setting": "Nivolumab versus placebo after at least two previous chemotherapy regimens", "population": "Checkpoint-inhibitor-naive patients with unresectable advanced or recurrent gastric or gastroesophageal junction cancer in Japan, South Korea and Taiwan", "claim": "The trial randomized 493 patients to nivolumab (330) or placebo (163). At the 3-year update, median OS was 5.3 versus 4.1 months (HR 0.62, 95% CI 0.50–0.75; P<.0001), with 3-year survival of 5.6% versus 1.9%. The original report recorded grade 3 or 4 treatment-related adverse events in 34/330 nivolumab-treated patients and 7/161 placebo-treated patients; treatment-related deaths occurred in 5/330 and 2/161.", "trialRecord": { "key": "G-ATTRACTION2", "nct": "NCT02267343", "acronym": null, "title": "Study of ONO-4538 in Unresectable Advanced or Recurrent Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 493, "sponsor": "Ono Pharmaceutical Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2014-10", "lastUpdate": "2024-05-03", "url": "https://clinicaltrials.gov/study/NCT02267343" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival in the intention-to-treat population", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 493, "assessment": "not stated", "quote": "In this randomised, double-blind, placebo-controlled, phase 3 trial done at 49 clinical sites in Japan, South Korea, and Taiwan … we randomly assigned 493 patients to receive nivolumab (n=330) or placebo (n=163)." }, "effect": { "measure": "HR", "value": 0.62, "ci_low": 0.5, "ci_high": 0.75, "ci_level": "95%", "p": "P < 0.0001", "endpoint": "Overall survival (3-year update)", "quote": "With a median follow-up of 38.5 (range 36.1-47.5) months, OS of the nivolumab group was significantly longer compared to the placebo group (median 5.3 vs 4.1 months; 3-year survival rate, 5.6% vs 1.9%; hazard ratio [HR], 0.62 [95% confidence interval (CI) 0.50-0.75], P < 0.0001).", "quote_note": "3-year update (Gastric Cancer 2021" }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 5.6, "control_pct": 1.9, "higher_is_better": true, "experimental_arm": "Nivolumab", "control_arm": "Placebo", "quote": "3-year survival rate, 5.6% vs 1.9%", "difference_pp": 3.7, "nnt": 28, "quote_note": "3-year update (Gastric Cancer 2021, median follow-up 38.5 months" }, { "endpoint": "Overall survival", "timepoint": "12 months", "experimental_pct": 26.2, "control_pct": 10.9, "higher_is_better": true, "experimental_arm": "Nivolumab", "control_arm": "Placebo", "quote": "12-month overall survival rates were 26·2% (95% CI 20·7-32·0) with nivolumab and 10·9% (6·2-17·0) with placebo.", "difference_pp": 15.3, "nnt": 7, "quote_note": "Original report (Lancet 2017, data cutoff Aug 13, 2016); not reported in the 3-year update" } ], "harms": { "grade3plus_experimental_pct": 10, "grade3plus_control_pct": 4, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "5/330 (2%) with nivolumab vs 2/161 (1%) with placebo", "quote": "Grade 3 or 4 treatment-related adverse events occurred in 34 (10%) of 330 patients who received nivolumab and seven (4%) of 161 patients who received placebo; treatment-related adverse events led to death in five (2%) of 330 patients in the nivolumab group and two (1%) of 161 patients in the placebo group.", "quote_note": "Original report (Lancet 2017" }, "takeaway_en": "In checkpoint-inhibitor-naive Asian patients with advanced gastric or gastro-oesophageal junction cancer after at least two prior chemotherapy regimens, nivolumab was compared with placebo; at the 3-year update, 3-year survival was 5.6% versus 1.9%, and in the original report 12-month survival was 26.2% versus 10.9% (HR 0.62 at 3 years). Grade 3 or 4 treatment-related adverse events occurred in 10% versus 4% of patients, and treatment-related deaths in 2% versus 1%.", "takeaway_ko": "두 가지 이상의 이전 항암화학요법을 받은 면역관문억제제 치료 경험이 없는 아시아인 진행성 위암 또는 위식도접합부암 환자를 대상으로 니볼루맙과 위약을 비교했습니다. 3년 업데이트에서 3년 생존율은 5.6% 대 1.9%였고, 최초 보고에서 12개월 생존율은 26.2% 대 10.9%였습니다(3년 시점 위험비 0.62). 3등급 또는 4등급 치료 관련 이상반응은 10% 대 4%에서 발생했으며, 치료 관련 사망은 2% 대 1%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-INTEGRATE2A", "trial": "G-INTEGRATE2A", "papers": [ { "key": "P-INTEGRATE2A", "pmid": "39365958", "title": "INTEGRATE IIa Phase III Study: Regorafenib for Refractory Advanced Gastric Cancer.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39365958/", "doi": "10.1200/JCO.24.00055", "errata": [] }, { "key": "P-INTEGRATE2A-QOL", "pmid": "41071419", "title": "Health-related quality-of-life outcomes with regorafenib in advanced gastric and esophagogastric junction cancer: results from the INTEGRATE trials.", "journal": "Gastric Cancer", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41071419/", "doi": "10.1007/s10120-025-01670-2", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary testing procedure first tested pooled INTEGRATE I and IIa survival, then IIa alone; the phase III result cited here must not be confused with the pooled estimate. The quality-of-life report reuses the trial population and is not independent replication, and its composite endpoint is not a direct measure of symptom improvement alone. The latest submitted registry entry has a slightly different enrollment count from the publication; the efficacy and quality-of-life denominators here follow the published abstracts. The placebo comparison and absence of significant adjusted subgroup differences do not establish superiority over active later-line options or equivalent effects across subgroups.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "INTEGRATE IIa · refractory gastric cancer survival and quality of life", "result": "positive", "setting": "Regorafenib plus best supportive care versus placebo plus best supportive care after at least two previous therapies", "population": "Patients with advanced or metastatic gastric or esophagogastric junction cancer from Asia and the rest of the world", "claim": "The phase III publication reports 251 participants. In INTEGRATE IIa alone, OS favored regorafenib (HR 0.68, 95% CI 0.52–0.90; P=.006); median OS was 4.5 versus 4.0 months. The subsequent quality-of-life report included 240/251 participants and found longer survival free of global-health deterioration (HR 0.68, 95% CI 0.52–0.89; P=.004), a composite endpoint that included deterioration, progression or death. Longitudinal quality-of-life trajectories showed no appreciable difference, while several symptoms, side effects and coping difficulties were more frequent with regorafenib.", "trialRecord": { "key": "G-INTEGRATE2A", "nct": "NCT02773524", "acronym": "INTEGRATEIIa", "title": "A Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 250, "sponsor": "Australasian Gastro-Intestinal Trials Group", "sponsorClass": "NETWORK", "collaborators": [ "Canadian Cancer Trials Group", "Academic and Community Cancer Research United", "National Health and Medical Research Council, Australia" ], "hasResults": false, "start": "2016-11", "lastUpdate": "2022-01-13", "url": "https://clinicaltrials.gov/study/NCT02773524" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 251, "assessment": "not stated", "quote": "A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment … INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo." }, "effect": { "measure": "HR", "value": 0.68, "ci_low": 0.52, "ci_high": 0.9, "ci_level": "95%", "p": ".006", "endpoint": "Overall survival (INTEGRATE IIa cohort alone)", "quote": "INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months" }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "12 months", "experimental_pct": 19, "control_pct": 6, "higher_is_better": true, "experimental_arm": "Regorafenib + best supportive care", "control_arm": "Placebo + best supportive care", "quote": "12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively.", "difference_pp": 13, "nnt": 8, "quote_note": "From P-INTEGRATE2A (J Clin Oncol 2025), the only paper that reports this endpoint" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The toxicity profile was consistent with that of previous reports. … Rash, hand-foot syndrome, numbness, and coping difficulties were more frequent with regorafenib." }, "takeaway_en": "In patients with advanced gastric or esophagogastric junction cancer who had received at least two prior therapies, regorafenib plus best supportive care improved 12-month survival compared with placebo plus best supportive care (19% vs 6%; median OS 4.5 vs 4.0 months; HR 0.68). Rash, hand-foot syndrome, numbness and coping difficulties were more frequent with regorafenib, but overall quality-of-life trajectories did not differ appreciably, and grade ≥3 toxicity rates were not reported in the abstracts.", "takeaway_ko": "두 가지 이상의 이전 치료에 실패한 진행성 위암 또는 위식도접합부암 환자에서 레고라페닙과 최선의 지지요법 병용은 위약과 최선의 지지요법 병용에 비해 12개월 생존율을 높였습니다(19% 대 6%; 전체생존기간 중앙값 4.5개월 대 4.0개월; 위험비 0.68). 레고라페닙군에서 발진, 수족증후군, 감각저하(저림) 및 대처의 어려움이 더 흔했지만 전반적인 삶의 질 추이에는 뚜렷한 차이가 없었으며, 3등급 이상 이상반응 비율은 초록에 보고되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PRODIGE23", "trial": "C-PRODIGE23", "papers": [ { "key": "P-PRODIGE23", "pmid": "33862000", "title": "Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33862000/", "doi": "10.1016/S1470-2045(21)00079-6", "errata": [] }, { "key": "P-PRODIGE23-LONG", "pmid": "38986769", "title": "Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial.", "journal": "Ann Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38986769/", "doi": "10.1016/j.annonc.2024.06.019", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Overall survival was a secondary endpoint, and the long-term report follows the same randomized population rather than an independent cohort. Restricted mean survival-time differences are not median-survival differences. The trial compares complete treatment strategies with different preoperative and postoperative chemotherapy exposure; it does not isolate the effect of adding one drug. It does not test omitting surgery or radiotherapy, and its fit, non-metastatic population does not represent every patient with rectal cancer. Toxicity differs across treatment phases, and a favorable disease-control result does not imply absence of serious harm.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "colorectal", "kind": "rct", "level": "clinical", "label": "PRODIGE 23 · intensified neoadjuvant strategy with long-term survival", "result": "positive", "setting": "Neoadjuvant FOLFIRINOX followed by chemoradiotherapy, surgery and shorter adjuvant chemotherapy versus chemoradiotherapy, surgery and longer adjuvant chemotherapy", "population": "Fit adults aged 18–75 years with cT3 or cT4 non-metastatic rectal adenocarcinoma in France", "claim": "The trial randomized 461 patients (231 versus 230). Primary 3-year DFS was 76% versus 69% (stratified HR 0.69, 95% CI 0.49–0.97; P=.034). At a median follow-up of 82.2 months, 7-year OS was 81.9% versus 76.1%, and the difference in restricted mean survival time was 4.37 months (95% CI 0.35–8.38; P=.033). In the original report, serious adverse events over the whole treatment period occurred in 63/231 versus 50/230 participants.", "trialRecord": { "key": "C-PRODIGE23", "nct": "NCT01804790", "acronym": "Néofirinox", "title": "Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 461, "sponsor": "UNICANCER", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2012-01", "lastUpdate": "2025-06-12", "url": "https://clinicaltrials.gov/study/NCT01804790" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-PROSPECT", "trial": "C-PROSPECT", "papers": [ { "key": "P-PROSPECT", "pmid": "37272534", "title": "Preoperative Treatment of Locally Advanced Rectal Cancer.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37272534/", "doi": "10.1056/NEJMoa2303269", "errata": [] }, { "key": "P-PROSPECT-PRO", "pmid": "37270691", "title": "Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048).", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37270691/", "doi": "10.1200/JCO.23.00903", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Selective chemoradiation remained part of the experimental strategy for inadequate tumor shrinkage or FOLFOX intolerance; this was not universal radiation omission. The efficacy report distinguishes randomized patients from those who initiated treatment, and patient-reported outcomes came from a smaller subset. DFS noninferiority does not establish overall-survival superiority, equivalence for every outcome, or absence of treatment burden. These findings apply to the selected population eligible for sphincter-sparing surgery and do not establish radiation omission for T4 tumors or omission of surgery.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "colorectal", "kind": "rct", "level": "clinical", "label": "PROSPECT · FOLFOX with selective chemoradiation before surgery", "result": "positive", "setting": "Preoperative FOLFOX with selective chemoradiation versus routine preoperative fluoropyrimidine chemoradiation", "population": "Patients with node-positive T2 or node-positive/node-negative T3 rectal cancer who were eligible for sphincter-sparing surgery", "claim": "Of 1194 randomized patients, 1128 started treatment (585 FOLFOX, 543 chemoradiotherapy). At median follow-up of 58 months, FOLFOX with selective chemoradiation met the DFS noninferiority criterion (HR 0.92, 90.2% CI 0.74–1.14; margin 1.29; P=.005 for noninferiority). Five-year DFS was 80.8% versus 78.6%. In the FOLFOX group, 53 patients received preoperative and 8 received postoperative chemoradiotherapy. The companion report included patient-reported symptom data from 940 participants; symptom and functional differences varied by treatment phase, while overall health-related quality of life did not differ between groups.", "trialRecord": { "key": "C-PROSPECT", "nct": "NCT01515787", "acronym": null, "title": "PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery", "status": "UNKNOWN", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 1194, "sponsor": "Alliance for Clinical Trials in Oncology", "sponsorClass": "OTHER", "collaborators": [ "National Cancer Institute (NCI)", "Canadian Cancer Trials Group" ], "hasResults": true, "start": "2012-06-12", "lastUpdate": "2024-02-02", "url": "https://clinicaltrials.gov/study/NCT01515787" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-ATEMPT", "trial": "B-ATEMPT", "papers": [ { "key": "P-ATEMPT", "pmid": "34077270", "title": "Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34077270/", "doi": "10.1200/JCO.20.03398", "errata": [] }, { "key": "P-ATEMPT5y", "pmid": "38935923", "title": "Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38935923/", "doi": "10.1200/JCO.23.02170", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The 497-patient analysis population comprises treatment initiators, not all enrolled patients. The invasive DFS objective evaluated T-DM1 against a prespecified benchmark; the trial was not powered to establish comparative invasive DFS superiority or non-inferiority against paclitaxel plus trastuzumab. Similar composite toxicity percentages do not establish safety equivalence, and favorable patient-reported neuropathy or alopecia findings do not override the composite toxicity result. HER2DX analyses used an available-tissue subset and do not establish a treatment-selection rule. The primary and follow-up reports are one trial.", "label": "ATEMPT", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Adjuvant T-DM1 versus paclitaxel plus trastuzumab in stage I disease", "population": "Centrally confirmed HER2-positive stage I breast cancer; randomized phase II trial with separate toxicity-comparison and T-DM1-arm efficacy objectives", "claim": "The primary analysis included 497 patients who initiated protocol therapy (383 T-DM1, 114 paclitaxel plus trastuzumab). Clinically relevant toxicities occurred in 46% vs 47% (P = .83), so the planned reduction in this composite toxicity measure was not demonstrated. In the T-DM1 arm, 3-year invasive DFS was 97.8% (95% CI 96.3-99.3). At a median follow-up of 5.8 years, the same T-DM1 arm had 11 invasive DFS events and a 5-year invasive DFS of 97.0% (95% CI 95.2-98.7).", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-ATEMPT", "nct": "NCT01853748", "acronym": null, "title": "T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 512, "sponsor": "Dana-Farber Cancer Institute", "sponsorClass": "OTHER", "collaborators": [], "hasResults": true, "start": "2013-05", "lastUpdate": "2026-02-19", "url": "https://clinicaltrials.gov/study/NCT01853748" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Co-primary: incidence of clinically relevant toxicities (CRTs) with T-DM1 versus paclitaxel plus trastuzumab (TH), and invasive disease-free survival (iDFS) in patients receiving T-DM1 (single-arm evaluation)", "primary_endpoint_type": "other", "design": { "phase": "2", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). [ … ] The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH)." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": "P = .83", "endpoint": "Incidence of clinically relevant toxicities (T-DM1 vs TH)", "quote": "CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH (P = .83)." }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "5 years", "experimental_pct": 97, "control_pct": 91.1, "higher_is_better": true, "experimental_arm": "T-DM1 for 1 year", "control_arm": "Paclitaxel plus trastuzumab (TH)", "quote": "After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). [ … ] Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%.", "difference_pp": 5.9, "nnt": 17, "quote_note": "From the 2024 5-year report (P-ATEMPT5y" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH (P = .83). [ … ] Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH." }, "takeaway_en": "In patients with centrally confirmed stage I HER2-positive breast cancer, this randomized phase II trial compared 1 year of adjuvant T-DM1 with paclitaxel plus trastuzumab; at a median follow-up of 5.8 years, 5-year invasive disease-free survival was 97.0% with T-DM1 versus 91.1% with paclitaxel plus trastuzumab, although the trial was not powered for this between-arm comparison. T-DM1 did not reduce clinically relevant toxicities (46% vs 47%), but patients reported less neuropathy and alopecia and better work productivity with T-DM1.", "takeaway_ko": "중앙 판정으로 확인된 1기 HER2 양성 유방암 환자를 대상으로 한 이 무작위 배정 2상 임상시험은 1년간의 보조요법 T-DM1과 파클리탁셀·트라스투주맙 병용요법을 비교했습니다. 추적관찰 기간 중앙값 5.8년에서 5년 무침습질환생존율은 T-DM1군 97.0%, 파클리탁셀·트라스투주맙군 91.1%였으나, 이 시험은 두 군 간 비교를 위한 검정력을 갖추지 않았습니다. T-DM1은 임상적으로 의미 있는 독성을 줄이지 못했지만(46% 대 47%), 환자 보고 결과에서는 말초신경병증과 탈모가 적고 업무 생산성이 더 좋았습니다.", "certainty": { "level": "moderate", "reasons": [ "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-HERA", "trial": "B-HERA", "papers": [ { "key": "P-HERA", "pmid": "16236737", "title": "Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.", "journal": "N Engl J Med", "year": "2005", "url": "https://pubmed.ncbi.nlm.nih.gov/16236737/", "doi": "10.1056/NEJMoa052306", "errata": [] }, { "key": "P-HERA11y", "pmid": "28215665", "title": "11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial.", "journal": "Lancet", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28215665/", "doi": "10.1016/S0140-6736(16)32616-2", "errata": [ { "pmid": "30894267", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/30894267/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The two-versus-one-year comparison used a 366-day landmark analysis and should not be treated as the same baseline comparison as trastuzumab versus observation. Of patients assigned to observation, 884 (52%) selectively crossed over to trastuzumab, affecting interpretation of the randomized long-term contrast. The absence of an additional benefit from longer duration is not proof of equivalence. Secondary cardiac endpoints were more frequent with longer exposure; the abstract does not provide their exact safety-analysis denominators. The primary and final reports describe the same trial. The linked correction changes declarations of interest, not the efficacy estimates used here.", "label": "HERA", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Adjuvant trastuzumab for one or two years versus observation after chemotherapy", "population": "Women with HER2-positive early breast cancer after primary surgery, chemotherapy and radiotherapy as indicated; open-label, three-arm phase III trial", "claim": "The final analysis followed 5099 patients in the intention-to-treat population. At a median follow-up of 11 years, one year of trastuzumab, compared with observation, reduced DFS events (HR 0.76, 95% CI 0.68-0.86) and deaths (HR 0.74, 95% CI 0.64-0.86). The separate comparison of two years versus one year did not demonstrate additional DFS benefit (HR 1.02, 95% CI 0.89-1.17). Ten-year DFS estimates were 63% with observation and 69% in each trastuzumab-duration group.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-HERA", "nct": "NCT00045032", "acronym": "HERA", "title": "Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 5099, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "Breast International Group", "European Organisation for Research and Treatment of Cancer - EORTC", "NCIC Clinical Trials Group", "ETOP IBCSG Partners Foundation" ], "hasResults": true, "start": "2001-11", "lastUpdate": "2017-04-27", "url": "https://clinicaltrials.gov/study/NCT00045032" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 5102, "assessment": "not stated", "quote": "HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer … patients were randomly assigned (1:1:1) to receive trastuzumab for 1 year … or for 2 years … or to the observation group. Primary endpoint is disease-free survival, and analyses are in the intention-to-treat population." }, "effect": { "measure": "HR", "value": 0.76, "ci_low": 0.68, "ci_high": 0.86, "ci_level": "95%", "p": null, "endpoint": "Disease-free survival, 1 year of trastuzumab vs observation, median follow-up 11 years", "quote": "After a median follow-up of 11 years (IQR 10·09-11·53), random assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event (HR 0·76, 95% CI 0·68-0·86) and death (0·74, 0·64-0·86) compared with observation." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "10 years", "experimental_pct": 69, "control_pct": 63, "higher_is_better": true, "experimental_arm": "Trastuzumab for 1 year", "control_arm": "Observation", "quote": "Estimates of 10-year disease-free survival were 63% for observation, 69% for 1 year of trastuzumab, and 69% for 2 years of trastuzumab.", "difference_pp": 6, "nnt": 17, "quote_note": "Final analysis, Lancet 2017, median follow-up 11 years." } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Cardiac toxicity remained low in all groups and occurred mostly during the treatment phase. The incidence of secondary cardiac endpoints was 122 (7·3%) in the 2-years trastuzumab group, 74 (4·4%) in the 1-year trastuzumab group, and 15 (0·9%) in the observation group." }, "takeaway_en": "In women with HER2-positive early breast cancer who had completed surgery, chemotherapy and any radiotherapy, 1 year of trastuzumab gave 10-year disease-free survival of 69% versus 63% with observation (HR 0.76; death HR 0.74), even though 52% of the observation group later crossed over to trastuzumab; 2 years gave no further benefit over 1 year (HR 1.02). The main harm was cardiac: secondary cardiac endpoints occurred in 4.4% with 1 year, 7.3% with 2 years, and 0.9% with observation.", "takeaway_ko": "수술, 항암화학요법 및 필요 시 방사선치료를 마친 HER2 양성 조기 유방암 여성에서 트라스투주맙 1년 투여군의 10년 무병생존율은 69%로, 관찰군의 63%보다 높았습니다(위험비 0.76, 사망 위험비 0.74). 이 결과는 관찰군의 52%가 이후 트라스투주맙으로 교차 투여받았음에도 관찰되었으며, 2년 투여는 1년 투여에 비해 추가 이득이 없었습니다(위험비 1.02). 주요 위해는 심장 독성으로, 이차 심장 평가변수 발생률은 1년 투여군 4.4%, 2년 투여군 7.3%, 관찰군 0.9%였습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-EMBRACA", "trial": "B-EMBRACA", "papers": [ { "key": "P-EMBRACA", "pmid": "30110579", "title": "Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.", "journal": "N Engl J Med", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30110579/", "doi": "10.1056/NEJMoa1802905", "errata": [] }, { "key": "P-EMBRACAOS", "pmid": "32828825", "title": "Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.", "journal": "Ann Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32828825/", "doi": "10.1016/j.annonc.2020.08.2098", "errata": [] } ], "pages": [], "targets": [ "PARP1" ], "biomarkers": [ "BM-gBRCA" ], "subtypes": [], "limits": "The demonstrated PFS benefit should not be presented as an established OS benefit; the nonsignificant OS result does not prove absence of any survival effect. Subsequent PARP inhibitor and platinum treatment complicates OS interpretation, and adjustment for subsequent treatment does not replace the randomized primary comparison. The final report distinguishes 412 treated patients (286 talazoparib, 126 chemotherapy) from 431 randomized patients; grade 3-4 adverse events were reported in 69.6% vs 64.3% of the treated groups. Eligibility selected germline BRCA1/2-mutated, HER2-negative disease and does not validate use across all homologous-recombination defects or all breast cancers. The primary PFS and final OS publications are one trial.", "label": "EMBRACA", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Talazoparib versus physician-choice single-agent chemotherapy in advanced disease", "population": "Germline BRCA1/2-mutated, HER2-negative locally advanced or metastatic breast cancer; open-label phase III trial", "claim": "Among 431 randomized patients (287 talazoparib, 144 chemotherapy), blinded independent central review showed median PFS of 8.6 vs 5.6 months (HR 0.54, 95% CI 0.41-0.71; P < .001). In the final OS analysis, median OS was 19.3 vs 19.5 months (HR 0.848, 95% CI 0.670-1.073; P = .17), without a statistically significant OS improvement. Patient-reported global health status, quality of life and breast symptoms favored talazoparib during extended follow-up.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-EMBRACA", "nct": "NCT01945775", "acronym": "EMBRACA", "title": "A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 431, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [ "Medivation, Inc." ], "hasResults": true, "start": "2013-10-14", "lastUpdate": "2022-01-20", "url": "https://clinicaltrials.gov/study/NCT01945775" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by blinded independent central review", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 431, "assessment": "blinded independent central review", "quote": "We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review. … Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy." }, "effect": { "measure": "HR", "value": 0.54, "ci_low": 0.41, "ci_high": 0.71, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001)." }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "Best response (primary analysis)", "experimental_pct": 62.6, "control_pct": 27.2, "higher_is_better": true, "experimental_arm": "Talazoparib", "control_arm": "Physician's choice single-agent chemotherapy", "quote": "The objective response rate was higher in the talazoparib group than in the standard-therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001).", "difference_pp": 35.4, "nnt": 3, "quote_note": "P-EMBRACA, NEJM 2018" }, { "endpoint": "Overall survival", "timepoint": "12 months", "experimental_pct": 71, "control_pct": 74, "higher_is_better": true, "experimental_arm": "Talazoparib", "control_arm": "Physician's choice single-agent chemotherapy", "quote": "Kaplan-Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%)", "difference_pp": -3, "nnt": null, "nnt_label": "favours control", "quote_note": "P-EMBRACAOS final OS analysis, Ann Oncol 2020", "nnh": 34 }, { "endpoint": "Overall survival", "timepoint": "24 months", "experimental_pct": 42, "control_pct": 38, "higher_is_better": true, "experimental_arm": "Talazoparib", "control_arm": "Physician's choice single-agent chemotherapy", "quote": "month 24, 42% (36% to 47%)/38% (30% to 47%)", "difference_pp": 4, "nnt": 25, "quote_note": "P-EMBRACAOS final OS analysis, Ann Oncol 2020" }, { "endpoint": "Overall survival", "timepoint": "36 months", "experimental_pct": 27, "control_pct": 21, "higher_is_better": true, "experimental_arm": "Talazoparib", "control_arm": "Physician's choice single-agent chemotherapy", "quote": "month 36, 27% (22% to 33%)/21% (14% to 29%)", "difference_pp": 6, "nnt": 17, "quote_note": "P-EMBRACAOS final OS analysis, Ann Oncol 2020" } ], "harms": { "grade3plus_experimental_pct": 69.6, "grade3plus_control_pct": 64.3, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. … Hematologic grade 3-4 adverse events (primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively.", "quote_note": "P-EMBRACAOS, Ann Oncol 2020; reported as grade 3-4; P-EMBRACA, NEJM 2018" }, "takeaway_en": "In 431 patients with germline BRCA1/2-mutated, HER2-negative advanced breast cancer, talazoparib was compared with physician's-choice single-agent chemotherapy. Talazoparib improved progression-free survival (median 8.6 vs 5.6 months; HR 0.54) and objective response (62.6% vs 27.2%), but final overall survival did not differ significantly (median 19.3 vs 19.5 months; HR 0.848), and grade 3-4 adverse events occurred in 69.6% vs 64.3%, with hematologic grade 3-4 events (mainly anemia) in 55% vs 38%.", "takeaway_ko": "생식세포 BRCA1/2 변이 HER2 음성 진행성 유방암 환자 431명에서 탈라조파립과 의사 선택 단일 항암화학요법을 비교했습니다. 탈라조파립은 무진행생존기간(중앙값 8.6개월 대 5.6개월, HR 0.54)과 객관적 반응률(62.6% 대 27.2%)을 개선했으나 최종 전체생존기간에는 유의한 차이가 없었고(중앙값 19.3개월 대 19.5개월, HR 0.848), 3-4등급 이상반응은 69.6% 대 64.3%였으며 3-4등급 혈액학적 이상반응(주로 빈혈)은 55% 대 38%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-MOSAIC", "trial": "C-MOSAIC", "papers": [ { "key": "P-MOSAIC", "pmid": "15175436", "title": "Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.", "journal": "N Engl J Med", "year": "2004", "url": "https://pubmed.ncbi.nlm.nih.gov/15175436/", "doi": "10.1056/NEJMoa032709", "errata": [] }, { "key": "P-MOSAIC6y", "pmid": "19451431", "title": "Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial.", "journal": "J Clin Oncol", "year": "2009", "url": "https://pubmed.ncbi.nlm.nih.gov/19451431/", "doi": "10.1200/JCO.2008.20.6771", "errata": [] }, { "key": "P-MOSAIC10y", "pmid": "26527776", "title": "Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study.", "journal": "J Clin Oncol", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26527776/", "doi": "10.1200/JCO.2015.63.4238", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "DFS was the primary endpoint; long-term OS is a follow-up outcome from the same randomized trial. The overall benefit should not be generalized as an established OS benefit for every stage II patient, and different within-stage P values do not by themselves prove a treatment-by-stage interaction. Mismatch-repair and BRAF analyses used an available-specimen subset; their imprecise subgroup estimates do not establish independent predictive biomarkers for oxaliplatin benefit. The oxaliplatin regimen caused sensory neuropathy, so improved efficacy does not imply lower toxicity. These findings concern resected colon cancer and do not directly establish a regimen or duration for rectal cancer. All three publications are counted as one trial.", "label": "MOSAIC", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant oxaliplatin plus fluorouracil and leucovorin versus fluorouracil and leucovorin alone after resection", "population": "Patients with completely resected stage II or III colon cancer; randomized phase III trial", "claim": "Among 2246 randomized patients, three-year DFS was 78.2% with oxaliplatin plus fluorouracil and leucovorin versus 72.9% with fluorouracil and leucovorin alone (HR 0.77; P = .002). At median follow-up of 9.5 years, ten-year OS was 71.7% vs 67.1% overall (HR 0.85; P = .043). For stage III, ten-year OS was 67.1% vs 59.0% (HR 0.80; P = .016); for stage II, it was 78.4% vs 79.5% (HR 1.00; P = .980), with no demonstrated OS improvement in that stage-specific analysis.", "by": "Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "C-MOSAIC", "nct": "NCT00275210", "acronym": null, "title": "MOSAIC - Multicenter International Study of Oxaliplatin/ 5FU-LV in the Adjuvant Treatment of Colon Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 2246, "sponsor": "Sanofi", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "1998-10", "lastUpdate": "2009-04-20", "url": "https://clinicaltrials.gov/study/NCT00275210" }, "sources": 4, "corrections": 0, "analysisRecord": null }, { "id": "U-FIGHT", "trial": "G-FIGHT", "papers": [ { "key": "P-FIGHT", "pmid": "36244398", "title": "Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study.", "journal": "Lancet Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/36244398/", "doi": "10.1016/S1470-2045(22)00603-9", "errata": [] }, { "key": "P-FIGHT-FINAL", "pmid": "38308771", "title": "Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.", "journal": "Gastric Cancer", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38308771/", "doi": "10.1007/s10120-024-01466-w", "errata": [] }, { "key": "P-FIGHT-QOL", "pmid": "41646955", "title": "Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer.", "journal": "ESMO Gastrointest Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/41646955/", "doi": "10.1016/j.esmogo.2024.100095", "errata": [] } ], "pages": [ { "key": "fight-statistical-plan", "title": "FIGHT — published protocol and statistical analysis plans (PDF)", "url": "https://media.springernature.com/original/springer-static/esm/art%3A10.1007%2Fs10120-024-01466-w/MediaObjects/10120_2024_1466_MOESM2_ESM.pdf", "file": "data/sources/pages/fight-statistical-plan.txt" } ], "targets": [ "FGFR2" ], "biomarkers": [], "subtypes": [], "limits": "Both overall final hazard-ratio confidence intervals include no difference. The FGFR2b 2+/3+ in >=10% of tumor cells subgroup analysis is prespecified exploratory per the final article; its stronger estimates do not establish an interchangeable FGFR2-amplification biomarker or a validated treatment-selection rule. The final report and HRQoL analysis reuse this phase 2 trial and are not independent replication. Similar exploratory HRQoL averages do not negate the ocular adverse-event signal or prove equivalent quality of life. These results do not establish superiority over contemporary active first-line regimens or the current status or results of separate phase 3 trials. The primary-report interpretation, the threshold in the published SAP, and the final descriptive analysis must be distinguished; P>.05 alone is not used here to label this exploratory trial a primary-endpoint failure. The SAP document date does not establish that it was fixed before data inspection.", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "program": "gastric", "kind": "rct", "level": "clinical", "label": "FIGHT · FGFR2b-selected bemarituzumab with final follow-up", "result": "mixed", "setting": "First-line bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6", "population": "HER2-non-positive, FGFR2b-selected, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma", "claim": "The randomized phase 2 trial assigned 155 patients to bemarituzumab (77) or placebo (78) with mFOLFOX6. The primary report described the PFS result (HR 0.68, 95% CI 0.44-1.04; P=.073) as not statistically significant and the study as exploratory. The publicly posted primary statistical analysis plan (SAP v1.0, 20 Oct 2020) specifies hierarchical testing at a one-sided 0.1 level, first of PFS and then of OS/ORR. At final follow-up, for which the final article states that no formal hypothesis testing was performed, median PFS was 9.5 versus 7.4 months (HR 0.72, 95% CI 0.49-1.08) and median OS was 19.2 versus 13.5 months (HR 0.77, 95% CI 0.52-1.14). The original safety populations of treated patients numbered 76 and 77; corneal events of any grade occurred in 51 and 8 patients, respectively, and grade 3 corneal events occurred in 18 bemarituzumab-treated patients. Exploratory post hoc HRQoL analyses of the final data found similar trajectories on key scales in both arms.", "trialRecord": { "key": "G-FIGHT", "nct": "NCT03694522", "acronym": "FIGHT", "title": "A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 155, "sponsor": "Five Prime Therapeutics, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Zai Lab (Shanghai) Co., Ltd." ], "hasResults": true, "start": "2018-09-14", "lastUpdate": "2024-02-28", "url": "https://clinicaltrials.gov/study/NCT03694522" }, "sources": 5, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival in the intention-to-treat population", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "double-blind", "n_randomized": 155, "assessment": "investigator", "quote": "In the randomised, double-blind, placebo-controlled phase 2 trial (FIGHT) … 155 were randomly assigned to the bemarituzumab (n=77) or placebo group (n=78). … The primary endpoint was investigator-assessed progression-free survival (PFS)." }, "effect": { "measure": "HR", "value": 0.68, "ci_low": 0.44, "ci_high": 1.04, "ci_level": "95%", "p": "0.073", "endpoint": "Progression-free survival (primary analysis; not statistically significant)", "quote": "median progression-free survival was 9·5 months (95% CI 7·3-12·9) in the bemarituzumab group and 7·4 months (5·8-8·4) in the placebo group (hazard ratio [HR] 0·68 [95% CI 0·44-1·04; p=0·073).", "quote_note": "P-FIGHT, primary analysis; the final analysis reported HR 0.72; 95% CI 0.49-1.08 without formal hypothesis testing" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "3 in the bemarituzumab group (2 sepsis, 1 pneumonia); none in the placebo group", "quote": "All-grade corneal events (adverse events of special interest) occurred in 51 (67%) patients in the bemarituzumab group and eight (10%) in the placebo group; grade 3 corneal events were reported only in 18 (24%) patients in the bemarituzumab group. Treatment-related deaths occurred in three patients in the bemarituzumab group (two due to sepsis, one due to pneumonia) and none in the placebo group." }, "takeaway_en": "In 155 patients with HER2-non-positive, FGFR2b-selected advanced gastric or gastroesophageal junction adenocarcinoma, this exploratory phase 2 trial added bemarituzumab or placebo to first-line mFOLFOX6. At final analysis, median PFS was 9.5 vs 7.4 months (HR 0.72; 95% CI 0.49-1.08) and median OS was 19.2 vs 13.5 months (HR 0.77; 95% CI 0.52-1.14), with no formal significance testing at final analysis and a non-significant primary PFS result; the main harm was corneal events, which occurred in 67% vs 10% of patients, with grade 3 corneal events in 24% of bemarituzumab-treated patients.", "takeaway_ko": "HER2 비양성이면서 FGFR2b 선택된 진행성 위암 또는 위식도접합부 선암 환자 155명을 대상으로 한 탐색적 2상 시험에서, 1차 mFOLFOX6에 베마리투주맙 또는 위약을 추가하여 비교하였습니다. 최종 분석에서 무진행생존기간 중앙값은 9.5개월 대 7.4개월(HR 0.72; 95% CI 0.49-1.08), 전체생존기간 중앙값은 19.2개월 대 13.5개월(HR 0.77; 95% CI 0.52-1.14)이었으나, 1차 무진행생존 분석은 통계적으로 유의하지 않았고 최종 분석에서는 공식적인 가설 검정을 시행하지 않았으며, 주요 위해는 각막 이상반응으로 67% 대 10%에서 발생하였고 베마리투주맙군의 24%에서 3등급 각막 이상반응이 보고되었습니다.", "certainty": { "level": "low", "reasons": [ "confidence interval includes no effect", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RAPIDO", "trial": "C-RAPIDO", "papers": [ { "key": "P-RAPIDO", "pmid": "33301740", "title": "Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33301740/", "doi": "10.1016/S1470-2045(20)30555-6", "errata": [ { "pmid": "33539749", "title": "Correction to Lancet Oncol 2021; 22: 29-42.", "url": "https://pubmed.ncbi.nlm.nih.gov/33539749/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-RAPIDO-5Y", "pmid": "36661037", "title": "Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial.", "journal": "Ann Surg", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36661037/", "doi": "10.1097/SLA.0000000000005799", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The published primary composite includes locoregional failure, distant metastasis, a new colorectal primary or treatment-related death; it is not an overall-survival endpoint. The later locoregional-failure population and the subset with R0/R1 resection have different denominators from the primary eligible population. A nonsignificant overall locoregional-failure comparison must not hide the higher post-resection recurrence rate. This compares complete treatment strategies, including different radiation schedules and chemotherapy timing, rather than isolating one component or establishing safe radiation or surgery omission. The follow-up and subsequent toxicity or wound analyses reuse the trial and are not independent replication. The complete original-article correction fixes the hospital-policy classification of adjuvant chemotherapy recipients in the flow diagram; it does not revise the estimates cited here. The registry describes a different composite death component, second-primary handling and time origin; the estimates here follow the published report rather than assuming registry and publication definitions match.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "colorectal", "kind": "rct", "level": "clinical", "label": "RAPIDO · early treatment failure and later local recurrence", "result": "mixed", "setting": "Short-course radiotherapy followed by chemotherapy and total mesorectal excision versus long-course chemoradiotherapy, surgery and optional adjuvant chemotherapy", "population": "Chemotherapy-fit patients with MRI-defined high-risk, locally advanced rectal adenocarcinoma", "claim": "Of 920 randomized patients, the primary report analyzed 912 eligible patients: 462 in the experimental group and 450 in the standard-care group. The 3-year probability of disease-related treatment failure was 23.7% versus 30.4% (HR 0.75, 95% CI 0.60–0.95; P=.019). The later report, at median follow-up of 5.6 years, found locoregional failure in 54/460 (12%) versus 36/446 (8%; P=.07). After R0/R1 resection, locoregional recurrence occurred in 44/431 (10%) versus 26/428 (6%; P=.027). The later report found that the reductions in disease-related treatment failure and distant metastases persisted despite the higher locoregional recurrence rate.", "trialRecord": { "key": "C-RAPIDO", "nct": "NCT01558921", "acronym": "RAPIDO", "title": "Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 920, "sponsor": "University Medical Center Groningen", "sponsorClass": "OTHER", "collaborators": [ "Karolinska University Hospital", "Leiden University Medical Center", "Uppsala University Hospital", "Dutch Cancer Society" ], "hasResults": true, "start": "2011-06-21", "lastUpdate": "2026-05-01", "url": "https://clinicaltrials.gov/study/NCT01558921" }, "sources": 3, "corrections": 1, "analysisRecord": null }, { "id": "U-RESOLVE", "trial": "G-RESOLVE", "papers": [ { "key": "P-RESOLVE", "pmid": "34252374", "title": "Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34252374/", "doi": "10.1016/S1470-2045(21)00297-7", "errata": [ { "pmid": "34339653", "title": "Correction to Lancet Oncol 2021; 22: 1081-92.", "url": "https://pubmed.ncbi.nlm.nih.gov/34339653/", "reviewed": true, "unresolvedIdentifier": false }, { "pmid": "39914427", "title": "Correction to Lancet Oncol 2021; 22: 1081-92.", "url": "https://pubmed.ncbi.nlm.nih.gov/39914427/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-RESOLVE-FINAL", "pmid": "39952264", "title": "Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): final report of a randomised, open-label, phase 3 trial.", "journal": "Lancet Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39952264/", "doi": "10.1016/S1470-2045(24)00676-4", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "These are modified intention-to-treat analyses of one trial, and the final OS report is not independent replication. The reported comparisons do not establish superiority between the two SOX strategies or against other contemporary perioperative regimens. The complete later correction changes the primary-abstract superiority comparator to adjuvant-CapOx; the saved PubMed primary abstract and the outdated registry outcome description still name adjuvant-SOX. Raw sources are preserved, and prospective specification of the corrected comparison was not independently audited. The earlier correction changes table-legend group labels and appendix material; those artifacts were not independently audited. The final report does not update safety or resection outcomes.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "RESOLVE · corrected comparisons and final survival follow-up", "result": "positive", "setting": "Perioperative SOX or adjuvant SOX versus adjuvant capecitabine/oxaliplatin around D2 gastrectomy", "population": "Treatment-naive cT4a N+ M0 or cT4b Nany M0 gastric or gastroesophageal junction adenocarcinoma suitable for D2 surgery in China", "claim": "The modified intention-to-treat population contained 1022 patients: 345 assigned to adjuvant-CapOx, 340 to adjuvant-SOX and 337 to perioperative-SOX. The initial 3-year DFS rates were 51.1%, 56.5% and 59.4%, respectively. The corrected published comparison favored perioperative-SOX over adjuvant-CapOx (HR 0.77, 95% CI 0.61–0.97); adjuvant-SOX met the reported non-inferiority criterion versus adjuvant-CapOx (HR 0.86, 95% CI 0.68–1.07; margin 1.33). In the final secondary OS analysis, 5-year survival was 52.1%, 61.0% and 60.0%, respectively; the HRs versus adjuvant-CapOx were 0.77 (95% CI 0.61–0.98; P=.033) for adjuvant-SOX and 0.79 (95% CI 0.62–1.00; P=.049) for perioperative-SOX.", "trialRecord": { "key": "G-RESOLVE", "nct": "NCT01534546", "acronym": null, "title": "Phase III Study to Compare Perioperative Chemotherapy of Oxaliplatin Combined With S-1(SOX) Versus SOX or Oxaliplatin With Capecitabine (XELOX) as Post-operative Chemotherapy in Locally Advanced Gastric Adenocarcinoma With D2 Dissection", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 1094, "sponsor": "Peking University", "sponsorClass": "OTHER", "collaborators": [ "Taiho Pharmaceutical Co., Ltd." ], "hasResults": false, "start": "2012-03", "lastUpdate": "2019-09-17", "url": "https://clinicaltrials.gov/study/NCT01534546" }, "sources": 3, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": "3-year disease-free survival (superiority of perioperative-SOX vs adjuvant-CapOx; non-inferiority of adjuvant-SOX vs adjuvant-CapOx, HR margin 1.33), modified intention-to-treat population", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "In this randomised, open-label, phase 3 study … 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population … 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population", "quote_note": "P-RESOLVE; n_randomized left null because the two abstracts describe the 1094 differently, as screened versus randomly assigned" }, "effect": { "measure": "HR", "value": 0.77, "ci_low": 0.61, "ci_high": 0.97, "ci_level": "95%", "p": "Wald p=0·028", "endpoint": "3-year disease-free survival, perioperative-SOX vs adjuvant-CapOx", "quote": "The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group." }, "landmark": [ { "endpoint": "Disease-free survival", "timepoint": "3 years", "experimental_pct": 59.4, "control_pct": 51.1, "higher_is_better": true, "experimental_arm": "Perioperative SOX", "control_arm": "Adjuvant CapOx", "quote": "3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group.", "difference_pp": 8.3, "nnt": 13, "quote_note": "P-RESOLVE (2021; DFS was not updated in the 2025 final report" }, { "endpoint": "Disease-free survival", "timepoint": "3 years", "experimental_pct": 56.5, "control_pct": 51.1, "higher_is_better": true, "experimental_arm": "Adjuvant SOX", "control_arm": "Adjuvant CapOx", "quote": "3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group.", "difference_pp": 5.4, "nnt": 19, "quote_note": "P-RESOLVE (2021; DFS was not updated in the 2025 final report" }, { "endpoint": "Overall survival (secondary endpoint)", "timepoint": "5 years", "experimental_pct": 60, "control_pct": 52.1, "higher_is_better": true, "experimental_arm": "Perioperative SOX", "control_arm": "Adjuvant CapOx", "quote": "The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group.", "difference_pp": 7.9, "nnt": 13, "quote_note": "P-RESOLVE-FINAL (2025, median follow-up 62·8 months" }, { "endpoint": "Overall survival (secondary endpoint)", "timepoint": "5 years", "experimental_pct": 61, "control_pct": 52.1, "higher_is_better": true, "experimental_arm": "Adjuvant SOX", "control_arm": "Adjuvant CapOx", "quote": "The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group.", "difference_pp": 8.9, "nnt": 12, "quote_note": "P-RESOLVE-FINAL (2025, median follow-up 62·8 months" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "No treatment-related deaths were reported.", "quote": "The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported." }, "takeaway_en": "In Chinese patients with cT4a N+ or cT4b gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy, RESOLVE compared perioperative SOX and adjuvant SOX with adjuvant CapOx. Three-year disease-free survival was 59.4% with perioperative SOX and 56.5% with adjuvant SOX versus 51.1% with adjuvant CapOx, and five-year overall survival was 60.0% and 61.0% versus 52.1%. Grade 3–4 neutropenia, the most common severe adverse event, occurred in 10% with perioperative SOX, 8% with adjuvant SOX and 12% with adjuvant CapOx, and no treatment-related deaths were reported.", "takeaway_ko": "RESOLVE 연구는 D2 위절제술을 받는 cT4a N+ 또는 cT4b 위암·위식도접합부 선암 중국인 환자를 대상으로, 수술 전후(주술기) SOX 및 보조 SOX를 보조 CapOx와 비교했습니다. 3년 무병생존율은 주술기 SOX 59.4%, 보조 SOX 56.5%, 보조 CapOx 51.1%였고, 5년 전체생존율은 각각 60.0%, 61.0%, 52.1%였습니다. 가장 흔한 3–4등급 이상반응인 호중구감소증은 주술기 SOX 10%, 보조 SOX 8%, 보조 CapOx 12%에서 발생했으며, 치료 관련 사망은 보고되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TAGS", "trial": "G-TAGS", "papers": [ { "key": "P-TAGS", "pmid": "30355453", "title": "Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30355453/", "doi": "10.1016/S1470-2045(18)30739-3", "errata": [ { "pmid": "30507432", "title": "Correction to Lancet Oncol 2018; 19: 1437-48.", "url": "https://pubmed.ncbi.nlm.nih.gov/30507432/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-TAGS-QOL", "pmid": "32128634", "title": "Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS.", "journal": "Gastric Cancer", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32128634/", "doi": "10.1007/s10120-020-01053-9", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This placebo comparison does not rank active later-line options. The adverse-event percentages use treatment-exposed populations, not the randomized arm totals. QoL analyses had different evaluable durations by arm and a minimum questionnaire-completion threshold; maintained mean scores do not prove equal quality of life or exclude individual burden. The sensitivity analysis that included progression and death changes the deterioration endpoint. Subsequent prior-treatment and weight-loss analyses are exploratory analyses of this same trial, not independent replications or randomized sequencing comparisons. The complete publisher correction concerns plotted points and axis values in the main and appendix figures, plus unspecified minor errors. The cited abstract values match the current publisher abstract; corrected figures and the unspecified minor errors were not independently audited.", "by": "Codex (GPT-6)", "added": "2026-09-30", "program": "gastric", "kind": "rct", "level": "clinical", "label": "TAGS · later-line trifluridine/tipiracil and quality of life", "result": "positive", "setting": "Trifluridine/tipiracil plus best supportive care versus placebo plus best supportive care after at least two chemotherapy regimens", "population": "Previously treated, non-resectable metastatic gastric or gastroesophageal junction adenocarcinoma", "claim": "The trial randomized 507 patients to trifluridine/tipiracil (337) or placebo (170). Median OS was 5.7 versus 3.6 months (HR 0.69, 95% CI 0.56–0.85; two-sided P=.00058). Among treated patients, grade 3 or worse adverse events of any cause were reported in 267 (80%) versus 97 (58%), and each arm had one treatment-related death. Baseline QoL data were available for 496 randomized patients; there was no clinically significant mean deterioration in global health status in either arm over the report's evaluable period.", "trialRecord": { "key": "G-TAGS", "nct": "NCT02500043", "acronym": null, "title": "Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 507, "sponsor": "Taiho Oncology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2016-02-24", "lastUpdate": "2024-09-03", "url": "https://clinicaltrials.gov/study/NCT02500043" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 507, "assessment": "not stated", "quote": "TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries … Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group." }, "effect": { "measure": "HR", "value": 0.69, "ci_low": 0.56, "ci_high": 0.85, "ci_level": "95%", "p": "two-sided p=0·00058", "endpoint": "Overall survival", "quote": "Median overall survival was 5·7 months (95% CI 4·8-6·2) in the trifluridine/tipiracil group and 3·6 months (3·1-4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56-0·85]; one-sided p=0·00029, two-sided p=0·00058)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 80, "grade3plus_control_pct": 58, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "One treatment-related death in each group: cardiopulmonary arrest in the trifluridine/tipiracil group and toxic hepatitis in the placebo group", "quote": "Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group … One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group)." }, "takeaway_en": "In patients with metastatic gastric or gastroesophageal junction adenocarcinoma who had received at least two prior chemotherapy regimens, trifluridine/tipiracil plus best supportive care improved median overall survival compared with placebo plus best supportive care (5.7 vs 3.6 months; HR 0.69, 95% CI 0.56–0.85). Grade 3 or worse adverse events of any cause were more frequent with trifluridine/tipiracil (80% vs 58%), mainly neutropenia (34%) and anaemia (19%), while mean global health status quality of life showed no clinically significant deterioration in either arm during the analysis period.", "takeaway_ko": "두 가지 이상의 이전 항암화학요법을 받은 전이성 위암 또는 위식도접합부 선암 환자에서, 트리플루리딘/티피라실과 최선의 지지요법 병용은 위약과 최선의 지지요법 병용에 비해 전체생존기간 중앙값을 개선했습니다(5.7개월 대 3.6개월; 위험비 0.69, 95% 신뢰구간 0.56–0.85). 원인과 무관한 3등급 이상 이상반응은 트리플루리딘/티피라실군에서 더 많았으며(80% 대 58%), 주로 호중구감소증(34%)과 빈혈(19%)이었습니다. 분석 기간 동안 평균 전반적 건강상태 삶의 질은 두 군 모두에서 임상적으로 유의한 악화를 보이지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-RxPONDER", "trial": "B-RxPONDER", "papers": [ { "key": "P-RxPONDER", "pmid": "34914339", "title": "21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.", "journal": "N Engl J Med", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34914339/", "doi": "10.1056/NEJMoa2108873", "errata": [] }, { "key": "P-RxPONDERAMH", "pmid": "42613139", "title": "Ovarian reserve as a measure of adjuvant chemotherapy benefit in hormone receptor positive (HR-positive), HER2-negative, node-positive breast cancer in SWOG S1007 (RxPONDER).", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42613139/", "doi": "10.1016/j.annonc.2026.05.697", "errata": [ { "pmid": "42901850", "title": "Corrigendum to \"Ovarian reserve as a measure of adjuvant chemotherapy benefit in hormone receptor positive (HR-positive), HER2-negative, node-positive breast cancer in SWOG S1007 (RxPONDER)\": [Annals of Oncology 37 (2026) 1220-1229].", "url": "https://pubmed.ncbi.nlm.nih.gov/42901850/", "reviewed": false, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "These results do not extend to more than three positive nodes or recurrence scores above the enrolled range. A nonsignificant postmenopausal estimate is not proof of zero individual benefit, and invasive DFS is a composite endpoint rather than overall survival. The trial did not randomize chemotherapy against optimized ovarian suppression, so it cannot isolate cytotoxic effects from ovarian effects in younger women. The later ovarian-reserve analysis found treatment-marker interactions in an available-serum subset using predefined cut points and multiplicity adjustment; it was not an independent randomized validation of a biomarker-guided treatment policy. All reports concern the same trial.", "program": "breast", "kind": "rct", "level": "clinical", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "RxPONDER", "result": "mixed", "setting": "Adjuvant endocrine therapy with or without chemotherapy in node-positive disease with a recurrence score of 25 or lower", "population": "Women with hormone receptor-positive, HER2-negative breast cancer, one to three positive axillary nodes and a 21-gene recurrence score of 25 or lower", "claim": "The primary report describes 5083 randomized women and 5018 trial participants. At the prespecified interim analysis, chemotherapy benefit differed by menopausal status (interaction P = .008). Five-year invasive DFS with chemoendocrine versus endocrine-only therapy was 91.3% vs 91.9% in postmenopausal women (HR 1.02, 95% CI 0.82-1.26), without a demonstrated benefit. In premenopausal women it was 93.9% vs 89.0% (HR 0.60, 95% CI 0.43-0.83); distant relapse-free survival also favored chemotherapy (HR 0.58, 95% CI 0.39-0.87). Benefit did not increase with a higher recurrence score within the tested range.", "trialRecord": { "key": "B-RxPONDER", "nct": "NCT01272037", "acronym": null, "title": "Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 5018, "sponsor": "National Cancer Institute (NCI)", "sponsorClass": "NIH", "collaborators": [], "hasResults": true, "start": "2011-02-28", "lastUpdate": "2026-10-26", "url": "https://clinicaltrials.gov/study/NCT01272037" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (effect of chemotherapy and whether it was influenced by the recurrence score)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 5083, "assessment": "not stated", "quote": "The phase 3 RxPONDER trial compared endocrine therapy (ET) alone or with chemotherapy (CET) … A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial." }, "effect": { "measure": "HR", "value": 0.6, "ci_low": 0.43, "ci_high": 0.83, "ci_level": "95%", "p": "0.002", "endpoint": "Invasive disease-free survival, premenopausal women (prespecified separate analysis after menopausal-status interaction P = 0.008); postmenopausal HR 1.02 (95% CI 0.82 to 1.26; P = 0.89)", "quote": "Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002)" }, "landmark": [ { "endpoint": "Invasive disease-free survival (premenopausal women)", "timepoint": "5 years", "experimental_pct": 93.9, "control_pct": 89, "higher_is_better": true, "experimental_arm": "Chemoendocrine therapy", "control_arm": "Endocrine therapy only", "quote": "Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy", "difference_pp": 4.9, "nnt": 21, "quote_note": "primary report, NEJM 2021, third interim analysis" }, { "endpoint": "Invasive disease-free survival (postmenopausal women)", "timepoint": "5 years", "experimental_pct": 91.3, "control_pct": 91.9, "higher_is_better": true, "experimental_arm": "Chemoendocrine therapy", "control_arm": "Endocrine therapy only", "quote": "Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit", "difference_pp": -0.6, "nnt": null, "nnt_label": "favours control", "quote_note": "primary report, NEJM 2021, third interim analysis", "nnh": 167 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In women with HR-positive, HER2-negative breast cancer, 1 to 3 positive nodes and a recurrence score of 25 or lower, adding chemotherapy to endocrine therapy raised 5-year invasive disease-free survival from 89.0% to 93.9% in premenopausal women (HR 0.60) but not in postmenopausal women (91.3% vs 91.9%; HR 1.02). A later biomarker analysis in women under 55 found the benefit confined to those with AMH ≥10 pg/ml, and neither abstract reports chemotherapy toxicity, so the harm side of the trade-off cannot be quantified from these sources.", "takeaway_ko": "호르몬수용체 양성, HER2 음성이며 액와림프절 전이 1~3개, 재발점수 25 이하인 유방암 여성에서 내분비요법에 항암화학요법을 추가했을 때, 폐경 전 여성에서는 5년 침습적 무병생존율이 89.0%에서 93.9%로 높아졌으나(HR 0.60), 폐경 후 여성에서는 차이가 없었습니다(91.3% 대 91.9%, HR 1.02). 이후 55세 미만 여성 대상 바이오마커 분석에서는 AMH 10 pg/ml 이상인 환자에서만 이득이 확인되었으며, 두 초록 모두 항암화학요법 독성을 보고하지 않아 위해 측면은 이 자료로 정량화할 수 없습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TAILORx", "trial": "B-TAILORx", "papers": [ { "key": "P-TAILORx", "pmid": "29860917", "title": "Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.", "journal": "N Engl J Med", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29860917/", "doi": "10.1056/NEJMoa1804710", "errata": [] }, { "key": "P-TAILORxRisk", "pmid": "31157962", "title": "Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.", "journal": "N Engl J Med", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31157962/", "doi": "10.1056/NEJMoa1904819", "errata": [] }, { "key": "P-TAILORxLate", "pmid": "39041867", "title": "Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival.", "journal": "NEJM Evid", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39041867/", "doi": "10.1056/EVIDoa2300267", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "The randomized result does not establish chemotherapy omission for every younger woman or for scores outside 11-25. Lower- and higher-score groups received assigned treatment without the same randomized comparison. The 2019 clinical-risk analysis added prognostic information from tumor size and grade. The 2024 report incorporated extended TAILORx follow-up into a multi-trial RSClin model and evaluated prognosis in a separate registry; that model validation is distinct from a new randomized treatment comparison. Late recurrence prognosis does not itself prove benefit from a particular extended endocrine regimen. Invasive DFS includes second primary cancers and death, so it should not be presented as distant recurrence alone.", "program": "breast", "kind": "rct", "level": "clinical", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "TAILORx", "result": "mixed", "setting": "Adjuvant endocrine therapy with or without chemotherapy for an intermediate 21-gene recurrence score", "population": "Women with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer; the randomized comparison was restricted to recurrence scores of 11-25", "claim": "Of 10273 enrolled women, 9719 were eligible and had follow-up, and 6711 with scores of 11-25 entered the randomized comparison. The primary report found endocrine therapy alone noninferior for invasive DFS (HR for endocrine versus chemoendocrine therapy 1.08, 95% CI 0.94-1.24). At nine years, invasive DFS was 83.3% vs 84.3%, freedom from distant recurrence 94.5% vs 95.0%, and overall survival 93.9% vs 93.8%. Exploratory treatment effects varied with age and score; some chemotherapy benefit was seen in women aged 50 or younger with scores of 16-25.", "trialRecord": { "key": "B-TAILORx", "nct": "NCT00310180", "acronym": "TAILORx", "title": "Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 10273, "sponsor": "National Cancer Institute (NCI)", "sponsorClass": "NIH", "collaborators": [ "American College of Surgeons", "Cancer and Leukemia Group B", "NSABP Foundation Inc", "NCIC Clinical Trials Group", "North Central Cancer Treatment Group", "SWOG Cancer Research Network" ], "hasResults": true, "start": "2006-04-07", "lastUpdate": "2026-10-01", "url": "https://clinicaltrials.gov/study/NCT00310180" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive disease-free survival (freedom from invasive disease recurrence, second primary cancer, or death); noninferiority of endocrine therapy alone", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": 6711, "assessment": "not stated", "quote": "We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death)." }, "effect": { "measure": "HR", "value": 1.08, "ci_low": 0.94, "ci_high": 1.24, "ci_level": "95%", "p": "P=0.26", "endpoint": "Invasive disease-free survival (endocrine therapy alone vs chemoendocrine therapy; HR >1 favors chemoendocrine therapy); noninferiority met", "quote": "Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26)." }, "landmark": [ { "endpoint": "Invasive disease-free survival", "timepoint": "9 years", "experimental_pct": 83.3, "control_pct": 84.3, "higher_is_better": true, "experimental_arm": "Endocrine therapy alone", "control_arm": "Chemoendocrine therapy", "quote": "At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group)", "difference_pp": -1, "nnt": null, "nnt_label": "favours control", "quote_note": "P-TAILORx, NEJM 2018; the later papers do not report updated arm-level comparisons", "nnh": 100 }, { "endpoint": "Freedom from distant recurrence", "timepoint": "9 years", "experimental_pct": 94.5, "control_pct": 95, "higher_is_better": true, "experimental_arm": "Endocrine therapy alone", "control_arm": "Chemoendocrine therapy", "quote": "At 9 years, the two treatment groups had similar rates of … freedom from disease recurrence at a distant site (94.5% and 95.0%)", "difference_pp": -0.5, "nnt": null, "nnt_label": "favours control", "quote_note": "P-TAILORx, NEJM 2018", "nnh": 200 }, { "endpoint": "Freedom from distant or local-regional recurrence", "timepoint": "9 years", "experimental_pct": 92.2, "control_pct": 92.9, "higher_is_better": true, "experimental_arm": "Endocrine therapy alone", "control_arm": "Chemoendocrine therapy", "quote": "At 9 years, the two treatment groups had similar rates of … or at a distant or local-regional site (92.2% and 92.9%)", "difference_pp": -0.7, "nnt": null, "nnt_label": "favours control", "quote_note": "P-TAILORx, NEJM 2018", "nnh": 143 }, { "endpoint": "Overall survival", "timepoint": "9 years", "experimental_pct": 93.9, "control_pct": 93.8, "higher_is_better": true, "experimental_arm": "Endocrine therapy alone", "control_arm": "Chemoendocrine therapy", "quote": "At 9 years, the two treatment groups had similar rates of … and overall survival (93.9% and 93.8%)", "difference_pp": 0.1, "nnt": 1000, "quote_note": "P-TAILORx, NEJM 2018" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In women with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer and a 21-gene recurrence score of 11-25, endocrine therapy alone was compared with chemoendocrine therapy, and 9-year invasive disease-free survival was 83.3% vs 84.3%, with overall survival 93.9% vs 93.8% (HR 1.08, noninferiority met). Toxicity was not reported in these abstracts, so the harm trade-off of adding chemotherapy cannot be quantified here; an exploratory analysis found some chemotherapy benefit in women aged 50 or younger with scores of 16-25.", "takeaway_ko": "호르몬 수용체 양성, HER2 음성, 액와 림프절 음성 유방암이면서 21-유전자 재발점수가 11–25인 여성에서 내분비요법 단독과 항암화학요법 병용 내분비요법을 비교했습니다. 9년 침습적 무병생존율은 83.3% 대 84.3%, 전체생존율은 93.9% 대 93.8%였으며(HR 1.08, 비열등성 충족), 이 초록들에는 독성 자료가 보고되지 않아 항암화학요법 추가에 따른 위해를 정량화할 수 없습니다. 탐색적 분석에서는 50세 이하이면서 재발점수 16–25인 여성에서 항암화학요법의 일부 이득이 관찰되었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-MINDACT", "trial": "B-MINDACT", "papers": [ { "key": "P-MINDACT", "pmid": "27557300", "title": "70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.", "journal": "N Engl J Med", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27557300/", "doi": "10.1056/NEJMoa1602253", "errata": [] }, { "key": "P-MINDACT8y", "pmid": "33721561", "title": "70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33721561/", "doi": "10.1016/S1470-2045(21)00007-3", "errata": [] }, { "key": "P-MINDACTHighRisk", "pmid": "42762561", "title": "70-gene signature MammaPrint for early-stage HR-positive, HER2-negative breast cancer: Outcome in the MINDACT trial for key clinical-pathological high-risk subgroups.", "journal": "Eur J Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42762561/", "doi": "10.1016/j.ejca.2026.117044", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary benchmark evaluates the outcome without chemotherapy; meeting it does not establish identical outcomes between treatment groups. The randomized long-term comparison still showed a chemotherapy advantage. Age analyses were underpowered and exploratory within hormone receptor-positive, HER2-negative disease, with wide uncertainty around absolute differences; they do not validate age alone as an omission rule. Chemotherapy-induced ovarian suppression is a proposed explanation, not a randomized mechanistic finding. The later high-risk-feature analysis again used a selected older subgroup and does not convert small subgroup differences into proof of no benefit. These reports are one trial, and the overall eligibility population was not restricted to hormone receptor-positive, HER2-negative disease.", "program": "breast", "kind": "rct", "level": "clinical", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "MINDACT", "result": "mixed", "setting": "Clinical and 70-gene risk assessment to inform adjuvant chemotherapy in early breast cancer", "population": "Women with operable early breast cancer and up to three positive nodes; chemotherapy allocation was randomized when clinical and genomic risk classifications disagreed", "claim": "The trial enrolled 6693 patients. At updated follow-up, the primary test population, patients at high clinical risk and low genomic risk who adhered to no chemotherapy, comprised 644 patients; their five-year distant metastasis-free survival was 95.1% (95% CI 93.1-96.6), exceeding the prespecified 92% lower-bound benchmark. In the separate intention-to-treat comparison, 749 patients were allocated to chemotherapy and 748 to no chemotherapy. Eight-year distant metastasis-free survival was 92.0% vs 89.4% (HR 0.66, 95% CI 0.48-0.92).", "trialRecord": { "key": "B-MINDACT", "nct": "NCT00433589", "acronym": "MINDACT", "title": "Genetic Testing or Clinical Assessment in Determining the Need for Chemotherapy in Women With Breast Cancer That Involves No More Than 3 Lymph Nodes", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 6600, "sponsor": "European Organisation for Research and Treatment of Cancer - EORTC", "sponsorClass": "NETWORK", "collaborators": [ "Agendia", "Breast International Group", "Roche Pharma AG", "Novartis", "Sanofi" ], "hasResults": false, "start": "2007-02", "lastUpdate": "2022-11-17", "url": "https://clinicaltrials.gov/study/NCT00433589" }, "sources": 4, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "5-year distant metastasis-free survival in patients with high clinical risk and low genomic risk who did not receive chemotherapy, tested against a predefined non-inferiority lower 95% CI boundary of 92%", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. … Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. … Treatment allocation was not masked. … Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population." }, "effect": { "measure": "HR", "value": 0.66, "ci_low": 0.48, "ci_high": 0.92, "ci_level": "95%", "p": null, "endpoint": "8-year distant metastasis-free survival, chemotherapy vs no chemotherapy, intention-to-treat population of high clinical/low genomic risk patients (Lancet Oncol 2021 update)", "quote": "The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92)." }, "landmark": [ { "endpoint": "Distant metastasis-free survival (intention-to-treat, high clinical/low genomic risk)", "timepoint": "8 years", "experimental_pct": 92, "control_pct": 89.4, "higher_is_better": true, "experimental_arm": "Chemotherapy", "control_arm": "No chemotherapy", "quote": "The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92).", "difference_pp": 2.6, "nnt": 39, "quote_note": "Lancet Oncol 2021 update (most recent report of this comparison; median follow-up 8·7 years" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": null }, "takeaway_en": "In women with operable early breast cancer and up to three positive nodes who were high clinical risk but low 70-gene genomic risk, adjuvant chemotherapy was randomly compared with no chemotherapy. At 8 years, distant metastasis-free survival was 92.0% with chemotherapy versus 89.4% without (a 2.6 percentage-point difference; HR 0.66), and the patients who skipped chemotherapy had 5-year distant metastasis-free survival of 95.1%; chemotherapy toxicity was not reported in these abstracts.", "takeaway_ko": "수술 가능한 조기 유방암으로 액와림프절 전이가 3개 이하이면서, 임상적 위험도는 높고 70-유전자 유전체 위험도는 낮은 여성을 대상으로 보조 항암화학요법 시행군과 비시행군을 무작위 배정하여 비교하였습니다. 8년 원격전이 무병생존율은 항암화학요법군 92.0%, 비시행군 89.4%로 2.6%p 차이를 보였고(HR 0.66), 항암화학요법을 생략한 환자의 5년 원격전이 무병생존율은 95.1%였으며, 항암화학요법의 독성은 이 초록들에 보고되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-SALSA", "trial": "B-SALSA", "papers": [ { "key": "P-SALSA", "pmid": "34320285", "title": "Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer.", "journal": "N Engl J Med", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34320285/", "doi": "10.1056/NEJMoa2104162", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The comparison concerns seven versus ten total years of endocrine therapy, not initial treatment versus no treatment. The primary analysis began after two years of extension and does not represent all randomized women from randomization. DFS combines recurrence, new cancers and death; it is not distant recurrence alone. A nonsignificant superiority result does not establish equivalence or rule out benefit for every individual. Subgroup findings do not establish a validated rule for selecting longer treatment. HER2-negative status was not required. Fracture and efficacy results have distinct outcome definitions and analysis windows.", "program": "breast", "kind": "rct", "level": "clinical", "by": "Codex (GPT-6)", "added": "2026-09-30", "label": "ABCSG-16/SALSA", "result": "negative", "setting": "Two versus five additional years of anastrozole after five years of endocrine therapy", "population": "Postmenopausal women with hormone receptor-positive, nonmetastatic breast cancer after prior adjuvant endocrine therapy", "claim": "Of 3484 enrolled women, 3208 were still participating and free of progression after the first two years; they formed the population for the primary landmark analysis. With anastrozole extended for five rather than two years, there were 335 progression-or-death events in each group (HR 0.99, 95% CI 0.85-1.15; P = .90), and no DFS improvement was demonstrated. Clinical fracture risk was higher with the longer extension (HR 1.35, 95% CI 1.00-1.84).", "trialRecord": { "key": "B-SALSA", "nct": "NCT00295620", "acronym": "SALSA", "title": "Secondary Adjuvant Long Term Study With Arimidex", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 3484, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2004-03-01", "lastUpdate": "2019-10-02", "url": "https://clinicaltrials.gov/study/NCT00295620" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival (primary analysis in patients still participating and recurrence-free 2 years after randomization)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 3484, "assessment": "not stated", "quote": "In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). … Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years" }, "effect": { "measure": "HR", "value": 0.99, "ci_low": 0.85, "ci_high": 1.15, "ci_level": "95%", "p": "0.90", "endpoint": "Disease-free survival (disease progression or death), 5-year vs 2-year extension, primary-analysis set at 8 years", "quote": "Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84)." }, "takeaway_en": "In postmenopausal women with hormone receptor-positive breast cancer who had completed 5 years of adjuvant endocrine therapy, this trial compared an additional 5 years with an additional 2 years of anastrozole. Disease-free survival did not differ (335 events in each group; HR 0.99, 95% CI 0.85-1.15), and the longer extension carried a higher risk of clinical bone fracture (HR 1.35, 95% CI 1.00-1.84).", "takeaway_ko": "5년간 보조 내분비요법을 마친 호르몬 수용체 양성 폐경 후 유방암 여성을 대상으로, 아나스트로졸을 5년 추가 투여하는 군과 2년 추가 투여하는 군을 비교하였다. 무병생존율에는 차이가 없었으며(양군 각 335건의 사건; HR 0.99, 95% CI 0.85-1.15), 5년 연장군에서 임상적 골절 위험이 더 높았다(HR 1.35, 95% CI 1.00-1.84).", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DAISY", "trial": "B-DAISY", "papers": [ { "key": "P-DAISY", "pmid": "37488289", "title": "Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial.", "journal": "Nat Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37488289/", "doi": "10.1038/s41591-023-02478-2", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "Nonrandomized, with no randomized between-cohort or chemotherapy comparator. The retrieved abstract and registry snapshot do not provide HR-stratified IHC0 efficacy or distinguish no-staining IHC0 from ultralow membrane staining, so they cannot resolve the three HR-specific empty matrix cells. Enrolled and full-analysis-set denominators differ. Small exploratory biopsy correlations do not establish a mechanism or a treatment-selection rule.", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "mixed", "setting": "Multicenter open-label phase 2 DS-8201a monotherapy for metastatic breast cancer", "population": "HER2-overexpressing, HER2-low and HER2 IHC0 metastatic breast cancer", "claim": "The single-arm phase 2 DAISY trial enrolled 72 patients with HER2-overexpressing, 74 with HER2-low and 40 with HER2 IHC0 metastatic breast cancer (efficacy full analysis set, n=177). Confirmed ORR was 70.6% (95% CI 58.3-81) in cohort 1, 37.5% (26.4-49.7) in cohort 2, and 29.7% (15.9-47) in cohort 3. The primary endpoint was met in cohorts 1 and 2 only. The authors reported no new safety signals.", "by": "Muse Spark1.3", "added": "2026-09-30", "label": "DAISY", "trialRecord": { "key": "B-DAISY", "nct": "NCT04132960", "acronym": "DAISY", "title": "Study of DS-8201a, an Antibody Drug Conjugate for Advanced Breast Cancer Patients, With Biomarkers Analysis", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 186, "sponsor": "UNICANCER", "sponsorClass": "OTHER", "collaborators": [ "Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company" ], "hasResults": false, "start": "2019-10-21", "lastUpdate": "2025-06-12", "url": "https://clinicaltrials.gov/study/NCT04132960" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-AVAGAST", "trial": "G-AVAGAST", "papers": [ { "key": "P-AVAGAST", "pmid": "21844504", "title": "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study.", "journal": "J Clin Oncol", "year": "2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21844504/", "doi": "10.1200/JCO.2011.36.2236", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Regional subgroup differences were preplanned but exploratory and do not establish efficacy. Safety from primary abstract: most common grade 3-5 events neutropenia, anemia, decreased appetite; no new bevacizumab signal identified. Commentaries without abstracts remain full-text-unread and are not evidence of correction.", "label": "AVAGAST", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "First line", "population": "Advanced gastric or gastro-oesophageal junction adenocarcinoma", "claim": "The randomized, double-blind, placebo-controlled phase 3 AVAGAST trial (n=774) of bevacizumab plus fluoropyrimidine-cisplatin versus placebo plus fluoropyrimidine-cisplatin as first-line therapy for advanced gastric cancer did not meet its primary endpoint: median overall survival was 12.1 vs 10.1 months (HR 0.87; 95% CI 0.73-1.03; P=.1002; 517 deaths). Median progression-free survival (6.7 vs 5.3 months; HR 0.80; 95% CI 0.68-0.93; P=.0037) and response rate (46.0% vs 37.4%; P=.0315), both secondary endpoints, were higher with bevacizumab but do not overturn the negative primary result.", "by": "Muse Spark1.3", "added": "2026-09-30", "trialRecord": { "key": "G-AVAGAST", "nct": "NCT00548548", "acronym": "AVAGAST", "title": "A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-line Therapy in Patients With Advanced Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 774, "sponsor": "Genentech, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Hoffmann-La Roche", "Chugai Pharmaceutical" ], "hasResults": true, "start": "2007-09", "lastUpdate": "2017-06-14", "url": "https://clinicaltrials.gov/study/NCT00548548" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 774, "assessment": "not stated", "quote": "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. … In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed." }, "effect": { "measure": "HR", "value": 0.87, "ci_low": 0.73, "ci_high": 1.03, "ci_level": "95%", "p": ".1002", "endpoint": "Overall survival", "quote": "Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002)." }, "landmark": [ { "endpoint": "Overall response rate (secondary)", "timepoint": "not stated (best overall response)", "experimental_pct": 46, "control_pct": 37.4, "higher_is_better": true, "experimental_arm": "Bevacizumab plus fluoropyrimidine-cisplatin", "control_arm": "Placebo plus fluoropyrimidine-cisplatin", "quote": "overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo", "difference_pp": 8.6, "nnt": 12, "quote_note": "P-AVAGAST, J Clin Oncol 2011, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified." }, "takeaway_en": "In 774 patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma, adding bevacizumab to fluoropyrimidine-cisplatin did not significantly improve overall survival, the primary endpoint (median 12.1 vs 10.1 months; HR 0.87, 95% CI 0.73 to 1.03; P = .1002). Response rate (46.0% vs 37.4%) and progression-free survival were higher with bevacizumab, but these were secondary endpoints. Common grade 3 to 5 toxicities were similar between arms (neutropenia 35% vs 37%), and no new bevacizumab safety signals were identified.", "takeaway_ko": "치료 경험이 없는 진행성 위암 또는 위식도접합부 선암 환자 774명에서 플루오로피리미딘-시스플라틴에 베바시주맙을 추가해도 일차 평가변수인 전체생존기간은 유의하게 개선되지 않았습니다(중앙값 12.1개월 대 10.1개월; 위험비 0.87, 95% 신뢰구간 0.73–1.03; P = .1002). 반응률(46.0% 대 37.4%)과 무진행생존기간은 베바시주맙군에서 더 높았으나, 이는 이차 평가변수입니다. 주요 3–5등급 이상반응은 두 군 간 비슷했으며(호중구감소증 35% 대 37%), 베바시주맙 관련 새로운 안전성 신호는 확인되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ATTR4", "trial": "G-ATTR4", "papers": [ { "key": "P-ATTR4", "pmid": "35030335", "title": "Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.", "journal": "Lancet Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35030335/", "doi": "10.1016/S1470-2045(21)00692-6", "errata": [] }, { "key": "P-ATTR4Long", "pmid": "39162872", "title": "Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial.", "journal": "Gastric Cancer", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39162872/", "doi": "10.1007/s10120-024-01535-0", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "G-HER2NEG" ], "limits": "PFS benefit does not reverse OS failure; OS landmark trends and complete-responder survival are post hoc survivor-conditioned and exploratory per Methods, not proof of cure or an overall OS benefit. Population limited to Asian sites, ECOG 0-1, measurable disease, PD-L1 unselected. Primary-report harms: treatment-related serious events 88/359 (25%) vs 51/358 (14%); six treatment-related deaths, three per arm; no new late signals at 3 years.", "label": "ATTRACTION-4", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First line", "population": "HER2-negative untreated unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer", "claim": "The randomized, multicentre, double-blind, placebo-controlled phase 2-3 ATTRACTION-4 trial (n=724; Japan/South Korea/Taiwan; SOX/CAPOX backbone) compared nivolumab plus chemotherapy with placebo plus chemotherapy in untreated, HER2-negative, unresectable advanced or recurrent gastric/GEJ cancer. Of the initial co-primary endpoints, centrally assessed PFS improved (median 10.45 vs 8.34 months; HR 0.68; 98.51% CI 0.51-0.90; p=0.0007; Oct 2018), whereas OS did not (median 17.45 vs 17.15 months; HR 0.90; 95% CI 0.75-1.08; p=0.26; Jan 2020). At 3-year follow-up (May 2021), median PFS was 10.94 vs 8.48 months (HR 0.67; 95% CI 0.55-0.82), and median OS was unchanged at 17.45 vs 17.15 months (HR 0.89; 95% CI 0.75-1.05).", "by": "Muse Spark1.3", "added": "2026-09-30", "trialRecord": { "key": "G-ATTR4", "nct": "NCT02746796", "acronym": null, "title": "Study of ONO-4538 in Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 680, "sponsor": "Ono Pharmaceutical Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2016-03", "lastUpdate": "2024-05-03", "url": "https://clinicaltrials.gov/study/NCT02746796" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Co-primary endpoints: centrally assessed progression-free survival and overall survival in the intention-to-treat population", "primary_endpoint_type": "PFS", "design": { "phase": "2/3", "randomized": true, "blinding": "double-blind", "n_randomized": 724, "assessment": "not stated", "quote": "We did a randomised, multicentre, double-blind, placebo-controlled, phase 2-3 trial (ATTRACTION-4) … The primary endpoints were centrally assessed progression-free survival and overall survival in the intention-to-treat population … 724 patients were randomly assigned to treatment: 362 patients to the nivolumab plus chemotherapy group and 362 to the placebo plus chemotherapy group." }, "effect": { "measure": "HR", "value": 0.67, "ci_low": 0.55, "ci_high": 0.82, "ci_level": "95%", "p": null, "endpoint": "Centrally assessed progression-free survival (3-year follow-up, cutoff May 10, 2021)", "quote": "PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55-0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75-1.05)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Six treatment-related deaths: three in the nivolumab plus chemotherapy group (febrile neutropenia, hepatic failure, sudden death) and three in the placebo plus chemotherapy group (sepsis, haemolytic anaemia, interstitial lung disease)", "quote": "Treatment-related serious adverse events of any grade were observed in 88 (25%) patients in the nivolumab plus chemotherapy group and in 51 (14%) in the placebo plus chemotherapy group … Six treatment-related deaths occurred: three in the nivolumab plus chemotherapy group (one each of febrile neutropenia, hepatic failure, and sudden death) and three in the placebo plus chemotherapy group (one each of sepsis, haemolytic anaemia, and interstitial lung disease)." }, "takeaway_en": "In Asian patients with untreated HER2-negative unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer, adding nivolumab to SOX or CAPOX chemotherapy prolonged centrally assessed progression-free survival at 3-year follow-up (median 10.94 vs. 8.48 months; HR 0.67, 95% CI 0.55-0.82), but overall survival did not differ (median 17.45 vs. 17.15 months; HR 0.89). Treatment-related serious adverse events were more frequent with nivolumab (25% vs 14%), and treatment-related deaths were three in each group.", "takeaway_ko": "HER2 음성, 치료 경험이 없는 절제 불가능한 진행성 또는 재발성 위암·위식도접합부암 아시아인 환자에서 SOX 또는 CAPOX 항암화학요법에 니볼루맙을 추가하자, 3년 추적 시점에 중앙 평가 무진행생존기간이 연장되었습니다(중앙값 10.94개월 대 8.48개월; HR 0.67, 95% CI 0.55-0.82). 그러나 전체생존기간에는 차이가 없었습니다(중앙값 17.45개월 대 17.15개월; HR 0.89). 치료 관련 중대한 이상반응은 니볼루맙군에서 더 많았고(25% 대 14%), 치료 관련 사망은 양군 각각 3명이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-SUNLIGHT", "trial": "C-SUNLIGHT", "papers": [ { "key": "P-SUNLIGHT", "pmid": "37133585", "title": "Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37133585/", "doi": "10.1056/NEJMoa2214963", "errata": [] }, { "key": "P-SUNLIGHTQoL", "pmid": "39818468", "title": "Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.", "journal": "Clin Colorectal Cancer", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39818468/", "doi": "10.1016/j.clcc.2024.12.002", "errata": [] }, { "key": "P-SUNLIGHTKRAS", "pmid": "38471240", "title": "Impact of KRAS(G12) mutations on survival with trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer: post hoc analysis of the phase III SUNLIGHT trial.", "journal": "ESMO Open", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38471240/", "doi": "10.1016/j.esmoop.2024.102945", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label, limited to ECOG PS 0-1 and at most two prior chemotherapy regimens. KRAS analyses are exploratory and do not establish a predictive interaction. QoL scores remained stable while definitive deterioration was delayed; maintained-performance analyses select a subgroup. Published correspondence was unread in full text.", "label": "SUNLIGHT", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Refractory metastatic colorectal cancer after maximum two prior chemotherapy regimens", "population": "Adults with refractory metastatic colorectal cancer, ECOG PS 0-1, previously treated with no more than two prior regimens", "claim": "In the phase 3 SUNLIGHT trial (NCT04737187; 246 per group), trifluridine-tipiracil (FTD-TPI) plus bevacizumab significantly improved overall survival versus FTD-TPI monotherapy in refractory metastatic colorectal cancer (median OS 10.8 vs 7.5 months; HR 0.61, 95% CI 0.49-0.77; P<0.001). Progression-free survival was also improved (median 5.6 vs 2.4 months; HR 0.44, 95% CI 0.36-0.54; P<0.001), as was time to ECOG performance-status worsening to >=2 (median 9.3 vs 6.3 months; HR 0.54, 95% CI 0.43-0.67). The most common adverse events were neutropenia, nausea, and anemia; no treatment-related deaths occurred. Post hoc KRAS G12 subgroup results and a separate quality-of-life analysis from this trial are also linked here.", "by": "Gemini Flash3.8", "added": "2026-09-30", "trialRecord": { "key": "C-SUNLIGHT", "nct": "NCT04737187", "acronym": "SUNLIGHT", "title": "Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 492, "sponsor": "Taiho Oncology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Institut de Recherches Internationales Servier" ], "hasResults": true, "start": "2020-11-25", "lastUpdate": "2024-09-24", "url": "https://clinicaltrials.gov/study/NCT04737187" }, "sources": 4, "corrections": 0, "analysisRecord": null }, { "id": "U-TRIBE2", "trial": "C-TRIBE2", "papers": [ { "key": "P-TRIBE2", "pmid": "32164906", "title": "Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial.", "journal": "Lancet Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32164906/", "doi": "10.1016/S1470-2045(19)30862-9", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label strategy design without masking. Primary endpoint was strategy-specific PFS2, not OS or first-line PFS; this record does not summarize an updated OS analysis. Triplet intensification increased serious and fatal toxicities. Unposted registry results do not indicate trial data absence. Published correspondence was unread in full text.", "label": "TRIBE2", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First-line and second-line strategy for unresectable metastatic colorectal cancer", "population": "Adults with previously untreated unresectable metastatic colorectal cancer, aged 18-70 years with ECOG PS 0-2 or aged 71-75 years with ECOG PS 0", "claim": "In the phase 3 TRIBE2 trial (NCT02339116, n=679; 339 experimental vs 340 control), upfront FOLFOXIRI plus bevacizumab with reintroduction after progression significantly improved the primary endpoint of progression-free survival 2 (PFS2, defined as time from randomization to disease progression on any post-first-progression treatment, or death) compared with sequential mFOLFOX6-bevacizumab then FOLFIRI-bevacizumab (median PFS2 19.2 vs 16.4 months; HR 0.74, 95% CI 0.63-0.88; p=0.0005). First-line serious adverse events occurred in 84 (25%) of 339 versus 56 (17%) of 340 patients, with higher grade 3-4 diarrhea (17% vs 5%) and neutropenia (50% vs 21%), and lower hypertension (7% vs 10%). Treatment-related deaths during first-line therapy numbered 8 versus 4. Toxic deaths after progression numbered 3 versus 4.", "by": "Gemini Flash3.8", "added": "2026-09-30", "trialRecord": { "key": "C-TRIBE2", "nct": "NCT02339116", "acronym": "TRIBE2", "title": "Folfoxiri Plus Bev Followed by Reintroduction of Folfoxiri Plus Bev at Progression Versus Folfox Plus Bev Followed by Folfiri Plus Bev in mCRC", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 654, "sponsor": "Gruppo Oncologico del Nord-Ovest", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2015-02-26", "lastUpdate": "2020-02-05", "url": "https://clinicaltrials.gov/study/NCT02339116" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CIRCULATE-AIO", "trial": "C-CIRCULATE-AIO", "papers": [ { "key": "P-CIRCULATE-AIO", "pmid": "42225236", "title": "Chemotherapy for patients with circulating tumour DNA-positive, stage II colon cancer (CIRCULATE)-an AIO/ABCSG trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42225236/", "doi": "10.1016/j.annonc.2026.05.001", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Early funding closure left the ctDNA-positive randomized comparison very small, with 26 assigned to CHEMO and 81% starting therapy, limiting power. All differences used one-sided log-rank tests. Per-protocol analysis excluded untreated CHEMO patients and is selected; it cannot replace ITT. The 287 OBS group comprises all observation assignments, not a ctDNA-positive subgroup. Results apply to the academic tumour-informed NGS assay in stage II pMMR/MSS colon cancer, not to other CIRCULATE studies or other stages and assays. Recurrence and DFS are separate endpoints. The registry was last updated in 2020 and retains estimated enrolment; the 2026 publication reports actual trial results.", "label": "CIRCULATE AIO/ABCSG", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Postoperative adjuvant setting for stage II colon cancer in Germany and Austria", "population": "UICC stage II, mismatch repair proficient/microsatellite stable colon cancer with postoperative ctDNA result; primary treatment comparison in ctDNA-positive patients randomized to capecitabine with or without oxaliplatin versus observation", "claim": "In ctDNA-positive stage II pMMR/MSS colon cancer, capecitabine with or without oxaliplatin did not demonstrate a DFS benefit versus observation in the primary ITT analysis: 3-year DFS 61% versus 38% (HR 0.55, 95% CI 0.21–1.48; one-sided P = 0.12). This is a failure to demonstrate benefit, not proof of no benefit. ctDNA positivity was associated with worse DFS and OS than ctDNA negativity; that prognostic association is distinct from treatment efficacy.", "by": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "C-CIRCULATE-AIO", "nct": "NCT04089631", "acronym": "CIRCULATE", "title": "Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 4812, "sponsor": "Technische Universität Dresden", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2020-06-26", "lastUpdate": "2020-08-06", "url": "https://clinicaltrials.gov/study/NCT04089631" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-DB08", "trial": "B-DB08", "papers": [ { "key": "P-DB08", "pmid": "41504632", "title": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer.", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41504632/", "doi": "10.1158/1078-0432.CCR-25-0874", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2LOW-B" ], "subtypes": [], "limits": "Non-randomized, open-label modular trial; response rates are descriptive and non-comparative across modules due to disparate hormone receptor eligibility and prior therapy lines. T-DXd plus durvalumab plus paclitaxel was not pursued beyond dose-finding for strategic reasons (n=3). Adjudicated drug-related ILD/pneumonitis occurred in 3/20 capecitabine-treated patients (two grade 2, one fatal grade 5), 8/40 capivasertib-treated patients (grade ≤2), and 5/20 fulvestrant-treated patients (grade 2); The abstract does not report ILD incidence for anastrozole, so zero incidence is not inferred. Findings cannot be generalized to HER2-ultralow or HER2-zero disease.", "label": "DESTINY-Breast08", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "metastatic", "population": "Patients with locally confirmed HER2-low (IHC 1+ or IHC 2+/ISH-) metastatic breast cancer with cohort-specific hormone receptor status requirements", "claim": "In the dose-expansion part of the phase Ib DESTINY-Breast08 trial (n=101), trastuzumab deruxtecan combinations showed preliminary antitumor activity in HER2-low metastatic breast cancer. Investigator-assessed objective response rates were 60% with capecitabine (n=20), 60% with capivasertib (n=40), 71.4% with anastrozole (n=21), and 40% with fulvestrant (n=20). Grade ≥3 adverse events occurred in 55% (11/20) of patients with the capecitabine combination, 67.5% (27/40) with capivasertib, 47.6% (10/21) with anastrozole, and 55% (11/20) with fulvestrant.", "by": "Gemini Flash3.8; reviewed by Muse Spark1.3; integrated by Codex (GPT-6)", "added": "2026-09-30", "trialRecord": { "key": "B-DB08", "nct": "NCT04556773", "acronym": "DB-08", "title": "A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1" ], "enrollment": 138, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo Co., Ltd.", "Daiichi Sankyo Company, Limited" ], "hasResults": false, "start": "2020-12-17", "lastUpdate": "2026-08-03", "url": "https://clinicaltrials.gov/study/NCT04556773" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-RINDBeRG", "trial": null, "papers": [ { "key": "P-RINDBeRG", "pmid": "40408613", "title": "Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial.", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40408613/", "doi": "10.1200/JCO.24.01119", "errata": [] }, { "key": "P-RINDBeRGAge", "pmid": "41343125", "title": "Efficacy and safety of irinotecan-based therapy in elderly patients with advanced gastric cancer receiving third-line or later chemotherapy: post-hoc age-subgroup analysis of the rindberg trial.", "journal": "Gastric Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41343125/", "doi": "10.1007/s10120-025-01692-w", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "The primary OS endpoint was not met; this is not proof of zero effect. Hazard ratios and P values are omitted because the PubMed abstract, journal body/figures and registry report differing values without a verified correction resolving them. Only concordant medians and endpoint conclusions are summarized. The efficacy full analysis set, randomized population and safety population have different denominators; they must not be treated as interchangeable. Open-label, Japan-only enrollment selected patients by performance status and excluded prior irinotecan. Fatal pulmonary infections occurred in both arms, and several toxicities were more frequent with combination therapy; manageable does not mean harmless. Post-hoc age comparisons do not support extrapolation to frail older patients. The linked 2026 comment (PMID 41632403) is subscription-only and unread, and is not treated as a formal correction. The registry is jRCTs051180187, transferred from UMIN000023065.", "label": "RINDBeRG · ramucirumab beyond progression", "registry": { "system": "jRCT", "id": "jRCTs051180187", "url": "https://jrct.mhlw.go.jp/en-latest-detail/jRCTs051180187" }, "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Third or later line after progression on ramucirumab-containing chemotherapy", "population": "Advanced or recurrent gastric/GEJ adenocarcinoma in Japan", "by": "Muse Spark1.3", "added": "2026-09-30", "claim": "In 402 randomized patients in Japan with advanced gastric/GEJ adenocarcinoma progressing during ramucirumab-containing chemotherapy, ramucirumab plus irinotecan as third-or-later-line treatment did not show a statistically significant overall survival advantage over irinotecan alone (median 9.4 vs 8.5 months), despite improved progression-free survival (median 3.8 vs 2.8 months) and reported disease control. Efficacy was analyzed in a full analysis set excluding patients found ineligible after randomization. A post hoc analysis by age found no statistically significant OS or PFS differences between older and younger participants within either treatment arm; this does not establish equivalence between age groups.", "reviewedBy": "Gemini Flash3.8", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 402, "assessment": "not stated", "quote": "Between February 2017 and August 2022, 402 patients in Japan were randomly assigned to receive ramucirumab plus irinotecan (n = 202) or irinotecan monotherapy (n = 200)." }, "effect": { "measure": "HR", "value": 0.91, "ci_low": 0.74, "ci_high": 1.12, "ci_level": "95%", "p": ".49", "endpoint": "Overall survival (adjusted HR)", "quote": "The median OS was 9.4 months in the combination arm and 8.5 months in the monotherapy arm, with an adjusted HR of 0.91 (95% CI, 0.74 to 1.12; P = .49)." }, "landmark": [ { "endpoint": "Disease control rate", "timepoint": "best response during treatment", "experimental_pct": 64.4, "control_pct": 52.1, "higher_is_better": true, "experimental_arm": "Ramucirumab plus irinotecan", "control_arm": "Irinotecan monotherapy", "quote": "the DCR was significantly better (64.4% v 52.1%; P = .03) with the combination therapy", "difference_pp": 12.3, "nnt": 9, "quote_note": "primary RINDBeRG report, J Clin Oncol 2025" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The adverse events of the combination therapy were manageable." }, "takeaway_en": "In 402 Japanese patients with advanced gastric or gastroesophageal cancer that progressed during ramucirumab-based chemotherapy, continuing ramucirumab with irinotecan as third- or later-line treatment did not significantly improve overall survival compared with irinotecan alone (median 9.4 vs 8.5 months; HR 0.91, 95% CI 0.74 to 1.12), although progression-free survival was longer (median 3.8 vs 2.8 months; HR 0.72) and disease control was higher (64.4% vs 52.1%). The abstract describes the combination's adverse events only as manageable and gives no grade 3 or higher or discontinuation rates; a post-hoc analysis reported comparable grade 3 or higher adverse events in patients aged 70 years or older and younger patients.", "takeaway_ko": "라무시루맙 기반 항암화학요법 중 진행한 일본인 진행성 위암 또는 위식도접합부암 환자 402명에서, 3차 이상 치료로 라무시루맙을 이리노테칸과 병용 지속했을 때 이리노테칸 단독 대비 전체생존기간이 유의하게 개선되지 않았습니다(중앙값 9.4개월 대 8.5개월; HR 0.91, 95% CI 0.74–1.12). 다만 무진행생존기간은 더 길었고(중앙값 3.8개월 대 2.8개월; HR 0.72) 질병조절률도 더 높았습니다(64.4% 대 52.1%). 초록에서는 병용요법의 이상반응을 '관리 가능한 수준'으로만 기술하며 3등급 이상 이상반응률이나 치료 중단율은 제시하지 않았습니다. 사후 분석에서는 70세 이상 고령 환자와 비고령 환자 간 3등급 이상 이상반응이 비슷했다고 보고했습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-OlympiAD", "trial": "B-OlympiAD", "papers": [ { "key": "P-OlympiAD", "pmid": "28578601", "title": "Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.", "journal": "N Engl J Med", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28578601/", "doi": "10.1056/NEJMoa1706450", "errata": [ { "pmid": "28792849", "title": "Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.", "url": "https://pubmed.ncbi.nlm.nih.gov/28792849/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-OlympiADOS", "pmid": "30689707", "title": "OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.", "journal": "Ann Oncol", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/30689707/", "doi": "10.1093/annonc/mdz012", "errata": [] }, { "key": "P-OlympiADLong", "pmid": "36893711", "title": "OlympiAD extended follow-up for overall survival and safety: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.", "journal": "Eur J Cancer", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36893711/", "doi": "10.1016/j.ejca.2023.01.031", "errata": [] } ], "pages": [], "targets": [ "PARP1" ], "biomarkers": [ "BM-gBRCA" ], "subtypes": [ "B-HRPOS", "B-TNBC" ], "limits": "Grade ≥3 adverse events occurred in 36.6% of patients receiving olaparib versus 50.5% with chemotherapy; treatment discontinuation rates due to toxic effects were 4.9% and 7.7%, respectively. Findings apply strictly to germline BRCA-mutated, HER2-negative metastatic breast cancer across hormone receptor-positive and triple-negative subtypes; they do not support extrapolation to somatic-only mutations, HRD all-comers, or early-stage adjuvant settings. OlympiAD is a distinct metastatic trial and must not be conflated with the adjuvant OlympiA trial; these metastatic results do not establish cure. The first-line overall survival subgroup finding is exploratory and does not establish overall survival benefit. Post-hoc extended follow-up does not represent independent prospective replication. The published erratum (PMID 28792849) supplied omitted print-edition author disclosures; that notice reports no efficacy or safety estimate correction. Linked commentary (PMID 29094857) has not been reviewed in full.", "label": "OlympiAD · olaparib in germline-BRCA metastatic breast cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Metastatic disease, up to two prior chemotherapy regimens for metastatic cancer", "population": "Germline BRCA1/2-mutated, HER2-negative metastatic breast cancer", "by": "Gemini Flash3.8", "added": "2026-09-30", "claim": "In the randomized phase 3 OlympiAD trial (NCT02000622), olaparib monotherapy was compared with single-agent chemotherapy of the physician's choice (capecitabine, eribulin or vinorelbine) in 302 patients with germline BRCA-mutated, HER2-negative metastatic breast cancer who had received up to two prior lines of chemotherapy for metastatic disease. In the intention-to-treat primary analysis assessed by blinded independent central review, olaparib significantly extended median progression-free survival compared to standard chemotherapy (7.0 months vs. 4.2 months; hazard ratio 0.58, 95% CI 0.43 to 0.80; P < 0.001), with an objective response rate of 59.9% versus 28.8%. In the planned final prespecified overall survival analysis (64% data maturity), median overall survival showed no statistically significant difference between olaparib and chemotherapy (19.3 months vs. 17.1 months; hazard ratio 0.90, 95% CI 0.66 to 1.23; P = 0.513). A subsequent post-hoc extended follow-up analysis (76.8% maturity) reported consistent overall survival findings (median 19.3 months vs. 17.1 months; hazard ratio 0.89, 95% CI 0.67 to 1.18).", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-OlympiAD", "nct": "NCT02000622", "acronym": "OlympiAD", "title": "Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 302, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Myriad Genetic Laboratories, Inc.", "Merck Sharp & Dohme LLC" ], "hasResults": true, "start": "2014-03-27", "lastUpdate": "2026-02-13", "url": "https://clinicaltrials.gov/study/NCT02000622" }, "sources": 4, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by blinded independent central review (intention-to-treat)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 302, "assessment": "blinded independent central review", "quote": "We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy … The primary end point was progression-free survival, which was assessed by blinded independent central review and was analyzed on an intention-to-treat basis. … Of the 302 patients who underwent randomization, 205 were assigned to receive olaparib and 97 were assigned to receive standard therapy." }, "effect": { "measure": "HR", "value": 0.58, "ci_low": 0.43, "ci_high": 0.8, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "Median progression-free survival was significantly longer in the olaparib group than in the standard-therapy group (7.0 months vs. 4.2 months; hazard ratio for disease progression or death, 0.58; 95% confidence interval, 0.43 to 0.80; P<0.001)." }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "Primary analysis", "experimental_pct": 59.9, "control_pct": 28.8, "higher_is_better": true, "experimental_arm": "Olaparib 300 mg twice daily", "control_arm": "Physician's-choice chemotherapy (capecitabine, eribulin, or vinorelbine)", "quote": "The response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group.", "difference_pp": 31.1, "nnt": 4, "quote_note": "P-OlympiAD, N Engl J Med 2017" }, { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 27.9, "control_pct": 21.2, "higher_is_better": true, "experimental_arm": "Olaparib 300 mg twice daily", "control_arm": "Physician's-choice chemotherapy (capecitabine, eribulin, or vinorelbine)", "quote": "Three-year survival was 27.9% for olaparib versus 21.2% for TPC.", "difference_pp": 6.7, "nnt": 15, "quote_note": "P-OlympiADLong, Eur J Cancer 2023, post-hoc extended follow-up, 76.8% maturity; most recent report" } ], "harms": { "grade3plus_experimental_pct": 36.6, "grade3plus_control_pct": 50.5, "discontinuation_experimental_pct": 4.9, "discontinuation_control_pct": 7.7, "treatment_related_deaths": null, "quote": "The rate of grade 3 or higher adverse events was 36.6% in the olaparib group and 50.5% in the standard-therapy group, and the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively." }, "takeaway_en": "In 302 patients with germline BRCA-mutated, HER2-negative metastatic breast cancer who had received up to two prior chemotherapy regimens for metastatic disease, olaparib was compared with physician's-choice chemotherapy. Olaparib produced a higher response rate (59.9% vs 28.8%) and longer median progression-free survival (7.0 vs 4.2 months; HR 0.58), but overall survival did not differ significantly (3-year survival 27.9% vs 21.2% in post-hoc extended follow-up; HR 0.89, 95% CI 0.67-1.18), and grade 3 or higher adverse events were less frequent with olaparib (36.6% vs 50.5%).", "takeaway_ko": "전이성 질환에 대해 항암화학요법을 최대 2차례 받은 생식세포 BRCA 변이 HER2 음성 전이성 유방암 환자 302명을 대상으로, 올라파립과 의사 선택 항암화학요법을 비교하였습니다. 올라파립군은 반응률이 더 높았고(59.9% 대 28.8%) 무진행생존기간 중앙값도 더 길었으나(7.0개월 대 4.2개월; HR 0.58), 전체생존에는 통계적으로 유의한 차이가 없었습니다(사후 연장 추적관찰에서 3년 생존율 27.9% 대 21.2%; HR 0.89, 95% CI 0.67-1.18). 3등급 이상 이상반응은 올라파립군에서 더 적었습니다(36.6% 대 50.5%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-FORT101", "trial": "G-FORT101", "papers": [], "pages": [ { "key": "fortitude101-lba10", "title": "FORTITUDE-101 — ESMO 2025 LBA10 results abstract and table", "url": "https://www.annalsofoncology.org/article/S0923-7534(25)04862-8/fulltext", "file": "data/sources/pages/fortitude101-lba10.txt" } ], "targets": [ "FGFR2" ], "biomarkers": [], "subtypes": [], "limits": "Conference-abstract evidence: a full clinical manuscript and presentation were not reviewed for this record, and the received registry has no posted structured results. Primary interim statistical success and attenuation at descriptive longer follow-up must both be retained; the later confidence interval is not a new formal failure test. The efficacy result applies to the prespecified >=10% staining population, not all enrolled FGFR2b-positive patients. Registry eligibility currently states >=10%, whereas the result abstract describes >0% enrollment; the protocol amendment history has not been reconciled. Safety is analyzed by treatment received. Biomarker prescreening prevalence and an unread erratum to a separate prevalence report are not efficacy evidence. No inference is made about the reason for FORTITUDE-102 termination or effects with chemoimmunotherapy.", "label": "FORTITUDE-101 (ESMO 2025 LBA10)", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Previously untreated, unresectable locally advanced or metastatic HER2-non-positive gastric or gastroesophageal junction adenocarcinoma with centrally confirmed FGFR2b overexpression", "population": "Total enrolled N=547 (FGFR2b >0% 2+/3+); prespecified primary efficacy subset FGFR2b >=10% 2+/3+ TC (N=324: 159 bemarituzumab + mFOLFOX6, 165 placebo + mFOLFOX6); as-treated safety cohort (N=542: 275 bemarituzumab, 267 placebo)", "claim": "The conference abstract reports 547 enrolled patients. In the prespecified efficacy population with FGFR2b 2+/3+ staining in >=10% of tumor cells (159 bemarituzumab; 165 placebo), the primary interim analysis crossed the OS efficacy boundary with full alpha spent: median OS was 17.9 versus 12.5 months (HR 0.61, 95% CI 0.43-0.86; P=0.005). At the subsequent descriptive follow-up, median OS was 14.5 versus 13.2 months (HR 0.82, 95% CI 0.62-1.08). In the as-treated safety population (275 versus 267), grade >=3 treatment-emergent adverse events occurred in 89.5% versus 78.7%, and grade >=3 treatment-related adverse events in 60.0% versus 18.4%. The abstract attributes the higher incidence of severe treatment-emergent events mainly to corneal events.", "program": "gastric", "by": "Gemini Flash3.8", "added": "2026-10-01", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-FORT101", "nct": "NCT05052801", "acronym": "FORTITUDE-101", "title": "Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 547, "sponsor": "Amgen", "sponsorClass": "INDUSTRY", "collaborators": [ "Zai Lab (China only)" ], "hasResults": false, "start": "2022-03-07", "lastUpdate": "2026-10-23", "url": "https://clinicaltrials.gov/study/NCT05052801" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-ASCENT03", "trial": "B-ASCENT03", "papers": [ { "key": "P-ASCENT03", "pmid": "41124233", "title": "Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41124233/", "doi": "10.1056/NEJMoa2511734", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "Evidence unit is based only on the supplied primary abstract and registry record for NCT05382299, with no full-text review. Primary report denominator of 558 patients is retained unchanged; current registry actual enrollment of 623 is explicitly unreconciled and is not claimed as a larger analysis. Overall survival was a secondary endpoint but no overall survival number was reported in the abstract, and no inference about overall survival is made. Grade 3 or higher adverse events are reported as adverse events and are not described as treatment related, and per-arm safety denominators were not reported in the abstract. Design was open label with blinded independent central review for progression-free survival. Two correspondence items linked to the primary report, PMID 41885990 (N Engl J Med. 2026 Feb 5;394(6):620) and PMID 41885991 (N Engl J Med. 2026 Feb 5;394(6):620-621), both with empty supplied abstracts, are retained as metadata only with bodies unread and are not treated as corrections. The registry record is the same study and not an independent study. Immunotherapy ineligibility is not equated with PD-L1 negativity alone.", "label": "ASCENT-03", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Previously untreated locally advanced unresectable or metastatic triple-negative breast cancer in the first-line advanced setting.", "population": "Patients with previously untreated advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions, including both patients with PD-L1-negative tumors with combined positive score less than 10 and patients with PD-L1-positive tumors with combined positive score 10 or higher.", "claim": "This international, open-label, randomized phase 3 trial assigned 558 patients 1:1 to sacituzumab govitecan or chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary endpoint, progression-free survival assessed by blinded independent central review, was significantly longer with sacituzumab govitecan: median 9.7 months (95% CI, 8.1 to 11.1) versus 6.9 months (95% CI, 5.6 to 8.2); the stratified hazard ratio for disease progression or death was 0.62 (95% CI, 0.50 to 0.77; P<0.001). Objective response was confirmed in 48% (95% CI, 42 to 54) versus 46% (95% CI, 40 to 52), with median duration of response 12.2 months (95% CI, 9.7 to 13.8) versus 7.2 months (95% CI, 5.7 to 8.4). Overall survival was listed as a secondary endpoint; the source abstract reported no numeric result for it. Adverse events of grade 3 or higher occurred in 66% with sacituzumab govitecan (most frequently neutropenia in 43%, diarrhea in 9%, and leukopenia in 7%) and in 62% with chemotherapy (most frequently neutropenia in 41%, anemia in 16%, and leukopenia in 13%). Adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug occurred in 4% and 12%, respectively.", "program": "breast", "by": "Muse Spark1.3", "added": "2026-10-01", "reviewedBy": "Gemini Flash3.8", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-ASCENT03", "nct": "NCT05382299", "acronym": "ASCENT-03", "title": "Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 623, "sponsor": "Gilead Sciences", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2022-07-20", "lastUpdate": "2026-04-06", "url": "https://clinicaltrials.gov/study/NCT05382299" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival assessed by blinded independent central review", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 558, "assessment": "blinded independent central review", "quote": "In this international, phase 3, open-label, randomized trial, we enrolled patients with previously untreated, advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions. … were assigned in a 1:1 ratio to receive sacituzumab govitecan or chemotherapy … The primary end point was progression-free survival, assessed by blinded independent central review. … Among 558 patients" }, "effect": { "measure": "HR", "value": 0.62, "ci_low": 0.5, "ci_high": 0.77, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for disease progression or death, 0.62; 95% CI, 0.50 to 0.77; P<0.001)" }, "landmark": [ { "endpoint": "Confirmed objective response", "timepoint": "Best confirmed response (no fixed time point)", "experimental_pct": 48, "control_pct": 46, "higher_is_better": true, "experimental_arm": "Sacituzumab govitecan", "control_arm": "Chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin)", "quote": "An objective response was confirmed in 48% of patients (95% CI, 42 to 54) who received sacituzumab govitecan and 46% (95% CI, 40 to 52) who received chemotherapy", "difference_pp": 2, "nnt": 50, "quote_note": "ASCENT-03, N Engl J Med 2025, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": 66, "grade3plus_control_pct": 62, "discontinuation_experimental_pct": 4, "discontinuation_control_pct": 12, "treatment_related_deaths": null, "quote": "Adverse events of grade 3 or higher occurred in 66% of patients who received sacituzumab govitecan (most frequently neutropenia [in 43%], diarrhea [in 9%], and leukopenia [in 7%]) and in 62% of patients who received chemotherapy (most frequently neutropenia [in 41%], anemia [in 16%], and leukopenia [in 13%]). The incidence of adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug was 4% and 12%, respectively." }, "takeaway_en": "In 558 patients with previously untreated advanced triple-negative breast cancer who could not receive PD-1/PD-L1 inhibitors, sacituzumab govitecan was compared with chemotherapy. Median progression-free survival was 9.7 versus 6.9 months (hazard ratio 0.62). Confirmed response rates were similar at 48% versus 46%, and overall survival results were not reported. Grade 3 or higher adverse events occurred in 66% versus 62%, with neutropenia in 43% and diarrhea in 9% on sacituzumab govitecan, while treatment discontinuation for adverse events was 4% versus 12%.", "takeaway_ko": "PD-1/PD-L1 억제제를 사용할 수 없는 이전 치료력이 없는 진행성 삼중음성 유방암 환자 558명에서 사시투주맙 고비테칸과 항암화학요법을 비교했으며, 무진행 생존기간 중앙값은 9.7개월 대 6.9개월이었습니다(위험비 0.62). 확정 객관적 반응률은 48% 대 46%로 비슷했고, 전체 생존 결과는 보고되지 않았습니다. 3등급 이상 이상반응은 66% 대 62%에서 발생했으며, 사시투주맙 고비테칸군에서 호중구감소증이 43%, 설사가 9%였습니다. 이상반응으로 인한 치료 중단은 4% 대 12%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-TROPIONB02", "trial": "B-TROPIONB02", "papers": [ { "key": "P-TROPIONB02", "pmid": "41937088", "title": "Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41937088/", "doi": "10.1016/j.annonc.2026.03.008", "errata": [] }, { "key": "P-TROPIONB02Protocol", "pmid": "37526149", "title": "TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer.", "journal": "Future Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37526149/", "doi": "10.2217/fon-2023-0228", "errata": [] } ], "pages": [], "targets": [ "TACSTD2" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "Evidence is derived strictly from the primary study abstract (PMID 41937088), the trial protocol publication (PMID 37526149; not an independent study), and clinical trial registry data (NCT05374512); full-text review was not conducted. The trial was open-label. While ITT randomized counts were 323 for datopotamab deruxtecan and 321 for chemotherapy, exact denominators for the treated safety population were not explicitly stated in the primary abstract; exact safety cohort denominators must not be inferred or calculated by dividing TRAE counts (105 and 89) by randomized counts. The reported absence of treatment-related deaths does not imply zero all-cause mortality, which remains unreported in the abstract. Results are restricted to untreated advanced TNBC where immunotherapy is not an option and cannot be generalized as a blanket class effect for all antibody-drug conjugates or as a clinical recommendation across broader TNBC settings.", "label": "TROPION-Breast02", "kind": "rct", "level": "clinical", "result": "positive", "setting": "International, multicenter, open-label, randomized 1:1, phase III trial (TROPION-Breast02; NCT05374512) conducted across sites globally with random assignment between May 16, 2022, and June 11, 2024.", "population": "644 patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy (PD-1/PD-L1 inhibitor therapy) was not an option (including PD-L1-negative disease as well as PD-L1-positive disease with relapse following prior early-stage anti-PD-[L]1 therapy, contraindicating comorbidities, or lack of regulatory access; not restricted to PD-L1-negative status alone), randomized 1:1 to datopotamab deruxtecan (n = 323) or investigator's choice of chemotherapy (n = 321).", "claim": "In the intention-to-treat analysis of the phase III TROPION-Breast02 trial, datopotamab deruxtecan (6 mg/kg IV every 3 weeks) demonstrated statistically significant improvements in both dual primary endpoints compared with investigator's choice of chemotherapy. Median progression-free survival (PFS by BICR per RECIST v1.1) was 10.8 months (95% CI 8.6-13.0) versus 5.6 months (95% CI 5.0-7.0), with a hazard ratio of 0.57 (99% CI 0.44-0.73; P < 0.0001), and median overall survival (OS) was 23.7 months (95% CI 19.8-25.6) versus 18.7 months (95% CI 16.0-21.8), with a hazard ratio of 0.79 (95.01% CI 0.64-0.98; P = 0.029). Grade ≥3 treatment-related adverse events (TRAEs) were reported in 105 (33%) patients in the datopotamab deruxtecan arm and 89 (29%) patients in the chemotherapy arm. TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients, respectively. No treatment-related deaths occurred in either study arm.", "program": "breast", "by": "Gemini Flash3.8", "added": "2026-10-01", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-TROPIONB02", "nct": "NCT05374512", "acronym": null, "title": "A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 644, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo" ], "hasResults": false, "start": "2022-05-16", "lastUpdate": "2026-05-15", "url": "https://clinicaltrials.gov/study/NCT05374512" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Dual primary endpoints: progression-free survival (blinded independent central review per RECIST version 1.1) and overall survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 644, "assessment": "blinded independent central review", "quote": "In the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomly assigned 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator's choice of chemotherapy. … Dual primary endpoints were progression-free survival (PFS; blinded independent central review per RECIST version 1.1) and overall survival (OS). … Between 16 May 2022 and 11 June 2024, 644 patients were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321)." }, "effect": { "measure": "HR", "value": 0.57, "ci_low": 0.44, "ci_high": 0.73, "ci_level": "99%", "p": "P < 0.0001", "endpoint": "PFS (blinded independent central review); 99% CI. Co-primary OS: HR 0.79 (95.01% CI 0.64-0.98); P = 0.029", "quote": "Median PFS was 10.8 months [95% confidence interval (CI) 8.6-13.0] with Dato-DXd and 5.6 months (95% CI 5.0-7.0) with chemotherapy [hazard ratio 0.57 (99% CI 0.44-0.73); P < 0.0001]. Median OS was 23.7 months (95% CI 19.8-25.6) and 18.7 months (95% CI 16.0-21.8) with Dato-DXd and chemotherapy, respectively [hazard ratio 0.79 (95.01% CI 0.64-0.98); P = 0.029]." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 33, "grade3plus_control_pct": 29, "discontinuation_experimental_pct": 4, "discontinuation_control_pct": 7, "treatment_related_deaths": "None in either arm", "quote": "Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm." }, "takeaway_en": "In 644 patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy was not an option, datopotamab deruxtecan was compared with investigator's choice of chemotherapy. It improved progression-free survival (median 10.8 vs 5.6 months; HR 0.57, 99% CI 0.44-0.73) and overall survival (median 23.7 vs 18.7 months; HR 0.79, 95.01% CI 0.64-0.98). Grade ≥3 treatment-related adverse events were slightly more frequent with datopotamab deruxtecan (33% vs 29%), but fewer patients discontinued treatment because of adverse events (4% vs 7%), and there were no treatment-related deaths in either arm.", "takeaway_ko": "면역항암제 치료가 적합하지 않은, 이전 치료 경험이 없는 수술 불가능한 국소재발성 또는 전이성 삼중음성 유방암 환자 644명을 대상으로 다토포타맙 데룩스테칸과 연구자 선택 항암화학요법을 비교하였습니다. 다토포타맙 데룩스테칸은 무진행생존기간(중앙값 10.8개월 대 5.6개월; 위험비 0.57, 99% 신뢰구간 0.44-0.73)과 전체생존기간(중앙값 23.7개월 대 18.7개월; 위험비 0.79, 95.01% 신뢰구간 0.64-0.98)을 모두 개선하였습니다. 3등급 이상 치료 관련 이상반응은 다토포타맙 데룩스테칸군에서 약간 더 많았으나(33% 대 29%), 이상반응으로 인한 치료 중단은 더 적었고(4% 대 7%), 두 군 모두 치료 관련 사망은 없었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DRAGONIV", "trial": "G-DRAGONIV", "papers": [ { "key": "P-DRAGONIV", "pmid": "39383487", "title": "Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05).", "journal": "J Clin Oncol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39383487/", "doi": "10.1200/JCO.24.00795", "errata": [] } ], "pages": [], "targets": [ "PDCD1", "KDR" ], "biomarkers": [], "subtypes": [], "limits": "Primary abstract only; full text not reviewed. This pCR report covers the first 360 randomized SOXRC/SOX patients with an opportunity for surgery, while the current registry lists planned enrollment of 580 across the trial; these are different scopes and do not establish a larger efficacy analysis. Co-primary EFS is not reported here, so pCR benefit alone does not establish recurrence or survival benefit. Individual camrelizumab and rivoceranib contributions are not isolated. The reported 13.7 percentage-point contrast is retained without inferring its adjustment method. The linked editorial is not an erratum; its full text was not reviewed.", "label": "DRAGON IV/CAP 05 · perioperative pathologic response", "kind": "rct", "level": "clinical", "result": "positive", "setting": "perioperative locally advanced gastric/gastroesophageal junction adenocarcinoma", "population": "T3-4aN+M0 gastric/GEJ adenocarcinoma randomly assigned to SOXRC or SOX", "claim": "In the phase III DRAGON IV/CAP 05 trial, perioperative SOXRC (camrelizumab plus low-dose rivoceranib and SOX) significantly increased pathologic complete response (pCR) versus SOX alone in locally advanced T3-4aN+M0 gastric/GEJ adenocarcinoma. Among the first 360 randomized patients who had the opportunity to undergo surgery (180 per group), pCR was 18.3% (95% CI, 13.0 to 24.8) for SOXRC versus 5.0% (95% CI, 2.3 to 9.3) for SOX (source-reported difference 13.7 percentage points, 95% CI, 7.2 to 20.1; OR 4.5, 95% CI, 2.1 to 9.9; one-sided P < .0001, crossing the prespecified boundary of P = .005). Neoadjuvant therapy was received by 99% versus 98% of patients and completed by 91% versus 94%, and surgery was performed in 86% versus 87%. Surgical complications occurred in 27% versus 33%; grade ≥3 neoadjuvant treatment-related adverse events occurred in 34% versus 17%. Event-free survival (EFS), a co-primary endpoint, is not reported in this abstract. A third arm (SOXR) was closed early on IDMC recommendation, based on safety data from the first 103 patients across the three arms.", "program": "gastric", "by": "Muse Spark1.3", "added": "2026-10-01", "reviewedBy": "Gemini Flash3.8", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-DRAGONIV", "nct": "NCT04208347", "acronym": null, "title": "Perioperative Treatment of Combined SOX With Apatinib and Camrelizumab for Oesophagogastric Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 580, "sponsor": "Ruijin Hospital", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2019-12-18", "lastUpdate": "2026-01-23", "url": "https://clinicaltrials.gov/study/NCT04208347" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathologic complete response (pCR) and event-free survival (co-primary); this report presents pCR only", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) … This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups." }, "effect": { "measure": "OR", "value": 4.5, "ci_low": 2.1, "ci_high": 9.9, "ci_level": "95%", "p": "one-sided P <.0001 (prespecified threshold P = .005)", "endpoint": "pCR", "quote": "The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005." }, "landmark": [ { "endpoint": "pCR", "timepoint": "after neoadjuvant therapy and surgery", "experimental_pct": 18.3, "control_pct": 5, "higher_is_better": true, "experimental_arm": "SOXRC (camrelizumab + low-dose rivoceranib + SOX)", "control_arm": "SOX", "quote": "The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group", "difference_pp": 13.3, "nnt": 8, "quote_note": "P-DRAGONIV (J Clin Oncol 2025, only report" } ], "harms": { "grade3plus_experimental_pct": 34, "grade3plus_control_pct": 17, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively." }, "takeaway_en": "In patients with T3-4aN+M0 gastric or gastroesophageal junction adenocarcinoma, perioperative camrelizumab plus low-dose rivoceranib and SOX (SOXRC) raised the pathologic complete response rate from 5.0% with SOX alone to 18.3%, an absolute difference of 13.7%; event-free survival, the co-primary endpoint, is not yet reported. Grade ≥3 neoadjuvant treatment-related adverse events were more frequent with SOXRC (34% vs 17%), while surgical complications were 27% vs 33%.", "takeaway_ko": "T3-4aN+M0 국소진행성 위 또는 위식도접합부 선암 환자에서, 수술 전후 캄렐리주맙과 저용량 리보세라닙을 SOX에 추가한 SOXRC 요법은 병리학적 완전관해율을 SOX 단독의 5.0%에서 18.3%로 높였습니다(절대 차이 13.7%). 공동 일차 평가변수인 무사건생존은 아직 보고되지 않았습니다. 3등급 이상의 수술 전 치료 관련 이상반응은 SOXRC군에서 더 많았고(34% 대 17%), 수술 합병증은 27% 대 33%였습니다.", "certainty": { "level": "moderate", "reasons": [ "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-NEONIPIGA", "trial": "G-NEONIPIGA", "papers": [ { "key": "P-NEONIPIGA", "pmid": "35969830", "title": "Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/35969830/", "doi": "10.1200/JCO.22.00686", "errata": [] }, { "key": "P-NEONIPIGAProtocol", "pmid": "32057467", "title": "[Localized MSI/dMMR gastric cancer patients, perioperative immunotherapy instead of chemotherapy: The GERCOR NEONIPIGA phase II study is opened to recruitment].", "journal": "Bull Cancer", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32057467/", "doi": "10.1016/j.bulcan.2019.11.016", "errata": [] }, { "key": "P-NEONIPIGALong26", "pmid": "42879140", "title": "Nivolumab-Ipilimumab for Localized Microsatellite Instability-High Gastric/Gastroesophageal Junction Adenocarcinoma: The Phase 2 NEONIPIGA Nonrandomized Clinical Trial.", "journal": "JAMA Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42879140/", "doi": "10.1001/jamaoncol.2026.4162", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI" ], "subtypes": [ "G-MSI" ], "limits": "The initial and long-term publications are abstracts only in this review; full methods, protocol amendments and supplements have not been audited. This uncontrolled single-arm study cannot identify a comparative survival benefit over surgery or chemotherapy. Initial pCR uses the operated population, long-term overall survival uses the intention-to-treat population, and long-term event-free survival excludes the protocol-ineligible metastatic participant. These denominators and endpoints must not be pooled. Selected complete responses among patients who did not undergo surgery cannot establish the safety of routine surgery omission. Long-term follow-up adds observed survival, not proof of cure or equivalence to surgery; confidence intervals are wide, and the absence of a concurrent control prevents a superiority or noninferiority conclusion. Deaths and incomplete treatment remain part of the evidence; no additional late toxicity reported in the abstract does not erase early toxicity or postoperative harm. The current registry remains on an older update, with estimated enrollment and disease-free survival wording, while the later article reports event-free survival; endpoint definitions and amendments require original-source reconciliation before direct comparison. No new trial, independent cohort, patient access, own execution or prospective prediction is counted.", "label": "NEONIPIGA · single-arm perioperative immunotherapy", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "neoadjuvant nivolumab plus ipilimumab followed by surgery and adjuvant nivolumab in resectable dMMR/MSI-H gastric or GEJ adenocarcinoma", "population": "locally advanced resectable dMMR/MSI-H cT2-T4NxM0 gastric/GEJ adenocarcinoma (32 enrolled, including 1 wrongly included cT3N1M1)", "claim": "In the single-arm phase II GERCOR NEONIPIGA study, 32 patients with locally advanced resectable dMMR/MSI-H gastric/GEJ adenocarcinoma received neoadjuvant nivolumab plus ipilimumab (27 completed all planned cycles). Twenty-nine patients underwent surgery; all 29 achieved R0 resection, and 17 achieved pathologic complete response (pCR, pT0N0: 17/29 [58.6%]; 90% CI, 41.8 to 74.1). Three patients did not undergo surgery (two refused, one had baseline metastasis) and had complete endoscopic responses with tumor-free biopsies and normal CT scans. Twenty-three operated patients received adjuvant nivolumab. Grade 3/4 neoadjuvant treatment-related adverse events occurred in 6 patients (19%). Postoperative surgical morbidity was 55%, including one postoperative death. At a median follow-up of 14.9 months (95% CI, 10.6 to 17.6), no disease relapse was documented and one patient died without relapse. These findings describe activity in a single arm and provide no comparative efficacy evidence. The later long-term report describes a median follow-up of 48.3 months. Four-year overall survival was 84.1% (95% CI, 65.8%-93.0%) in the 32-patient intention-to-treat population; four-year event-free survival was 83.5% (95% CI, 64.8%-92.8%) in the 31 surgery-eligible patients. One patient relapsed with cerebral metastases. Six deaths were reported, including deaths related to gastric cancer or treatment and unrelated deaths. Only 14 patients (44%) received all treatment as planned. The authors found no clear evidence of improved survival relative to outcomes in other studies of surgery alone; this is not a randomized comparison.", "program": "gastric", "by": "Muse Spark1.3", "added": "2026-10-01", "reviewedBy": "Gemini Flash3.8", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "G-NEONIPIGA", "nct": "NCT04006262", "acronym": "NEONIPIGA", "title": "Pre-operative Nivolumab and Ipilimumab, Followed by Post-operative Nivolumab, for MSI/dMMR Oeso-gastric Adenocarcinoma.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 32, "sponsor": "GERCOR - Multidisciplinary Oncology Cooperative Group", "sponsorClass": "OTHER", "collaborators": [ "Bristol-Myers Squibb" ], "hasResults": false, "start": "2019-10-23", "lastUpdate": "2025-06-15", "url": "https://clinicaltrials.gov/study/NCT04006262" }, "sources": 4, "corrections": 0, "analysisRecord": null }, { "id": "U-DB11", "trial": "B-DB11", "papers": [ { "key": "P-DB11", "pmid": "41130363", "title": "Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41130363/", "doi": "10.1016/j.annonc.2025.10.019", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Evidence is abstract only without full-text review. pCR benefit alone does not establish survival benefit. EFS is highly immature with confidence interval crossing 1 and does not establish benefit. Safety percentages use safety analysis set; denominators were not reported and were not inferred from ITT. Early T-DXd-alone closure is reported only as following IDMC recommendation with no reason stated. No treatment guidance is given.", "label": "DESTINY-Breast11 · neoadjuvant HER2 regimen comparison", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Neoadjuvant, multicenter, open-label phase 3 randomized trial", "population": "High-risk (≥cT3cN0 or cT0-4cN1-3) HER2-positive early breast cancer; randomized females: 286 T-DXd, 321 T-DXd-THP, 320 ddAC-THP", "claim": "In the open-label phase 3 DESTINY-Breast11 trial, female patients with high-risk HER2-positive early breast cancer were randomized to T-DXd (n=286), T-DXd-THP (n=321), or ddAC-THP (n=320). Enrollment in the T-DXd-alone arm closed early on the recommendation of the IDMC; the abstract gives no reason. pCR (ypT0/is ypN0, ITT) was 43.0% (n=123) with T-DXd, 67.3% (n=216) with T-DXd-THP, and 56.3% (n=180) with ddAC-THP. The reported difference between T-DXd-THP and ddAC-THP was 11.2 percentage points (95% CI 4.0 to 18.3; P=0.003). EFS HR was 0.56 (95% CI 0.26 to 1.17) at 4.5% maturity. Grade ≥3 adverse events occurred in 22.6% (n=64), 37.5% (n=120), and 55.8% (n=174); serious events in 10.2% (n=29), 10.6% (n=34), and 20.2% (n=63); and left-ventricular dysfunction in 0.7% (n=2), 1.3% (n=4), and 6.1% (n=19). Drug-related ILD/pneumonitis occurred in 4.9% (n=14), 4.4% (n=14), and 5.1% (n=16). Treatment-related deaths occurred in 0.3% (n=1, T-DXd-THP) and 0.6% (n=2, ddAC-THP).", "program": "breast", "by": "Gemini Flash3.8", "added": "2026-10-01", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-DB11", "nct": "NCT05113251", "acronym": null, "title": "Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 927, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo" ], "hasResults": true, "start": "2021-10-25", "lastUpdate": "2026-08-11", "url": "https://clinicaltrials.gov/study/NCT05113251" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population)", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": null, "assessment": "not stated", "quote": "This open-label, phase III trial (147 sites, 18 countries) randomised adults 1 : 1 : 1 to T-DXd (×8 cycles), T-DXd-THP (4 + 4 cycles), or ddAC-THP (4 + 4 cycles). T-DXd-alone arm enrolment closed early following the Independent Data Monitoring Committee recommendation. … 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised." }, "effect": { "measure": "difference", "value": 11.2, "ci_low": 4, "ci_high": 18.3, "ci_level": "95%", "p": "0.003", "endpoint": "pCR (T-DXd-THP versus ddAC-THP, absolute rate difference)", "quote": "T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11.2% [95% confidence interval (CI), 4.0% to 18.3%, P = 0.003]" }, "landmark": [ { "endpoint": "pCR (ypT0/is ypN0), ITT", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 67.3, "control_pct": 56.3, "higher_is_better": true, "experimental_arm": "T-DXd-THP", "control_arm": "ddAC-THP", "quote": "pCR rates were 43.0% (T-DXd, n = 123), 67.3% (T-DXd-THP, n = 216), and 56.3% (ddAC-THP, n = 180).", "difference_pp": 11, "nnt": 10, "quote_note": "single paper, P-DB11" }, { "endpoint": "pCR, hormone receptor-positive subgroup", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 61.4, "control_pct": 52.3, "higher_is_better": true, "experimental_arm": "T-DXd-THP", "control_arm": "ddAC-THP", "quote": "hormone receptor (HR)-positive [61.4% (n/N = 145/236) versus 52.3% (n/N = 123/235); difference in pCR (ΔpCR) 9.1% (95% CI 0.2% to 17.9%)]", "difference_pp": 9.1, "nnt": 11 }, { "endpoint": "pCR, hormone receptor-negative subgroup", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 83.1, "control_pct": 67.1, "higher_is_better": true, "experimental_arm": "T-DXd-THP", "control_arm": "ddAC-THP", "quote": "HR-negative [83.1% (n/N = 69/83) versus 67.1% (n/N = 57/85); ΔpCR 16.1% (95% CI 3.0% to 28.8%)]", "difference_pp": 16, "nnt": 7 }, { "endpoint": "pCR (ypT0/is ypN0), ITT; T-DXd-alone arm (enrolment closed early)", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 43, "control_pct": 56.3, "higher_is_better": true, "experimental_arm": "T-DXd alone", "control_arm": "ddAC-THP", "quote": "pCR rates were 43.0% (T-DXd, n = 123), 67.3% (T-DXd-THP, n = 216), and 56.3% (ddAC-THP, n = 180).", "difference_pp": -13.3, "nnt": null, "nnt_label": "favours control", "nnh": 8 } ], "harms": { "grade3plus_experimental_pct": 37.5, "grade3plus_control_pct": 55.8, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Three treatment-related deaths: T-DXd-THP 0.3% (n = 1); ddAC-THP 0.6% (n = 2)", "quote": "Grade ≥3 adverse events (AE; T-DXd, 22.6% (n = 64); T-DXd-THP, 37.5% (n = 120); ddAC-THP, 55.8% (n = 174)], serious AE [T-DXd, 10.2% (n = 29); T-DXd-THP, 10.6% (n = 34); ddAC-THP, 20.2% (n = 63)], and all-grade left-ventricular dysfunction [T-DXd, 0.7% (n = 2); T-DXd-THP, 1.3% (n = 4); ddAC-THP, 6.1% (n = 19)] rates were lower for T-DXd and T-DXd-THP than ddAC-THP. All-grade adjudicated drug-related interstitial lung disease/pneumonitis rates were low and similar across arms [T-DXd, 4.9% (n = 14); T-DXd-THP, 4.4% (n = 14); ddAC-THP, 5.1% (n = 16)]. Three treatment-related deaths occurred [T-DXd-THP, 0.3% (n = 1); ddAC-THP, 0.6% (n = 2)]." }, "takeaway_en": "In women with high-risk HER2-positive early breast cancer, this open-label phase III trial compared neoadjuvant T-DXd followed by THP with ddAC followed by THP. The T-DXd-THP arm had a pCR of 67.3% versus 56.3% (absolute difference 11.2%, 95% CI 4.0% to 18.3%), while event-free survival data were immature at 4.5% maturity (HR 0.56, 95% CI 0.26 to 1.17); a T-DXd-alone arm (pCR 43.0%) closed early on IDMC recommendation. Grade ≥3 adverse events (37.5% vs 55.8%) and left-ventricular dysfunction (1.3% vs 6.1%) were less frequent with T-DXd-THP, and drug-related interstitial lung disease/pneumonitis was similar (4.4% vs 5.1%).", "takeaway_ko": "고위험 HER2 양성 조기 유방암 여성을 대상으로 한 공개 3상 시험에서 수술 전 T-DXd 후 THP와 ddAC 후 THP를 비교했습니다. T-DXd-THP군의 병리학적 완전관해율은 67.3%로 ddAC-THP군의 56.3%보다 높았습니다(절대 차이 11.2%, 95% CI 4.0–18.3%). 무사건생존 자료는 성숙도 4.5%로 아직 미성숙합니다(HR 0.56, 95% CI 0.26–1.17). T-DXd 단독군(완전관해율 43.0%)은 독립적 자료모니터링위원회 권고로 조기에 등록이 종료되었습니다. 3등급 이상 이상반응(37.5% 대 55.8%)과 좌심실 기능부전(1.3% 대 6.1%)은 T-DXd-THP군에서 적었고, 약물 관련 간질성 폐질환/폐렴은 비슷했습니다(4.4% 대 5.1%).", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-NeoPACT", "trial": "B-NeoPACT", "papers": [ { "key": "P-NeoPACT", "pmid": "37991778", "title": "Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial.", "journal": "JAMA Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37991778/", "doi": "10.1001/jamaoncol.2023.5033", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "Evidence is abstract only without full-text review. Single-arm results are descriptive and do not establish comparative efficacy or de-escalation equivalence. EFS by pCR status is an observational post-treatment association, not causal treatment effect. Biomarker associations do not prove predictive treatment effect. The abstract reports grade 3 or higher immune-mediated events, not the overall severe-toxicity rate. Registry records 120 actual enrollment versus 115 eligible in abstract; discrepancy is explicitly unresolved. No treatment guidance is given.", "label": "NeoPACT · single-arm anthracycline-free chemoimmunotherapy", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "Neoadjuvant, two-center, open-label single-arm phase 2 trial", "population": "115 eligible females with stage I-III triple-negative breast cancer; median age 50 years, 39% node-positive", "claim": "In the single-arm phase 2 NeoPACT trial, 115 eligible female patients with stage I-III triple-negative breast cancer received neoadjuvant carboplatin-docetaxel plus pembrolizumab for 6 cycles. pCR (no invasive tumor in breast and axilla) was 58% (95% CI 48% to 67%); residual cancer burden 0+1 rate was 69% (95% CI 60% to 78%). Estimated 3-year EFS was 86% overall, 98% in those with pCR and 68% in those without pCR. Grade 3 or higher immune-mediated adverse events occurred in 3.5%. In multivariable analyses, sTILs, PD-L1, DDIR, and TIM were each associated with pCR, with areas under curve 0.719, 0.740, 0.699, and 0.715, respectively.", "program": "breast", "by": "Gemini Flash3.8", "added": "2026-10-01", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "trialRecord": { "key": "B-NeoPACT", "nct": "NCT03639948", "acronym": "NeoPACT", "title": "Neoadjuvant Phase II Study of Pembrolizumab And Carboplatin Plus Docetaxel in Triple Negative Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE2" ], "enrollment": 120, "sponsor": "University of Kansas Medical Center", "sponsorClass": "OTHER", "collaborators": [ "Merck Sharp & Dohme LLC" ], "hasResults": true, "start": "2018-09-04", "lastUpdate": "2024-04-11", "url": "https://clinicaltrials.gov/study/NCT03639948" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-ADCLow", "trial": null, "papers": [ { "key": "P-ADCLow", "pmid": "38918555", "title": "Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.", "journal": "Br J Cancer", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38918555/", "doi": "10.1038/s41416-024-02766-9", "errata": [] } ], "pages": [], "targets": [ "ERBB2", "TACSTD2" ], "biomarkers": [ "BM-HER2LOW-B" ], "subtypes": [], "limits": "Selected retrospective cohort requiring both ADCs; nonrandom order, HR imbalance and prior treatment can confound comparisons despite reported multivariable Cox analyses. Methods defines PFS2 from second-ADC initiation to documented progression or death, and OS from second-ADC initiation to death. It states that patients alive and progression-free at cut-off were excluded; the actual handling requires clarification and is not silently interpreted as censoring. Resistance labels are based on clinical response patterns, not demonstrated molecular mechanisms. No causal optimal sequence or survival benefit is established; no detected intervening-chemotherapy association does not prove equivalence. Methods reviewed; quantitative safety results and supplements remain unreviewed.", "label": "ADC-Low · retrospective sequential ADC use", "program": "breast", "kind": "observational", "setting": "multicentre retrospective sequential use", "population": "HER2-low metastatic breast cancer receiving both SG and T-DXd", "level": "clinical", "result": "descriptive", "claim": "In the ADC-Low multicentre retrospective observational study of patients with HER2-low metastatic breast cancer selected for having received both Sacituzumab Govitecan and Trastuzumab Deruxtecan sequentially, with or without intermediary chemotherapy, median progression-free survival 2 was 2.7 months (95% CI: 2.4-3.3) overall, 3.1 months (95% CI: 2.6-3.6) when T-DXd was second and 2.2 months (95% CI: 1.9-2.7) when SG was second. Order was nonrandom: 100/108 HR-negative tumours received SG first and 56/71 HR-positive tumours received T-DXd first. Intermediary chemotherapy had no detected impact. Authors reported primary resistance to the second ADC in 54.4%, while certain patients showed initial response to the second ADC.", "implication": "Descriptive evidence about second-ADC outcomes; does not establish a preferred order.", "by": "Muse Spark1.3", "added": "2026-10-01", "reviewedBy": "Gemini Flash3.8", "sourceCheckedBy": "Codex (GPT-6)", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex integration", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ADCSequence84", "trial": null, "papers": [ { "key": "P-ADCSequence84", "pmid": "40234477", "title": "Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC).", "journal": "NPJ Breast Cancer", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40234477/", "doi": "10.1038/s41523-025-00748-5", "errata": [] } ], "pages": [], "targets": [ "ERBB2", "TACSTD2" ], "biomarkers": [ "BM-HER2LOW-B" ], "subtypes": [], "limits": "Selection for receiving both ADCs, nonrandom order and treatment history can confound comparisons. Methods defines TTF from ADC initiation to discontinuation for any reason, including progression, toxicity or death; TTF is not interchangeable with progression-free survival. Real-world response used physician-directed scans without RECIST reads; rwOS ran from each ADC initiation to death or last known clinical follow-up. Reported multivariable Cox analyses of survival from first-ADC initiation do not establish adequate confounding control. No causal sequence superiority, survival benefit, molecular cross-resistance or equivalence across subgroups is established. Methods reviewed; quantitative safety results and supplements remain unreviewed.", "label": "Sequential ADC cohort · 84 patients", "program": "breast", "kind": "observational", "setting": "Multicenter (5 institutions, 2020-2024)", "population": "84 patients with HER2-low metastatic breast cancer treated sequentially with T-DXd and SG in either order", "level": "clinical", "result": "descriptive", "claim": "In a retrospective cohort of 84 patients with HER2-low metastatic breast cancer receiving both trastuzumab deruxtecan and sacituzumab govitecan at 5 institutions during 2020–2024, median time to treatment failure (TTF) was longer for the first than second ADC across reported HR-status, sequence-order, age, visceral-disease and intervening-therapy groups. Younger age, longer interval from metastatic diagnosis to first ADC and SG as first ADC were associated with longer real-world overall survival from first-ADC initiation. Numerical TTF and survival estimates were not supplied in the abstract.", "implication": "Exploratory descriptive real-world record of sequential ADC exposure in HER2-low MBC, useful as evidence-gap context without establishing an optimal sequence.", "by": "Gemini Flash3.8", "added": "2026-10-01", "reviewedBy": "Muse Spark1.3", "sourceCheckedBy": "Codex (GPT-6)", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3 / Gemini Flash3.8; Codex integration", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-evERA", "trial": "B-evERA", "papers": [ { "key": "P-evERA26", "pmid": "42814929", "title": "Giredestrant plus Everolimus in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42814929/", "doi": "10.1056/NEJMoa2602457", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1", "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Open-label, investigator-assessed PFS. The shared everolimus backbone prevents inference about giredestrant alone or its rank against other ER degraders. The overall population contains the mutation subgroup, not an independent replication; subgroup contrast alone is not a treatment-interaction test. The abstract does not report OS results or a graded-toxicity breakdown; similar overall adverse-event rates do not establish equal safety. Registry selection excludes prior oral SERDs, everolimus and metastatic chemotherapy. Review covers the saved abstract and registry; publisher full text was inaccessible.", "label": "evERA Breast Cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After progression or recurrence on endocrine therapy plus CDK4/6 inhibition", "population": "ER-positive, HER2-negative locally advanced or metastatic breast cancer; ESR1 mutation was not required for all participants", "claim": "Among 373 randomized participants, investigator-assessed PFS was tested first in 207 with ESR1-mutated tumors and then overall. Giredestrant plus everolimus versus standard endocrine therapy plus everolimus yielded median PFS of 10.0 versus 5.5 months in the mutation subgroup (HR 0.38, 95% CI 0.27–0.54), and 8.8 versus 5.5 months overall (HR 0.56, 95% CI 0.44–0.71); both P<0.001. Adverse events occurred in 98.9% versus 96.8%; stomatitis was reported in 47.3% versus 48.9%.", "by": "Codex (GPT-6)", "added": "2026-10-02", "trialRecord": { "key": "B-evERA", "nct": "NCT05306340", "acronym": null, "title": "A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 373, "sponsor": "Genentech, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2022-08-03", "lastUpdate": "2026-06-17", "url": "https://clinicaltrials.gov/study/NCT05306340" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 373, "assessment": "investigator", "quote": "In this phase 3, open-label, randomized trial … The primary end point was investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population. … Overall, 373 patients underwent randomization, with 183 assigned to the giredestrant-everolimus group and 190 to the standard therapy-everolimus group." }, "effect": { "measure": "HR", "value": 0.38, "ci_low": 0.27, "ci_high": 0.54, "ci_level": "95%", "p": "P<0.001", "endpoint": "Investigator-assessed progression-free survival in patients with ESR1-mutated tumors (first hierarchical test of primary end point; overall population HR 0.56, 95% CI 0.44 to 0.71, P<0.001)", "quote": "Among 207 patients with ESR1-mutated tumors, the median progression-free survival was 10.0 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio for disease progression or death, 0.38; 95% confidence interval [CI], 0.27 to 0.54; P<0.001). In the overall population, the median progression-free survival was 8.8 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio, 0.56; 95% CI, 0.44 to 0.71; P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Adverse events occurred in 98.9% of patients who received giredestrant-everolimus and in 96.8% of those who received standard therapy-everolimus. The most common adverse events were stomatitis (in 47.3% of giredestrant-everolimus recipients and 48.9% of standard therapy-everolimus recipients), diarrhea (in 26.9% and 22.6%, respectively), and anemia (in 23.6% and 21.0%)." }, "takeaway_en": "In 373 patients with ER-positive, HER2-negative advanced breast cancer that progressed after a CDK4/6 inhibitor plus endocrine therapy, all-oral giredestrant plus everolimus was compared with standard endocrine therapy plus everolimus in an open-label trial. Investigator-assessed median progression-free survival was 10.0 vs 5.5 months in ESR1-mutated tumors (HR 0.38) and 8.8 vs 5.5 months overall (HR 0.56). Adverse events were similar (98.9% vs 96.8%; stomatitis 47.3% vs 48.9%), and grade 3 or higher event rates were not reported in the abstract.", "takeaway_ko": "CDK4/6 억제제와 내분비요법 후 진행한 ER 양성, HER2 음성 진행성 유방암 환자 373명을 대상으로 한 공개 라벨 시험입니다. 이 시험에서는 경구 지레데스트란트+에베로리무스와 표준 내분비요법+에베로리무스를 비교했으며, 연구자 평가 무진행생존기간 중앙값은 ESR1 변이 종양에서 10.0개월 대 5.5개월(위험비 0.38), 전체 환자에서 8.8개월 대 5.5개월(위험비 0.56)이었습니다. 이상반응 발생률은 98.9% 대 96.8%로 비슷했고 구내염은 47.3% 대 48.9%였으며, 3등급 이상 이상반응 비율은 초록에 보고되지 않았습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-GastricAdjuvantIC26", "trial": null, "papers": [ { "key": "P-GastricAdjuvantIC26", "pmid": "42815617", "title": "Association of adjuvant immunotherapy with survival outcomes among patients with locally advanced gastric cancer after neoadjuvant immunochemotherapy: a propensity score-matched cohort study.", "journal": "J Gastrointest Surg", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42815617/", "doi": "10.1016/j.gassur.2026.102618", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Nonrandomized propensity matching cannot remove unmeasured selection or time-related bias. Nonsignificant survival differences do not establish equivalence, noninferiority or the safety of treatment omission. Reported immune-related-event proportions do not establish graded severity or component-specific causation. Full text was inaccessible, so matching variables, time origin, postoperative selection and regimens remain unverified. The authors propose possible omission pending randomized validation; this library does not adopt an omission recommendation or extend it to every pathological stage.", "label": "Post-NAIC adjuvant immunotherapy · matched gastric cohort", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Postoperative immunochemotherapy versus chemotherapy after neoadjuvant immunochemotherapy", "population": "Patients with locally advanced gastric cancer who received preoperative immunochemotherapy and surgery; matched observational comparison", "claim": "The report included 233 patients before matching and 188 after matching, 94 per group. For chemotherapy alone versus immunochemotherapy, reported 3-year DFS was 77.6% versus 75.5% (P=.534) and OS 88.2% versus 86.1% (P=.593). Immune-related adverse events were reported in 27.66% versus 43.62% (P=.021).", "by": "Codex (GPT-6)", "added": "2026-10-02", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-NEO", "trial": "C-NEO", "papers": [ { "key": "P-NEO", "pmid": "35981270", "title": "Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/35981270/", "doi": "10.1200/JCO.22.00184", "errata": [] }, { "key": "P-NEOctDNA", "pmid": "42826364", "title": "Tumor-Free Circulating Tumor DNA in Node-Negative Rectal Cancers Undergoing Neoadjuvant Chemotherapy, Excision, and Observation in the Phase II NEO Trial (CO.28).", "journal": "JCO Precis Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42826364/", "doi": "10.1200/PO-26-00459", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This is an exploratory assay analysis within a single-arm trial, not a randomized ctDNA-guided management strategy. Recommendation for TME is not proof of residual cancer in every recommended patient, nor evidence that all underwent TME. Non-detection did not remove the recommendation for surgery. Missing longitudinal samples prevent generalizing detection performance to all recurrences. The ctDNA full text was inaccessible; assay thresholds, missingness and timing need review. Tissue-free describes an assay not requiring tumor tissue, not absence of cancer. The primary and ctDNA papers count as one trial.", "label": "NEO / CO.28 — organ preservation and ctDNA", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "Neoadjuvant chemotherapy followed by transanal excision; exploratory residual-disease assay analysis", "population": "Node-negative early rectal cancer in the single-arm NEO trial; ctDNA subset with available plasma", "claim": "At least one ctDNA sample was available from 91.4% of the 58 trial participants. After chemotherapy and before local excision, TME was recommended for 4 of 4 patients with detectable ctDNA and for 16 of 42 with undetectable ctDNA. There were five recurrences, but longitudinal plasma samples were available for only two of the recurrent cases, both local; one of these had detectable ctDNA at progression.", "by": "Codex (GPT-6)", "added": "2026-10-03", "trialRecord": { "key": "C-NEO", "nct": "NCT03259035", "acronym": null, "title": "NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 58, "sponsor": "Canadian Cancer Trials Group", "sponsorClass": "NETWORK", "collaborators": [], "hasResults": true, "start": "2018-06-29", "lastUpdate": "2026-04-09", "url": "https://clinicaltrials.gov/study/NCT03259035" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-FAHCDK9", "trial": null, "papers": [ { "key": "P-FAHCDK9", "pmid": "42814811", "title": "A noncanonical function of the tyrosine degradation enzyme FAH drives CDK4/6 inhibitor resistance in breast cancer.", "journal": "Sci Adv", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42814811/", "doi": "10.1126/sciadv.aef1145", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "Tumor associations and model perturbations do not establish a clinically validated predictive biomarker or patient benefit. Full text places the combination experiment in FAH-overexpressing patient-derived organoids and calls for further models and in vivo efficacy and safety assessment. AlphaFold multimer was used to propose an interaction site before mutation and functional tests; predicted structure alone did not validate the mechanism. FAH and CDK9 lack approved atlas entries and are not relabeled as an existing target.", "label": "Nuclear FAH–CDK9 resistance mechanism", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Mechanistic study of resistance to CDK4/6 inhibition", "population": "HR-positive breast cancer patient-derived models and archived tumor specimens", "claim": "The study linked movement of FAH into the nucleus during CDK4/6 inhibition with a CDK9 interaction and resistance in breast cancer models. Nuclear FAH was enriched in relapsed patient tumors, and CDK9 inhibition reversed FAH-mediated resistance in the tested models.", "by": "Codex (GPT-6)", "added": "2026-10-03", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-P53CRLM26", "trial": null, "papers": [ { "key": "P-P53CRLM26", "pmid": "42827381", "title": "Pattern-Based P53 Immunohistochemistry Predicts Recurrence in Colorectal Liver Metastases Without Complete Pathologic Response After Neoadjuvant Chemotherapy.", "journal": "Cancer Rep (Hoboken)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42827381/", "doi": "10.1002/cnr2.70701", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This small selected cohort estimates a prognostic association, not benefit from p53-guided treatment. Post-treatment staining is not a pretreatment selection test or direct TP53 genotyping. Events, adjustment specification and external validation remain unverified because full text was inaccessible. The indexed abstract contains an apparent production-text artifact; no numerical correction is inferred.", "program": "colorectal", "result": "descriptive", "by": "Codex (GPT-6)", "added": "2026-10-04", "label": "Post-treatment p53 IHC and recurrence after liver metastasectomy", "kind": "observational", "level": "clinical", "setting": "Resected colorectal liver metastases after neoadjuvant FOLFOXIRI", "population": "Selected patients without pathological complete response", "claim": "In a prospective cohort of 39 patients, aberrant p53 staining was observed in 20 (51.3%). The reported multivariable association with shorter recurrence-free survival was HR 3.78 (95% CI 1.56–9.15; P=0.003).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-TFAMTBK1", "trial": null, "papers": [ { "key": "P-TFAMTBK1", "pmid": "42827098", "title": "TFAM loss drives oxaliplatin resistance by linking mtDNA release to STING-TBK1-mediated lysophagy.", "journal": "Oncogene", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42827098/", "doi": "10.1038/s41388-026-03990-8", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Model effects do not establish patient benefit or a validated selection biomarker. Full methods were behind subscription access; inhibitor specificity, exposure, model numbers and immune context remain unreviewed. TFAM and TBK1 lack approved atlas entries. No new simulation or independent replication was performed.", "program": "colorectal", "result": "descriptive", "by": "Codex (GPT-6)", "added": "2026-10-04", "label": "TFAM–STING–TBK1 lysophagy in oxaliplatin resistance", "kind": "preclinical", "level": "preclinical", "setting": "Mechanistic study of acquired oxaliplatin resistance", "population": "Colorectal cancer cells, xenografts and patient-derived organoids", "claim": "The study linked TFAM loss and cytosolic mitochondrial DNA release to STING–TBK1-dependent clearance of damaged lysosomes. TBK1 inhibition restored oxaliplatin sensitivity and reduced tumor growth in the tested xenograft and organoid models.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ILCLuminal26", "trial": null, "papers": [ { "key": "P-ILCLuminal26", "pmid": "42828641", "title": "Long-term outcomes of invasive lobular carcinoma compared with invasive ductal carcinoma in HR-positive/HER2-negative breast cancer: a focus on luminal subtypes.", "journal": "Breast Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42828641/", "doi": "10.1007/s12282-026-01922-8", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "A significant subgroup estimate and a nonsignificant estimate in another subgroup do not establish an interaction. Overall and restricted luminal populations have different denominators. Treatment associations are observational, not chemotherapy benefit estimates. Full methods, endpoint components and adjustment details remain unreviewed behind subscription access.", "program": "breast", "kind": "observational", "level": "clinical", "result": "mixed", "by": "Codex (GPT-6)", "added": "2026-10-05", "label": "Lobular versus ductal outcomes — subtype interaction unconfirmed", "setting": "Retrospective surgical cohort; separate luminal subtype analyses", "population": "Stage I–III breast cancer overall; HR-positive/HER2-negative subsets for luminal analyses", "claim": "The overall cohort included 2,423 women, including 161 with lobular carcinoma. Adjusted invasive breast cancer-free survival for lobular versus ductal histology had HR 1.43 (95% CI 0.94–2.19; P=0.096). The luminal B-like subset had HR 1.47 (95% CI 1.03–2.09; P=0.033), but the histology-by-subtype interaction was not significant.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-Ki67Axilla26", "trial": null, "papers": [ { "key": "P-Ki67Axilla26", "pmid": "42829410", "title": "Lack of Utility of Ki-67 in Axillary Surgical Planning and Prognostication after Neoadjuvant Chemotherapy for Node-Positive Breast Cancer.", "journal": "Ann Surg Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42829410/", "doi": "10.1245/s10434-026-20397-7", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The change analysis is uncertain across statistical summaries; its confidence interval includes the null. It is not a randomized biomarker-guided surgery strategy. Nodal-response denominators, event counts, cutoffs and prespecified tests need full text, which was behind subscription access. No nodal-response proportion is inferred from the abstract. This study does not establish universal lack of Ki-67 utility.", "program": "breast", "kind": "observational", "level": "clinical", "result": "mixed", "by": "Codex (GPT-6)", "added": "2026-10-05", "label": "Ki-67 after neoadjuvant therapy — negative baseline and uncertain change findings", "setting": "Database analysis of biopsy and residual-tumor Ki-67 after neoadjuvant chemotherapy", "population": "Initially node-positive stage II/III breast cancer; residual-disease subset for change analysis", "claim": "Baseline Ki-67 did not predict nodal pathological complete response or recurrence in the reported multivariable analysis. In residual disease, decreased Ki-67 had a reported distant disease-free survival HR of 0.28 (95% CI 0.07–1.13), with Wilcoxon P=0.02 and log-rank P=0.057.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-MOUNTAINEER", "trial": "C-MOUNTAINEER", "papers": [ { "key": "P-MOUNTAINEER", "pmid": "37142372", "title": "Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.", "journal": "Lancet Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37142372/", "doi": "10.1016/S1470-2045(23)00150-X", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "The primary endpoint is a response rate in combined non-comparative cohorts; there is no chemotherapy or standard-care control, so no survival or comparative benefit is established. Response by HER2 level, duration of response and survival are not taken from this abstract. Results apply to RAS wild-type, locally assessed HER2-positive disease after chemotherapy; no extrapolation to RAS-mutant disease, earlier lines or gastric and breast cancer. No colorectal HER2 biomarker entry exists in the atlas, so none is linked.", "label": "MOUNTAINEER · tucatinib plus trastuzumab in HER2-positive colorectal cancer", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Chemotherapy-refractory, unresectable or metastatic", "population": "HER2-positive, RAS wild-type colorectal cancer", "claim": "In the phase 2 MOUNTAINEER study, 117 patients were enrolled (45 in the initial tucatinib plus trastuzumab cohort A; after expansion, 41 randomised to the combination in cohort B and 31 to tucatinib monotherapy in cohort C). Among 84 patients in cohorts A and B, the confirmed objective response rate by blinded independent central review was 38.1% (95% CI 27.7–49.3), with 3 complete and 29 partial responses, at the March 28, 2022 cutoff. In cohorts A and B diarrhoea occurred in 64% (55 of 86) and grade 3 or worse hypertension in 7%; no deaths were attributed to adverse events.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-MOUNTAINEER", "nct": "NCT03043313", "acronym": null, "title": "Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 117, "sponsor": "Seagen Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "National Cancer Institute (NCI)", "Academic and Community Cancer Research United" ], "hasResults": true, "start": "2017-06-23", "lastUpdate": "2024-11-26", "url": "https://clinicaltrials.gov/study/NCT03043313" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-DCRC01", "trial": "C-DCRC01", "papers": [ { "key": "P-DCRC01", "pmid": "33961795", "title": "Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33961795/", "doi": "10.1016/S1470-2045(21)00086-3", "errata": [] }, { "key": "P-DCRC01Final", "pmid": "37286557", "title": "Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer.", "journal": "Nat Commun", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37286557/", "doi": "10.1038/s41467-023-38032-4", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "Single-arm cohorts without a control; no comparative or survival benefit is established. The final-report abstract does not state which cohort the median survival and duration figures describe, so they are not attributed to a cohort here. The dose (6.4 mg/kg) differs from the 5.4 mg/kg used in breast cancer trials. Absence of responses in lower HER2 expression rests on small cohorts (15 and 18 patients). Interstitial lung disease is a material risk. No colorectal HER2 biomarker entry exists in the atlas, so none is linked.", "label": "DESTINY-CRC01 · trastuzumab deruxtecan by HER2 expression level in colorectal cancer", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "mixed", "setting": "After two or more previous regimens, metastatic", "population": "HER2-expressing, RAS and BRAF V600E wild-type metastatic colorectal cancer, in three cohorts by HER2 level", "claim": "In the phase 2 DESTINY-CRC01 trial of trastuzumab deruxtecan 6.4 mg/kg, the primary analysis reported a confirmed objective response by independent central review in 24 of 53 patients (45.3%, 95% CI 31.6–59.6) with HER2-positive tumours (cohort A: IHC 3+ or IHC 2+/ISH-positive). The final report, with 86 patients enrolled (53, 15 and 18 in cohorts A, B and C), found no responses in the IHC 2+/ISH-negative or IHC 1+ cohorts and reported median progression-free survival, overall survival and duration of response of 6.9, 15.5 and 7.0 months, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 8 patients (9.3%); the primary analysis recorded two grade 5 cases, the only treatment-related deaths at that time.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-DCRC01", "nct": "NCT03384940", "acronym": null, "title": "DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 86, "sponsor": "Daiichi Sankyo Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo", "AstraZeneca" ], "hasResults": true, "start": "2018-02-23", "lastUpdate": "2021-10-18", "url": "https://clinicaltrials.gov/study/NCT03384940" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-BEACON", "trial": "C-BEACON", "papers": [ { "key": "P-BEACON", "pmid": "31566309", "title": "Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.", "journal": "N Engl J Med", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31566309/", "doi": "10.1056/NEJMoa1908075", "errata": [] }, { "key": "P-BEACONOS", "pmid": "33503393", "title": "Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33503393/", "doi": "10.1200/JCO.20.02088", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label design. Primary endpoints compared the triplet with control; the doublet-versus-control survival comparison was a secondary endpoint, and these abstracts report no formal triplet-versus-doublet comparison. Median survival remained under one year in every group. Results apply to previously treated BRAF V600E disease, not first-line treatment or other BRAF alterations. BRAF and EGFR are not approved atlas targets, so no target is linked.", "label": "BEACON CRC · encorafenib plus cetuximab in BRAF V600E colorectal cancer", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After one or two previous regimens, metastatic", "population": "BRAF V600E-mutated metastatic colorectal cancer", "claim": "In the open-label phase 3 BEACON CRC trial, 665 patients were randomised 1:1:1 to encorafenib, binimetinib and cetuximab (triplet, n=224), encorafenib and cetuximab (doublet, n=220) or investigators' choice of cetuximab with irinotecan or FOLFIRI (control, n=221). At the prespecified interim analysis median overall survival was 9.0 versus 5.4 months for triplet versus control (HR 0.52, 95% CI 0.39–0.70) and 8.4 months for the doublet (HR versus control 0.60, 95% CI 0.45–0.79); confirmed response was 26% versus 2%. With 6 further months of follow-up, median overall survival was 9.3 months for the triplet (HR 0.60, 95% CI 0.47–0.75) and 9.3 months for the doublet (HR 0.61, 95% CI 0.48–0.77) versus 5.9 months for control; confirmed response rates were 26.8%, 19.5% and 1.8%. Grade 3 or higher adverse events occurred in 65.8%, 57.4% and 64.2%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-BEACON", "nct": "NCT02928224", "acronym": "BEACON CRC", "title": "Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 702, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [ "Merck KGaA, Darmstadt, Germany", "Pierre Fabre Medicament", "Ono Pharmaceutical Co., Ltd." ], "hasResults": true, "start": "2016-10-13", "lastUpdate": "2023-12-21", "url": "https://clinicaltrials.gov/study/NCT02928224" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-KN355", "trial": "B-KN355", "papers": [ { "key": "P-KN355", "pmid": "33278935", "title": "Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.", "journal": "Lancet", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/33278935/", "doi": "10.1016/S0140-6736(20)32531-9", "errata": [] }, { "key": "P-KN355OS", "pmid": "35857659", "title": "Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35857659/", "doi": "10.1056/NEJMoa2202809", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-B" ], "subtypes": [ "B-TNBC" ], "limits": "Benefit was statistically established only in the CPS ≥10 subgroup under a hierarchical testing plan; results for CPS ≥1 did not meet significance and the intention-to-treat population was not tested, so they do not support use regardless of PD-L1 score. The CPS assay and cut-off differ from the PD-L1 assays used in atezolizumab trials; scores are not interchangeable. Chemotherapy partner was investigator's choice. No extrapolation to early-stage disease.", "label": "KEYNOTE-355 · pembrolizumab plus chemotherapy by PD-L1 score", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First line, locally recurrent inoperable or metastatic", "population": "Previously untreated advanced triple-negative breast cancer; analysed by PD-L1 CPS ≥10, CPS ≥1 and intention to treat", "claim": "In the double-blind phase 3 KEYNOTE-355 trial, 847 patients were randomised 2:1 to pembrolizumab plus chemotherapy (n=566) or placebo plus chemotherapy (n=281). In patients with PD-L1 CPS ≥10, median progression-free survival was 9.7 versus 5.6 months (HR 0.65, 95% CI 0.49–0.86; primary objective met) and median overall survival 23.0 versus 16.1 months (HR 0.73, 95% CI 0.55–0.95; significance criterion met). With CPS ≥1, progression-free survival was 7.6 versus 5.6 months (HR 0.74, 95% CI 0.61–0.90; not significant under the prespecified boundary) and overall survival 17.6 versus 16.0 months (HR 0.86, 95% CI 0.72–1.04; not significant). In the intention-to-treat population the corresponding hazard ratios were 0.82 (95% CI 0.69–0.97) and 0.89 (95% CI 0.76–1.05), not formally tested. Grade 3–5 treatment-related adverse events occurred in 68.1% versus 66.9%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-KN355", "nct": "NCT02819518", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 882, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2016-07-27", "lastUpdate": "2024-11-27", "url": "https://clinicaltrials.gov/study/NCT02819518" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Dual primary endpoints: progression-free survival and overall survival in the PD-L1 CPS ≥10, CPS ≥1 and intention-to-treat populations (final overall survival analysis reported in the 2022 paper)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 847, "assessment": "not stated", "quote": "In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 … 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group." }, "effect": { "measure": "HR", "value": 0.73, "ci_low": 0.55, "ci_high": 0.95, "ci_level": "95%", "p": "two-sided P = 0.0185 [criterion for significance met]", "endpoint": "Overall survival, PD-L1 CPS ≥10 subgroup (final analysis, median follow-up 44.1 months)", "quote": "In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met])" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 68.1, "grade3plus_control_pct": 66.9, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "0.4% with pembrolizumab-chemotherapy vs none with placebo-chemotherapy", "quote": "Adverse events of grade 3, 4, or 5 that were related to the trial regimen occurred in 68.1% of the patients in the pembrolizumab-chemotherapy group and in 66.9% in the placebo-chemotherapy group, including death in 0.4% of the patients in the pembrolizumab-chemotherapy group and in no patients in the placebo-chemotherapy group." }, "takeaway_en": "In previously untreated advanced triple-negative breast cancer with PD-L1 CPS ≥10, adding pembrolizumab to chemotherapy lengthened median overall survival from 16.1 to 23.0 months (HR 0.73, 95% CI 0.55–0.95) and median progression-free survival from 5.6 to 9.7 months (HR 0.65). Grade 3–5 treatment-related adverse events were similar (68.1% vs 66.9%), with treatment-related death in 0.4% vs none, and the overall survival benefit was not significant in the CPS ≥1 group (HR 0.86) or tested in all patients (HR 0.89).", "takeaway_ko": "이전 치료력이 없는 진행성 삼중음성 유방암 중 PD-L1 CPS ≥10 환자에서 항암화학요법에 펨브롤리주맙을 추가하자 전체생존기간 중앙값이 16.1개월에서 23.0개월로 늘었습니다(위험비 0.73, 95% 신뢰구간 0.55–0.95). 무진행생존기간 중앙값도 5.6개월에서 9.7개월로 늘었습니다(위험비 0.65). 3–5등급 치료 관련 이상반응은 68.1%와 66.9%로 비슷했고 치료 관련 사망은 0.4%와 0%였습니다. CPS ≥1 군에서는 전체생존 이득이 유의하지 않았고(위험비 0.86), 전체 환자군에서는 공식 검정이 이루어지지 않았습니다(위험비 0.89).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ML2", "trial": "B-ML2", "papers": [ { "key": "P-ML2", "pmid": "27717303", "title": "Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27717303/", "doi": "10.1056/NEJMoa1609709", "errata": [ { "pmid": "30586508", "title": "Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/30586508/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-ML2OS", "pmid": "35263519", "title": "Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35263519/", "doi": "10.1056/NEJMoa2114663", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Overall survival was a key secondary endpoint tested hierarchically after progression-free survival. Population is postmenopausal women treated first line with an aromatase inhibitor; no extrapolation to premenopausal patients, fulvestrant partners, later lines or early breast cancer. Results for ribociclib are not evidence about other CDK4/6 inhibitors, and no cross-trial comparison is made. Subsequent therapies after progression are not described in these abstracts.", "label": "MONALEESA-2 · first-line ribociclib plus letrozole", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line for advanced disease, with letrozole", "population": "Postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer and no previous systemic therapy for advanced disease", "claim": "In the placebo-controlled phase 3 MONALEESA-2 trial, 668 patients were randomised to ribociclib or placebo, each with letrozole. At the preplanned interim analysis, investigator-assessed progression-free survival was longer with ribociclib (HR 0.56, 95% CI 0.43–0.72); the 18-month progression-free survival rate was 63.0% versus 42.2%. Grade 3 or 4 neutropenia occurred in 59.3% versus 0.9%, and discontinuation for adverse events in 7.5% versus 2.1%. At the protocol-specified final overall survival analysis after a median follow-up of 6.6 years, 181 of 334 patients had died in the ribociclib group and 219 of 334 in the placebo group; median overall survival was 63.9 versus 51.4 months (HR 0.76, 95% CI 0.63–0.93; two-sided P=0.008).", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-ML2", "nct": "NCT01958021", "acronym": "MONALEESA-2", "title": "Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 668, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2013-12-17", "lastUpdate": "2025-03-07", "url": "https://clinicaltrials.gov/study/NCT01958021" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 668, "assessment": "investigator", "quote": "In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. … The primary end point was investigator-assessed progression-free survival." }, "effect": { "measure": "HR", "value": 0.56, "ci_low": 0.43, "ci_high": 0.72, "ci_level": "95%", "p": "P=3.29×10-6", "endpoint": "Progression-free survival (preplanned interim analysis)", "quote": "The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10-6 for superiority)." }, "landmark": [ { "endpoint": "Progression-free survival rate", "timepoint": "18 months", "experimental_pct": 63, "control_pct": 42.2, "higher_is_better": true, "experimental_arm": "Ribociclib plus letrozole", "control_arm": "Placebo plus letrozole", "quote": "After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group.", "difference_pp": 20.8, "nnt": 5, "quote_note": "P-ML2, 2016 interim analysis; median follow-up 15.3 months" }, { "endpoint": "Overall response rate (patients with measurable disease at baseline)", "timepoint": "Interim analysis (median follow-up 15.3 months)", "experimental_pct": 52.7, "control_pct": 37.1, "higher_is_better": true, "experimental_arm": "Ribociclib plus letrozole", "control_arm": "Placebo plus letrozole", "quote": "In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001).", "difference_pp": 15.6, "nnt": 7, "quote_note": "P-ML2, 2016 interim analysis" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 7.5, "discontinuation_control_pct": 2.1, "treatment_related_deaths": null, "quote": "Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. … No new safety signals were observed." }, "takeaway_en": "In postmenopausal women with HR-positive, HER2-negative advanced breast cancer and no prior systemic therapy for advanced disease, adding ribociclib to letrozole raised the 18-month progression-free survival rate from 42.2% to 63.0%. At the final analysis it also lengthened median overall survival from 51.4 to 63.9 months (HR 0.76). The cost was more grade 3 or 4 neutropenia (59.3% vs 0.9%) and more discontinuation for adverse events (7.5% vs 2.1%).", "takeaway_ko": "진행성 질환에 대한 전신치료 경험이 없는 HR 양성, HER2 음성 진행성 유방암 폐경 후 여성에서 레트로졸에 리보시클립을 추가하면 18개월 무진행생존율이 42.2%에서 63.0%로 높아졌습니다. 최종 분석에서 전체생존기간 중앙값도 51.4개월에서 63.9개월로 연장되었습니다(HR 0.76). 대신 3–4등급 호중구감소증(59.3% 대 0.9%)과 이상반응으로 인한 치료 중단(7.5% 대 2.1%)이 더 많았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DB02", "trial": "B-DB02", "papers": [ { "key": "P-DB02", "pmid": "37086745", "title": "Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial.", "journal": "Lancet", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37086745/", "doi": "10.1016/S0140-6736(23)00725-0", "errata": [ { "pmid": "38070948", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/38070948/", "reviewed": true, "unresolvedIdentifier": false }, { "pmid": "38460989", "title": "Department of Error.", "url": "https://pubmed.ncbi.nlm.nih.gov/38460989/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Open-label design with a centrally reviewed primary endpoint. Overall survival figures are not given in this abstract and are not adopted here. Interstitial lung disease, including fatal cases, is a material risk. The comparator is capecitabine-based therapy, not another antibody-drug conjugate or tucatinib-based therapy; no cross-trial comparison is made. No extrapolation to HER2-low disease or earlier lines.", "label": "DESTINY-Breast02", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After trastuzumab emtansine, unresectable or metastatic", "population": "HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine", "claim": "In the open-label phase 3 DESTINY-Breast02 trial, 608 patients were randomised 2:1 to trastuzumab deruxtecan 5.4 mg/kg (n=406) or treatment of physician's choice (n=202; capecitabine with trastuzumab or lapatinib). Median progression-free survival by blinded independent central review was 17.8 months (95% CI 14.3–20.8) versus 6.9 months (95% CI 5.5–8.4) (HR 0.36, 95% CI 0.28–0.45). Grade 3 or higher treatment-emergent adverse events occurred in 53% versus 44%, and drug-related interstitial lung disease in 10% (42 patients, including two grade 5 deaths) versus less than 1%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-DB02", "nct": "NCT03523585", "acronym": null, "title": "DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 608, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "Daiichi Sankyo Co., Ltd.", "AstraZeneca" ], "hasResults": true, "start": "2018-08-01", "lastUpdate": "2026-02-27", "url": "https://clinicaltrials.gov/study/NCT03523585" }, "sources": 2, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival based on blinded independent central review in the full analysis set", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 608, "assessment": "blinded independent central review", "quote": "This randomised, open-label, multicentre, phase 3 trial was conducted at 227 sites … The primary endpoint was progression-free survival based on blinded independent central review in the full analysis set. … 608 patients were randomly assigned to receive trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment)." }, "effect": { "measure": "HR", "value": 0.36, "ci_low": 0.28, "ci_high": 0.45, "ci_level": "95%", "p": "p<0·0001", "endpoint": "Progression-free survival by blinded independent central review", "quote": "Median progression-free survival by blinded independent central review was 17·8 months (95% CI 14·3-20·8) in the trastuzumab deruxtecan group versus 6·9 months (5·5-8·4) in the treatment of physician's choice group (HR 0·36 [0·28-0·45]; p<0·0001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 53, "grade3plus_control_pct": 44, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Two grade 5 death events from drug-related interstitial lung disease in the trastuzumab deruxtecan group", "quote": "Grade 3 or higher treatment-emergent adverse events occurred in 213 (53%) patients receiving trastuzumab deruxtecan versus 86 (44%) receiving treatment of physician's choice; whereas drug-related interstitial lung disease occurred in 42 (10%; including two grade 5 death events) versus one (<1%)." }, "takeaway_en": "In patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan was compared with physician's choice of capecitabine plus trastuzumab or lapatinib. Median progression-free survival by blinded independent central review was 17.8 versus 6.9 months (HR 0.36). The trade-off was more grade 3 or higher adverse events (53% vs 44%) and drug-related interstitial lung disease in 10% versus less than 1%, including two grade 5 deaths.", "takeaway_ko": "트라스투주맙 엠탄신 치료 후 진행한 HER2 양성 절제 불가능 또는 전이성 유방암 환자에서 트라스투주맙 데룩스테칸을 의사 선택 치료(카페시타빈과 트라스투주맙 또는 라파티닙 병용)와 비교했으며, 맹검 독립 중앙 평가에 따른 무진행생존기간 중앙값은 17.8개월 대 6.9개월이었습니다(위험비 0.36). 대신 3등급 이상 이상반응이 더 많았고(53% 대 44%), 약물 관련 간질성 폐질환이 10% 대 1% 미만에서 발생했으며 그중 5등급 사망이 2건 있었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ACafterNAC26", "trial": null, "papers": [ { "key": "P-ACafterNAC26", "pmid": "42830450", "title": "Re-evaluating the role of adjuvant chemotherapy after neoadjuvant chemotherapy in resected gastric cancer.", "journal": "Oncologist", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42830450/", "doi": "10.1093/oncolo/oyag384", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Retrospective treatment selection cannot establish the benefit or safety of omitting postoperative chemotherapy. Nonsignificance is not equivalence, and subgroup differences do not establish an interaction. Postoperative fitness, time-related bias, adjustment, cutpoint selection and multiplicity require full methods; the publisher returned an access challenge. This is a chemotherapy question, not proof about postoperative immunotherapy.", "by": "Codex (GPT-6)", "added": "2026-10-06", "label": "Adjuvant chemotherapy after neoadjuvant therapy — mixed retrospective associations", "program": "gastric", "kind": "observational", "level": "clinical", "result": "mixed", "setting": "Adjuvant chemotherapy receipt after neoadjuvant chemotherapy and gastric resection", "population": "Resected gastric cancer after neoadjuvant chemotherapy; postoperative nodal subgroups analyzed separately", "claim": "Among 339 patients, 264 received adjuvant chemotherapy. In the whole cohort, median event-free survival was 7.0 versus 7.5 years (P=.089), and overall survival did not differ significantly. In the node-positive subgroup, receiving chemotherapy was associated with longer event-free survival (4.8 versus 2.7 years; P=.031), but not with significantly longer overall survival. No survival association was reported in the node-negative subgroup.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-MuscularTLS26", "trial": null, "papers": [ { "key": "P-MuscularTLS26", "pmid": "42830321", "title": "Gastric cancer tertiary lymphoid structures in the muscularis propria are associated with therapy resistance and promote immunosuppression.", "journal": "Nat Commun", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42830321/", "doi": "10.1038/s41467-026-77267-9", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The cohort excluded patients who never reached surgery and used heterogeneous anti-PD-1 regimens. Response labels derive from pathological regression, not RECIST progression. Spatial-score tests treated spots as independent, so patient-aware validation is still needed. Cohort linkage to a registered trial and overlap with other reports remain unverified. Human raw data require controlled, non-commercial access. Causal in vivo combination efficacy and independent clinical validation are not established.", "by": "Codex (GPT-6)", "added": "2026-10-06", "label": "Muscular gastric lymphoid structures — location, maturity and resistance", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Post-treatment gastric tissue observations with supporting cell and organoid experiments", "population": "Gastric surgical specimens after neoadjuvant anti-PD-1 plus chemotherapy; human tissue associations and in vitro mechanisms", "claim": "In surgical specimens from 71 patients, lymphoid structures in the muscularis propria of treatment-resistant gastric cancers had greater density and area and showed impaired maturation. PLA2G2A exposure promoted inflammatory fibroblast features in vitro and impaired B-cell differentiation and follicular helper T-cell survival. The proposed tumor-stroma-immune axis is a mechanistic hypothesis.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CDH17Payload26", "trial": null, "papers": [ { "key": "P-CDH17Payload26", "pmid": "42832380", "title": "Topoisomerase-Based CDH17 Antibody Drug Conjugates Overcome P-gp Resistance but Undergo Target Mediated Clearance in Colorectal Cancer.", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42832380/", "doi": "10.1158/1078-0432.CCR-26-2010", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "These are preclinical findings, without patient efficacy or survival outcomes. Model-specific target expression and pharmacokinetics limit extrapolation. Faster clearance is not proof of human off-tumor toxicity, and tumor activity does not establish a therapeutic window. Full methods, doses, antibody cross-reactivity and safety endpoints remain unreviewed because the publisher returned an access challenge. CDH17 lacks an approved atlas target entry.", "by": "Codex (GPT-6)", "added": "2026-10-06", "label": "CDH17 ADC payload choice — resistance advantage with a clearance constraint", "program": "colorectal", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "Colorectal cancer models with P-gp modulation and cross-model pharmacokinetic comparisons", "population": "Cancer models, human normal-tissue staining, human-CDH17-expressing mice and cynomolgus monkeys", "claim": "Exatecan-based CDH17 ADCs retained activity in P-gp-expressing colorectal models where MMAE-based ADCs lost activity; inhibiting P-gp restored MMAE activity. CDH17-targeted antibodies and ADCs cleared approximately four-fold faster in human-CDH17-expressing mice than in wild-type mice or cynomolgus monkeys. Normal gastrointestinal epithelial expression raises a translation constraint.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HashimotoOutcome21", "trial": null, "papers": [ { "key": "P-HashimotoOutcome21", "pmid": "34313737", "title": "Prevalence of Hashimoto Thyroiditis in Adults With Papillary Thyroid Cancer and Its Association With Cancer Recurrence and Outcomes.", "journal": "JAMA Netw Open", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34313737/", "doi": "10.1001/jamanetworkopen.2021.18526", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Retrospective, single centre, operated patients only. Thyroiditis was identified on the surgical specimen, so its timing relative to the cancer is unknown and the study cannot show that thyroiditis preceded or modified the tumour. The mortality estimate rests on 2 deaths in the thyroiditis group and has a wide interval. Patients with known thyroiditis may be examined more often and diagnosed with smaller tumours; earlier detection is not excluded by adjustment for stage features. The authors' wording of a protective role is an interpretation of an association, not a demonstrated effect.", "label": "Coexistent Hashimoto thyroiditis and papillary cancer outcomes · single-centre cohort", "setting": "Retrospective single-centre surgical cohort in China, 2001–2014; thyroiditis defined on postoperative pathology", "population": "Adults aged 18–75 with pathologically confirmed papillary thyroid cancer", "claim": "Of 9,210 patients with papillary thyroid cancer, 1,751 (19%) had coexistent Hashimoto thyroiditis on postoperative sections. Thyroiditis was associated with lower odds of a primary tumour of 4 cm or greater (adjusted OR 0.20, 95% CI 0.12–0.33), gross extrathyroidal extension (0.44, 0.36–0.54) and distant metastasis (0.17, 0.04–0.71). After a median follow-up of 85 months there were 131 cancer-related deaths, 2 of them in patients with thyroiditis; unadjusted 10-year disease-specific survival was 99.9% versus 96.6% and recurrence-free survival 92.0% versus 87.6%. After adjustment, thyroiditis was associated with lower cancer-related mortality (HR 0.19, 95% CI 0.05–0.76).", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AutoimmuneThyCa24", "trial": null, "papers": [ { "key": "P-AutoimmuneThyCa24", "pmid": "38149584", "title": "Association Between Eight Autoimmune Diseases and Thyroid Cancer: A Nationwide Cohort Study.", "journal": "Thyroid", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38149584/", "doi": "10.1089/thy.2023.0353", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Diagnoses come from insurance claims, not from uniform thyroid examination. The abstract does not report how often thyroid ultrasound or biopsy was done in each group; patients followed for thyroid disease are examined more, and Korea had very high thyroid screening intensity in this period, so detection differences can produce this pattern. Thyroid cancer histology is not separated in the abstract. Raised estimates for non-thyroid autoimmune diseases are compatible with either shared biology or more medical contact. An observational hazard ratio does not establish that thyroiditis causes cancer.", "label": "Autoimmune diseases and incident thyroid cancer · Korean nationwide cohort", "setting": "Retrospective matched cohort in the Korean National Health Insurance Service–National Sample Cohort; average follow-up 9.49 years", "population": "Patients with one of eight autoimmune diseases, including Hashimoto thyroiditis, and matched controls without autoimmune disease", "claim": "During follow-up, 138 thyroid cancers developed in the control group and 268 in the group with the eight autoimmune diseases. The adjusted hazard ratio for incident thyroid cancer was 2.10 (confidence interval 1.57–2.81) for Hashimoto thyroiditis and 2.67 (1.99–3.62) for Graves disease. Raised estimates were also reported for diseases outside the thyroid: inflammatory bowel disease 2.06 (1.50–2.83), vitiligo 1.71 (1.13–2.59) and rheumatoid arthritis 1.76 (1.07–2.90). Thyroid-specific autoimmune disease as a group had the highest estimate (2.37, 1.85–3.03).", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTYoungFollowup26", "trial": null, "papers": [ { "key": "P-HTYoungFollowup26", "pmid": "42319874", "title": "Risk of Thyroid Cancer in Children, Adolescents, and Young Adults with Hashimoto Thyroiditis: A 27-Year Follow-Up Study.", "journal": "Horm Res Paediatr", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42319874/", "doi": "10.1159/000553100", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Retrospective. Patients had scheduled ultrasound, while the abstract does not say how the control population was examined; more examination finds more nodules and small cancers, so the comparison with controls is not an unbiased risk ratio. Ten cancers give little precision. Median follow-up was under six years, so lifetime risk is not estimated. The abstract does not report tumour stage or outcome, and does not identify a subgroup in which cancer did not occur. A correlation with antibody level is not a threshold for individual prediction.", "label": "Hashimoto thyroiditis in children, adolescents and young adults · multicentre follow-up", "setting": "Retrospective analysis of patients followed in nine Italian paediatric endocrinology centres; TSH and free T4 yearly, ultrasound yearly with nodules and every 2 years without", "population": "1,050 adolescents and young adults with Hashimoto thyroiditis (825 female, 225 male); median follow-up 5.8 years (range 0.6–27.6)", "claim": "Among 1,050 patients, 245 nodules were detected (prevalence 23.3%, versus 4.7% in a matched control population). Thyroid cancer was found in 10 patients (0.95%, versus 0.37% in the control population): 8 papillary carcinomas and 2 follicular variants of papillary carcinoma. Ultrasound hypoechogenicity, thyroid peroxidase antibodies and free T4 at diagnosis predicted new nodules, and thyroid peroxidase antibodies correlated positively with the development of thyroid cancer.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-JATNodules08", "trial": null, "papers": [ { "key": "P-JATNodules08", "pmid": "18524742", "title": "Thyroid nodules and cancer in children and adolescents affected by autoimmune thyroiditis.", "journal": "Arch Pediatr Adolesc Med", "year": "2008", "url": "https://pubmed.ncbi.nlm.nih.gov/18524742/", "doi": "10.1001/archpedi.162.6.526", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Referral-centre case series without an unaffected comparison group, so it gives a frequency within followed patients, not a population risk. All cancers arose among patients with nodules. Eleven cancers and very wide intervals. Regular ultrasound increases detection. Follow-up length and outcomes after treatment are not given in the abstract. Features associated with cancer here are observations in a small series, not validated decision rules.", "label": "Juvenile autoimmune thyroiditis · nodules and cancer in six Italian centres", "setting": "Retrospective multicentre series; thyroid function every 6 to 12 months and ultrasound every 12 to 24 months", "population": "365 children and adolescents with juvenile autoimmune thyroiditis diagnosed at 3.6 to 17.0 years of age", "claim": "Thyroid nodules were found in 115 patients (31.5% of the series). Findings in 11 were consistent with papillary carcinoma (3.0% of the series), 5 of them with lymph node metastasis; papillary carcinoma was the only histotype. Fine-needle aspiration was done in 39 patients with a nodule of 1 cm or larger and in 4 with a smaller suspicious nodule; twenty-three patients had surgery. Growth of a nodule during levothyroxine therapy (OR 15.60; 95% CI 1.87–181.90) and lymphadenopathy (OR 5.44; 95% CI 1.05–30.50) were associated with cancer.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AITChildNodule22", "trial": null, "papers": [ { "key": "P-AITChildNodule22", "pmid": "35950619", "title": "Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules.", "journal": "Thyroid", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35950619/", "doi": "10.1089/thy.2022.0241", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The population is children referred to a specialist centre with a nodule large enough to biopsy, in whom about a quarter of nodules were malignant; it does not describe children with thyroiditis who have no nodule, and it is not a risk of developing cancer over time. Thyroiditis was defined by antibodies or ultrasound texture, which a tumour-related immune reaction could also produce. Cross-sectional design cannot order thyroiditis and cancer in time.", "label": "Autoimmune thyroiditis and malignancy among children who already have a thyroid nodule", "setting": "Cross-sectional study in an academic paediatric thyroid centre; nodules of 1 cm or larger that underwent fine-needle aspiration", "population": "385 patients under 19 years with 458 thyroid nodules; median age 15.5 years; 81% female", "claim": "Thyroid cancer was present in 108 nodules (24%). Autoimmune thyroiditis, present in 95 subjects (25%), was independently associated with thyroid cancer (multivariable OR 2.19, 95% CI 1.32–3.62). Cancer was also associated with younger age, nodule size and solitary nodules, but not with serum thyrotropin concentration. Thyroiditis was not associated with undergoing surgery, nor with the extent of local, regional or distant disease at diagnosis; among papillary carcinomas it was associated with the diffuse sclerosing variant (OR 4.74, CI 1.33–16.9).", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTTSHLT411", "trial": null, "papers": [ { "key": "P-HTTSHLT411", "pmid": "21565972", "title": "Hashimoto's thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine.", "journal": "Endocr Relat Cancer", "year": "2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21565972/", "doi": "10.1530/ERC-11-0028", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Cross-sectional and not randomised: patients were on levothyroxine for clinical reasons, so treated and untreated groups differ in ways the abstract does not adjust for. Everyone had nodules and was referred for cytology; the result does not describe thyroiditis without nodules. The authors' statement that treatment decreases clinically detectable carcinoma is an inference from an association; this study did not test levothyroxine as an intervention. Frequencies of 6–9% reflect a referral cytology population, not the general risk.", "label": "Nodular Hashimoto thyroiditis, TSH and levothyroxine · cytology series", "setting": "Single-centre analysis of patients with thyroid nodules evaluated by cytology; untreated patients and patients on levothyroxine analysed separately", "population": "Patients with nodular Hashimoto thyroiditis (n=1593) or nodular goitre with or without thyroid antibodies; 9824 untreated and 3914 under levothyroxine", "claim": "Among untreated patients, papillary carcinoma was more frequent in nodular Hashimoto thyroiditis (9.4%) than in nodular goitre without antibodies (6.4%) or with antibodies (6.5%), and median TSH was also higher (1.30 versus 0.71 and 0.70 μU/ml). Papillary carcinoma frequency was related to serum TSH (OR 1.111) and unrelated to anti-thyroperoxidase antibodies. In the levothyroxine-treated group, among patients with TSH below the median value (0.90 μU/ml), papillary carcinoma frequency did not differ between nodular Hashimoto thyroiditis and the two goitre groups.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-TSHThyCaMeta12", "trial": null, "papers": [ { "key": "P-TSHThyCaMeta12", "pmid": "22622023", "title": "Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis.", "journal": "J Clin Endocrinol Metab", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22622023/", "doi": "10.1210/jc.2012-1083", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The abstract does not state when TSH was measured relative to the cancer diagnosis; in the case-control and cross-sectional studies it pools, TSH may be a marker of the investigated population or a consequence of thyroid disease rather than a cause. The association weakened when autoimmunity was accounted for. An odds ratio per unit of TSH is not evidence that lowering TSH prevents cancer; the authors list suppression for prevention as a question for future research.", "label": "Serum TSH and thyroid cancer diagnosis · dose-response meta-analysis", "setting": "Systematic review and dose-response meta-analysis of prospective cohort, case-control and cross-sectional studies", "population": "28 studies with 42,032 subjects and 5,786 thyroid cancer cases", "claim": "The relationship between TSH and thyroid cancer was nonlinear. For TSH below 1 mU/liter the odds ratio for thyroid cancer was 1.72 (1.42, 2.07) per mU/liter; at 1 mU/liter and above it was 1.16 (1.12, 1.21) per mU/liter. Studies that controlled for autoimmunity reported the lowest estimates: 1.23 (1.02–1.47) per mU/liter below 2.5 mU/liter and 0.98 (0.89–1.09) at 2.5 mU/liter or greater.", "program": "thyroid", "kind": "analysis", "level": "literature", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AITCytology14", "trial": null, "papers": [ { "key": "P-AITCytology14", "pmid": "24892990", "title": "Nodules in autoimmune thyroiditis are associated with increased risk of thyroid cancer in surgical series but not in cytological series: evidence for selection bias.", "journal": "J Clin Endocrinol Metab", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24892990/", "doi": "10.1210/jc.2014-1302", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Adults with a mean age near 58, all with nodules; not informative about children or about thyroiditis without nodules. Cytology is not a final diagnosis, and most patients had no histology. The study shows that who is sent to surgery changes the apparent association; it does not prove that no association exists.", "label": "Nodules in autoimmune thyroiditis · cytological versus surgical series", "setting": "Consecutive patients undergoing fine-needle aspiration cytology for thyroid nodules at one centre, with a histologically confirmed subgroup", "population": "2504 consecutive patients (mean age 58.3 years); autoimmune thyroiditis with nodules in 14.9%", "claim": "Cytology suggestive or indicative of malignancy was found in 4.5% of patients with nodular autoimmune thyroiditis, no different from the rates in nodular Graves disease (5.6%) or nodular goitre without (5.0%) or with (4.3%) thyroid antibodies. In the subgroup with histological confirmation (14.3%), differentiated thyroid cancer was more frequent in the thyroiditis group (67.8% versus 40.0%, 37.2% and 36.9%; P = .01). Suspicious cytology was the indication for surgery in 60.7% of the thyroiditis group, more often than in the other groups.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTTaiwanCohort13", "trial": null, "papers": [ { "key": "P-HTTaiwanCohort13", "pmid": "24084773", "title": "Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study.", "journal": "Br J Cancer", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/24084773/", "doi": "10.1038/bjc.2013.597", "errata": [] } ], "pages": [ { "key": "chen2013-ht-cohort-fulltext", "title": "Chen et al., Br J Cancer 2013 — results passages from the open-access full text", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3817335/", "file": "data/sources/pages/chen2013-ht-cohort-fulltext.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Neither the abstract nor the passages read from the full text give thyroid cancer case counts, and the interval for the early period is extremely wide. An excess concentrated in the first years after a thyroid diagnosis is what intensified examination at that time would produce, and may include cancers already present; the abstract does not report examination frequency. Claims data cannot confirm how thyroiditis or cancer was established. The estimate is far larger than in other cohorts in this library and is not treated as a typical risk.", "label": "Cancer after a Hashimoto thyroiditis diagnosis · Taiwanese insurance cohort", "setting": "Retrospective cohort in the Taiwanese National Health Insurance Research Database, 1998–2010", "population": "1521 newly diagnosed Hashimoto thyroiditis patients and 6084 frequency-matched patients without it", "claim": "Overall cancer incidence in the Hashimoto cohort was 5.07 per 1000 person-years, 1.68 times that of the comparison cohort. The adjusted hazard ratio for thyroid cancer was 11.8 (the full text gives a 95% CI of 4.24–33.1). The thyroid cancer incidence rate ratio was highest in the first 3 years after diagnosis (48.4, 95% CI 35.0–66.3; adjusted HR 49.4, 95% CI 6.39–382.4). In the full text, the thyroid cancer incidence rate within 3 years of diagnosis was 30.6 versus 0.63 per 1000 person-years.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-TSHHTMR25", "trial": null, "papers": [ { "key": "P-TSHHTMR25", "pmid": "39645548", "title": "Elevated thyroid-stimulating hormone levels, independent of Hashimoto's thyroiditis, increase thyroid cancer risk: Insights from genetic and clinical evidence.", "journal": "Endocrine", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39645548/", "doi": "10.1007/s12020-024-04126-2", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The abstract reports no effect sizes or intervals. Mendelian randomization rests on assumptions about the genetic instruments that the abstract cannot verify, and absence of a significant genetic association is not proof of no effect. The survey part is cross-sectional. The authors' recommendation to control TSH with hormone replacement is their inference; it was not tested as an intervention.", "label": "Hashimoto thyroiditis, TSH and thyroid cancer · Mendelian randomization with a survey analysis", "setting": "Two-sample and multivariable Mendelian randomization using genome-wide association data, plus a cross-sectional analysis of a United States health survey", "population": "European and East Asian genome-wide association datasets; survey participants", "claim": "Genetically predicted Hashimoto thyroiditis showed no significant association with thyroid cancer risk in either population. Genetically predicted higher TSH was associated with higher risk of thyroid cancer and papillary thyroid carcinoma, and lower TSH with lower risk; multivariable analysis and the survey analysis pointed the same way. In the survey, Hashimoto thyroiditis was not significantly related to thyroid cancer prevalence.", "program": "thyroid", "kind": "genomics", "level": "computational", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTMR24", "trial": null, "papers": [ { "key": "P-HTMR24", "pmid": "39304132", "title": "Causality of Hashimoto's Thyroiditis to Thyroid Cancer: A 2-S Mendelian Randomization Study.", "journal": "Endocr Pract", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39304132/", "doi": "10.1016/j.eprac.2024.09.009", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Summary-level genetic analysis; conclusions depend on instrument validity. The confidence interval for the reverse-direction estimate is printed in malformed form in the abstract and is not adopted here. A reverse-direction signal is compatible with tumours provoking an immune reaction but does not establish it. Not informative about any individual.", "label": "Hashimoto thyroiditis and thyroid cancer · bidirectional Mendelian randomization", "setting": "Two-sample bidirectional Mendelian randomization with several estimators and sensitivity analyses", "population": "Genome-wide association data of European and East Asian descent", "claim": "No evidence was found of a causal effect of genetically predicted Hashimoto thyroiditis on thyroid cancer in either European or East Asian populations. In the reverse direction, genetically predicted thyroid cancer was associated with Hashimoto thyroiditis in the European population (odds ratio 1.0838).", "program": "thyroid", "kind": "genomics", "level": "computational", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTPTCReview13", "trial": null, "papers": [ { "key": "P-HTPTCReview13", "pmid": "23293329", "title": "Clinical Review: Hashimoto's thyroiditis and papillary thyroid carcinoma: is there a correlation?", "journal": "J Clin Endocrinol Metab", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/23293329/", "doi": "10.1210/jc.2012-2978", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Averages across heterogeneous studies, not a pooled estimate with an interval. Needle biopsy lacks definitive pathology, so some cancers are missed, as the authors note. Operated patients are selected for suspicion, which inflates the surgical figures. Neither figure is the risk for a person with thyroiditis: 1.20% describes people referred for biopsy of a nodule. Mostly adult data.", "label": "Hashimoto thyroiditis and papillary cancer · needle-biopsy versus surgical-specimen studies", "setting": "Systematic literature review; studies grouped into fine-needle aspiration biopsy studies and archival thyroidectomy specimen studies", "population": "8 fine-needle aspiration studies of 18 023 specimens and 8 archival thyroidectomy studies of 9 884 specimens", "claim": "The average prevalence of papillary thyroid cancer in patients with Hashimoto thyroiditis was 1.20% in the needle-biopsy studies and 27.56% in the thyroidectomy studies. The relative risk of finding papillary cancer in thyroiditis specimens ranged from .39 to 1.00 in the needle-biopsy group (average .69) and from 1.15 to 4.16 in the thyroidectomy studies (average 1.59). The authors found no clear evidence of a correlation and judged the thyroidectomy studies subject to selection bias.", "program": "thyroid", "kind": "analysis", "level": "literature", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTDTCMortalityKR24", "trial": null, "papers": [ { "key": "P-HTDTCMortalityKR24", "pmid": "38171210", "title": "Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.", "journal": "Endocrinol Metab (Seoul)", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38171210/", "doi": "10.3803/EnM.2023.1748", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Observational, adjusted for age and sex only in the main model; patients with thyroiditis had smaller tumours at diagnosis, which earlier detection could explain. The abstract does not say how thyroiditis was defined or how many patients had it. Lower mortality among cancer patients with thyroiditis is an association and does not show that thyroiditis protects. Adult registry data; not specific to children.", "label": "Hashimoto thyroiditis and death after differentiated thyroid cancer · Korean national survey with meta-analysis", "setting": "Retrospective cohort from the National Epidemiologic Survey of Thyroid cancer in Korea, with a meta-analysis adding eight selected studies", "population": "4,398 patients with differentiated thyroid cancer; median follow-up 15 years", "claim": "During a median follow-up of 15 years, 341 of 4,398 patients (7.8%) died, 91 (2.1%) from thyroid cancer. Coexisting Hashimoto thyroiditis was associated with smaller and less aggressive tumours and, after adjustment for age and sex, with lower risk of death from any cause (HR 0.71; 95% CI 0.52 to 0.96) and of thyroid cancer-related death (HR 0.33; 95% CI 0.14 to 0.77). In the meta-analysis the risk ratios were 0.24 (95% CI 0.13 to 0.47) for all-cause and 0.23 (95% CI 0.13 to 0.40) for thyroid cancer-related mortality.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTPTCMeta26", "trial": null, "papers": [ { "key": "P-HTPTCMeta26", "pmid": "41514331", "title": "The dual oncogenic and protective roles of hashimoto's thyroiditis in papillary thyroid carcinoma: a cohort-based meta-analysis.", "journal": "World J Surg Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41514331/", "doi": "10.1186/s12957-025-04184-4", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The abstract gives point estimates without intervals. Pooled surgical cohorts; thyroiditis is usually identified on the operative specimen. Mortality did not differ here, unlike the Korean registry analysis in this library. More multifocal and bilateral tumours is an unfavourable association alongside the favourable ones. Associations among people who already have cancer say nothing about who develops it.", "label": "Coexisting Hashimoto thyroiditis in papillary thyroid cancer · cohort-based meta-analysis", "setting": "Meta-analysis of cohort studies comparing papillary thyroid cancer patients with and without coexisting thyroiditis", "population": "Forty-one studies involving 67,901 patients", "claim": "Coexisting thyroiditis was associated with more multifocality (OR = 1.13) and bilaterality (OR = 1.20), and with less extrathyroidal extension (OR = 0.85), capsular invasion (OR = 0.73), central lymph node metastasis (OR = 0.75), distant metastasis (OR = 0.33) and recurrence (OR = 0.74). No significant differences were found for vascular invasion, lateral lymph node involvement or mortality. Thyroiditis was associated with a lower frequency of BRAF V600E mutation (OR = 0.55).", "program": "thyroid", "kind": "analysis", "level": "literature", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ATAPeds15", "trial": null, "papers": [ { "key": "P-ATAPeds15", "pmid": "25900731", "title": "Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.", "journal": "Thyroid", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25900731/", "doi": "10.1089/thy.2014.0460", "errata": [] } ], "pages": [ { "key": "ata-pediatric-2015-ait", "title": "American Thyroid Association paediatric guideline 2015 — passages on autoimmune thyroiditis (PMC full text)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4854274/", "file": "data/sources/pages/ata-pediatric-2015-ait.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A 2015 guideline based on evidence to April 2014 and on expert opinion; the single report it cites is the Italian series already in this library. It links ultrasound evaluation to examination findings and does not state a schedule of routine ultrasound for children with thyroiditis who have a normal examination. Later evidence in this library (2022, 2026) was not available to the task force. This record describes what the guideline says; it is not advice for an individual.", "label": "American Thyroid Association paediatric guideline · passage on autoimmune thyroiditis", "setting": "Guideline for children with thyroid nodules and differentiated thyroid cancer; literature reviewed through April 2014", "population": "Children and adolescents; the passage concerns those with autoimmune thyroiditis", "claim": "The guideline states that data on children with autoimmune thyroiditis are limited. It cites one report with a nodule prevalence perhaps as high as 30%, in which 7 of 11 papillary cancers were detected only by ultrasound, and says it is unclear how many of these would have become clinically important. For patients with autoimmune thyroiditis it advises evaluation by an experienced thyroid ultrasonographer when the thyroid examination is suspicious (a suspected nodule or significant gland asymmetry), especially with palpable cervical lymphadenopathy.", "program": "thyroid", "kind": "guideline", "level": "literature", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-BenignThyDK18", "trial": null, "papers": [ { "key": "P-BenignThyDK18", "pmid": "29590402", "title": "Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.", "journal": "J Clin Endocrinol Metab", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29590402/", "doi": "10.1210/jc.2017-02599", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The abstract gives no ratio for thyroiditis itself, so its size and its course over time cannot be stated from this record. Hospital-registry thyroiditis is not confirmed Hashimoto thyroiditis and misses patients managed outside hospital. Higher ratios soon after diagnosis are expected when a thyroid diagnosis leads to imaging. The abstract's list after 10 years and its conclusion about thyroiditis point in different directions and need the full text to reconcile. Adult-dominated national data.", "label": "Benign thyroid diseases and later thyroid cancer · Danish nationwide registry cohort", "setting": "Hospital and cancer registry linkage in Denmark, 1978 to 2013; standardized incidence ratios for differentiated thyroid cancer, excluding the first 12 months after the benign diagnosis", "population": "Patients with a hospital diagnosis of thyroiditis (n = 12,532), hypothyroidism (n = 63,143), hyperthyroidism (n = 85,169), goitre or adenoma, among 8,258,807 residents", "claim": "Standardized incidence ratios for differentiated thyroid cancer were significantly elevated for all benign thyroid diseases apart from hypothyroidism, and were higher in the earlier follow-up periods. With the first 10 years of follow-up excluded, the abstract lists hyperthyroidism (SIR = 2.00; 95% CI 1.32 to 2.92), nontoxic nodular goiter (SIR = 4.91; 95% CI 3.91 to 6.09), simple goiter, other goiter and adenoma as still positively associated; thyroiditis is not on that list. The authors conclude that the increased risk after thyroiditis could not be solely attributed to increased medical surveillance.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTChildKR21", "trial": null, "papers": [ { "key": "P-HTChildKR21", "pmid": "33894068", "title": "Thyroid nodules in childhood-onset Hashimoto's thyroiditis: Frequency, risk factors, follow-up course and genetic alterations of thyroid cancer.", "journal": "Clin Endocrinol (Oxf)", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33894068/", "doi": "10.1111/cen.14490", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Single referral centre, retrospective, short follow-up, nine cancers. Every patient had ultrasound, which finds nodules that examination alone would not. All cancers were in patients with nodules. No comparison group without thyroiditis. Absence of disease at a median of 3.4 years is not long-term outcome.", "label": "Childhood-onset Hashimoto thyroiditis · nodules, cancer and follow-up in Korea", "setting": "Retrospective single-centre cohort in an iodine-sufficient country; ultrasound evaluation with risk categories", "population": "213 patients (194 female), mean age 10.6 years at the diagnosis of Hashimoto thyroiditis", "claim": "Thyroid nodules were detected in 40 (18.8%) patients over a median follow-up of 3.4 years, usually after the onset of puberty; a family history of thyroid disease predicted nodule detection (hazard ratio 2.1). Papillary thyroid carcinoma was diagnosed in 9 patients (4.2% of all patients and 22.5% of those with nodules). Malignant nodules had higher ultrasound risk levels than benign nodules. None of the patients with cancer showed evidence of disease over a median follow-up of 3.4 years.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTChildTR21", "trial": null, "papers": [ { "key": "P-HTChildTR21", "pmid": "34126658", "title": "Clinical, biochemical, and radiological follow-up results of children and adolescents with Hashimoto's thyroiditis: a single-center experience.", "journal": "J Pediatr Endocrinol Metab", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34126658/", "doi": "10.1515/jpem-2021-0035", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Small single-centre series with three cancers and about two years of follow-up. The comparison with nodules outside thyroiditis is with published figures, not with a control group in the study. All cancers were in patients with nodules. Ultrasound schedule and the denominators for each step are not fully given in the abstract.", "label": "Children and adolescents with Hashimoto thyroiditis · single-centre follow-up in Türkiye", "setting": "Retrospective single-centre review of patients diagnosed between 2012 and 2018", "population": "Children and adolescents with Hashimoto thyroiditis; 75.9% girls; median age 12.5 years at first admission", "claim": "Among 196 patients followed regularly, the median follow-up was 2.1 years. A nodule was detected during ultrasonographic follow-up in 29 (13%) patients, and papillary thyroid carcinoma was found in 3 of those with nodules (10.3%). The authors state that the malignancy rate among nodules was no higher than that reported for nodules not associated with thyroiditis.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTChildKR18", "trial": null, "papers": [ { "key": "P-HTChildKR18", "pmid": "29595320", "title": "Thyroid nodules and cancer in children and adolescents affected by Hashimoto's thyroiditis.", "journal": "Br J Radiol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29595320/", "doi": "10.1259/bjr.20180014", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A small series of children who were sent for ultrasound, so it over-represents those with a clinical reason for imaging; 7.9% is not a risk for children with thyroiditis in general and is several times the figure in larger followed cohorts in this library. Seven cancers. The diffuse sclerosing variant infiltrates the gland and can itself produce antibodies and a thyroiditis-like appearance, so the direction of the association is uncertain. No follow-up outcome in the abstract.", "label": "Paediatric Hashimoto thyroiditis referred for ultrasound · nodules and cancer in Korea", "setting": "Retrospective review of patients who underwent thyroid ultrasonography at one institution, 2006 to 2016; thyroiditis defined by thyroid autoantibodies", "population": "89 paediatric and adolescent patients aged 3 to 18.0 years", "claim": "Thyroid nodules were found in 20 of the 89 patients (22.4%). Seven of the 89 patients (7.9%) had a confirmed malignancy, all papillary thyroid carcinoma; five were of the diffuse sclerosing variant and two were conventional. The malignancy rate among nodules was 35%.", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTIntrathyroidal17", "trial": null, "papers": [ { "key": "P-HTIntrathyroidal17", "pmid": "28696209", "title": "Hashimoto's thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer.", "journal": "Endocr Relat Cancer", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28696209/", "doi": "10.1530/ERC-17-0085", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Retrospective; thyroiditis was read from the surgical specimen, so its timing is unknown. Restricted to cancer confined to the thyroid. The authors themselves find that thyroiditis status does not improve prognostic specificity. An association with remission among people who already have cancer does not show protection, and says nothing about who develops cancer.", "label": "Hashimoto thyroiditis and outcome of intrathyroidal papillary cancer · multicentre study", "setting": "Multicentre retrospective observational study; thyroiditis detected on pathological assessment", "population": "301 papillary thyroid cancers with no evidence of extrathyroidal disease", "claim": "Thyroiditis was present in 42.5% of the cohort and was associated with smaller tumour size and fewer aggressive variants. It was associated with a higher rate of clinical remission (OR 4, 95% CI 1.78-8.94) and longer recurrence-free survival (P = 0.004); after adjustment the association remained (OR 3.28, 95% CI 1.39-7.72). The absence of thyroiditis performed poorly in identifying patients without remission (probability of no clinical remission 21.05%, 95% CI 15.20-27.93).", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HTLNDissect18", "trial": null, "papers": [ { "key": "P-HTLNDissect18", "pmid": "28906015", "title": "Influence of coexistent Hashimoto's thyroiditis on the extent of cervical lymph node dissection and prognosis in papillary thyroid carcinoma.", "journal": "Clin Endocrinol (Oxf)", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/28906015/", "doi": "10.1111/cen.13475", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Single-institution surgical cohort; all patients had total thyroidectomy with central dissection, so it does not describe smaller operations or observation. Lymph node spread was as frequent with thyroiditis as without it, which differs from pooled analyses in this library. Thyroiditis timing relative to the cancer is unknown.", "label": "Coexistent Hashimoto thyroiditis, extent of node dissection and recurrence · Korean surgical cohort", "setting": "Retrospective cohort of patients who had total thyroidectomy with central compartment neck dissection", "population": "1369 patients with papillary thyroid carcinoma", "claim": "Thyroiditis did not lower the risk of cervical lymph node metastasis (61.6% versus 65.1%, P = .292). Patients with thyroiditis had more lymph nodes removed (11 versus 8). After adjustment for other clinicopathological factors, thyroiditis was negatively associated with structural persistent or recurrent disease (HR 0.39, 95% CI 0.18-0.87).", "program": "thyroid", "kind": "observational", "level": "clinical", "result": "descriptive", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-A6", "trial": null, "papers": [ { "key": "P-TCGATHCA14", "pmid": "25417114", "title": "Integrated genomic characterization of papillary thyroid carcinoma.", "journal": "Cell", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25417114/", "doi": "10.1016/j.cell.2014.09.050", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Cross-sectional association among surgically treated patients who already have cancer; it says nothing about who develops cancer. Thyroiditis is a site-reported history field, not uniform pathology review, and unrecorded thyroiditis counts as absent. No adjustment for age, sex, histological variant or site. The direction was expected from published pooled analyses. Internal reanalysis, not an external replication or experiment.", "label": "A6 · BRAF V600E by recorded lymphocytic thyroiditis in TCGA papillary thyroid cancer", "program": "thyroid", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A6", "setting": "Prespecified reanalysis of public TCGA data; plan locked before the mutation file was retrieved", "population": "TCGA papillary thyroid cancer patients with a recorded thyroid-disorder history and a sequenced primary tumour", "claim": "The BRAF hotspot mutation named in the plan was somewhat less frequent in patients with recorded lymphocytic thyroiditis than in those without, but the prespecified two-sided exact test and the interval for the difference did not establish a difference; the result is inconclusive. Group sizes, counts, the interval and the test are in the linked analysis record.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": { "id": "A6", "title": "BRAF V600E frequency by recorded lymphocytic thyroiditis in TCGA papillary thyroid cancer", "retrieved": "2026-10-06", "method": "Patients with a recorded thyroid-disorder history and a sequenced primary tumour; exposure is recorded lymphocytic thyroiditis; outcome is BRAF p.V600E in the primary tumour; two-sided Fisher exact test, Newcombe-Wilson interval for the difference and Wilson marginal intervals." } }, { "id": "U-A7", "trial": null, "papers": [ { "key": "P-YaegerCRC18", "pmid": "29316426", "title": "Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer.", "journal": "Cancer Cell", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29316426/", "doi": "10.1016/j.ccell.2017.12.004", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "A molecular co-occurrence pattern in one institution's series, expected from published reports including the source publication; it is not a treatment effect and not an external replication. Amplification is the discrete copy-number call, not the immunohistochemistry and in-situ hybridisation definition used in HER2 trials. No adjustment for tumour side, microsatellite status or treatment.", "label": "A7 · ERBB2 amplification by RAS/BRAF status in MSK metastatic colorectal cancer", "program": "colorectal", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A7", "setting": "Prespecified reanalysis of a public single-institution targeted-panel series; plan locked before the mutation and copy-number files were retrieved", "population": "Patients with metastatic colorectal cancer, one sample per patient with the primary tumour preferred", "claim": "High-level ERBB2 amplification was more frequent in tumours without a RAS or BRAF hotspot mutation than in tumours with one, and the prespecified exact test and interval for the difference supported that direction. Amplification was uncommon in both groups. Group sizes, counts, the interval and the test are in the linked analysis record.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 2, "corrections": 0, "analysisRecord": { "id": "A7", "title": "ERBB2 amplification by RAS/BRAF status in MSK metastatic colorectal cancer", "retrieved": "2026-10-06", "method": "One sample per patient, primary tumour preferred; RAS/BRAF mutant means a KRAS or NRAS missense mutation at codon 12, 13, 59, 61, 117 or 146 or BRAF V600E; outcome is high-level ERBB2 amplification in the discrete copy-number profile; two-sided Fisher exact test, Newcombe-Wilson interval for the difference and Wilson marginal intervals." } }, { "id": "U-OPRA", "trial": "C-OPRA", "papers": [ { "key": "P-OPRA22", "pmid": "35483010", "title": "Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35483010/", "doi": "10.1200/JCO.22.00032", "errata": [] }, { "key": "P-OPRA24", "pmid": "37883738", "title": "Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37883738/", "doi": "10.1200/JCO.23.01208", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Each group was compared with a historical disease-free survival rate, not with a randomised group assigned to immediate surgery, so the trial does not show that watch-and-wait is as safe as surgery. Entry into watch-and-wait depended on clinical response assessment, which is not a pathological complete response. The comparison of the two chemotherapy sequences for TME-free survival is a secondary end point. Both abstracts are one trial. No extrapolation to colon cancer or to patients selected by a blood test.", "label": "OPRA · watch-and-wait after total neoadjuvant therapy", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "descriptive", "setting": "Total neoadjuvant therapy, then watch-and-wait or total mesorectal excision by response", "population": "Stage II or III rectal adenocarcinoma", "claim": "In the randomised phase II OPRA trial, 324 patients received induction chemotherapy then chemoradiotherapy (n = 158) or chemoradiotherapy then consolidation chemotherapy (n = 166). Patients with a complete or near-complete response were offered watch-and-wait; total mesorectal excision (TME) was recommended for an incomplete response. Three-year disease-free survival was 76% in both groups, in line with the historical rate of 75%. At a median follow-up of 5.1 years, 5-year disease-free survival was 71% and 69% (P = .68) and TME-free survival was 39% versus 54% (P = .012). Of 81 patients with regrowth, 94% had regrowth within 2 years and 99% within 3 years. Disease-free survival was 64% both for patients who had TME after restaging and for those who had TME after regrowth.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-OPRA", "nct": "NCT02008656", "acronym": null, "title": "Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 358, "sponsor": "Memorial Sloan Kettering Cancer Center", "sponsorClass": "OTHER", "collaborators": [ "Colon and Rectal Surgery Inc.", "The Cleveland Clinic", "John Muir Health", "Oregon Health and Science University", "St. Joseph Hospital of Orange", "University of California, Irvine", "University of California, San Francisco", "University of Chicago", "University of South Florida", "University of Vermont", "University of Washington", "Medstar Health Research Institute", "Washington University School of Medicine", "Creighton University Medical Center", "The Methodist Hospital Research Institute", "University of Rochester", "University of Virginia", "St. Paul's Hospital", "St. Joseph, Florida", "Cleveland Clinic Florida", "University of Colorado, Denver", "University of Michigan" ], "hasResults": false, "start": "2013-11", "lastUpdate": "2026-08-24", "url": "https://clinicaltrials.gov/study/NCT02008656" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-FOxTROT", "trial": "C-FOxTROT", "papers": [ { "key": "P-FOxTROT23", "pmid": "36657089", "title": "Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial.", "journal": "J Clin Oncol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36657089/", "doi": "10.1200/JCO.22.00046", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-MSI-C" ], "subtypes": [], "limits": "The primary end point combines residual disease at surgery with recurrence at 2 years; survival is not reported in this abstract. Staging was radiological, so some patients had lower-risk disease than assumed. The mismatch repair-deficient finding is a subgroup observation without numbers in the abstract and is not a test of immunotherapy. Open-label design. No extrapolation to rectal cancer.", "label": "FOxTROT · preoperative chemotherapy for operable colon cancer", "program": "colorectal", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Six weeks of chemotherapy before surgery versus all chemotherapy after surgery", "population": "Radiologically staged T3-4, N0-2, M0 operable colon cancer", "claim": "In the international randomised FOxTROT trial, patients were allocated 2:1 to 6 weeks of preoperative and 18 weeks of postoperative oxaliplatin-fluoropyrimidine (n = 699) or to 24 weeks of postoperative treatment (n = 354). The primary end point, residual disease or recurrence within 2 years, occurred in 16.9% (118 of 699) versus 21.5% (76 of 354) (rate ratio 0.72, 95% CI 0.54 to 0.98; P = .037). Resection was histopathologically complete in 94% (648 of 686) versus 89% (311 of 351). Thirty patients (4.3%) allocated to preoperative chemotherapy needed expedited surgery for obstructive symptoms. Adding panitumumab in RAS-wildtype tumours did not enhance the benefit, and little benefit was seen in mismatch repair-deficient tumours.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-FOxTROT", "nct": "NCT00647530", "acronym": "FOxTROT", "title": "Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery", "status": "UNKNOWN", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 1053, "sponsor": "University of Birmingham", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2008-05-15", "lastUpdate": "2019-05-17", "url": "https://clinicaltrials.gov/study/NCT00647530" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CM142", "trial": "C-CM142", "papers": [ { "key": "P-CM142mono", "pmid": "28734759", "title": "Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.", "journal": "Lancet Oncol", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28734759/", "doi": "10.1016/S1470-2045(17)30422-9", "errata": [ { "pmid": "28884691", "title": "Correction to Lancet Oncol 2017; 18: 1182-91.", "url": "https://pubmed.ncbi.nlm.nih.gov/28884691/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-CM142combo", "pmid": "29355075", "title": "Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.", "journal": "J Clin Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29355075/", "doi": "10.1200/JCO.2017.76.9901", "errata": [] }, { "key": "P-CM142first", "pmid": "34637336", "title": "First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/34637336/", "doi": "10.1200/JCO.21.01015", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "Non-randomised cohorts without a control group; the cohorts differ in prior treatment and dosing, so the response rates are not a comparison of monotherapy with combination therapy. Response was investigator-assessed and mismatch repair status was assessed locally. Durable response in metastatic disease does not establish a cure fraction. The three abstracts are one study. No extrapolation to microsatellite-stable colorectal cancer.", "label": "CheckMate 142 · nivolumab with or without ipilimumab", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "positive", "setting": "Metastatic disease: previously treated cohorts and a first-line cohort", "population": "dMMR or MSI-H metastatic colorectal cancer", "claim": "In the open-label phase 2 CheckMate 142 study, nivolumab alone gave an investigator-assessed objective response in 23 of 74 previously treated patients (31.1%, 95% CI 20.8–42.9), with disease control for 12 weeks or longer in 69%. Nivolumab plus ipilimumab in 119 previously treated patients gave an objective response rate of 55% (95% CI 45.2 to 63.8) at a median follow-up of 13.4 months; 12-month progression-free survival was 71% and overall survival 85%, and grade 3 to 4 treatment-related adverse events occurred in 32%. In the first-line cohort (N = 45) given nivolumab plus low-dose ipilimumab, the objective response rate was 69% (95% CI 53 to 82) with a 13% complete response rate at a median follow-up of 29.0 months; 24-month progression-free and overall survival rates were 74% and 79%, and grade 3-4 treatment-related adverse events occurred in 22%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "C-CM142", "nct": "NCT02060188", "acronym": "CheckMate142", "title": "A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 385, "sponsor": "Bristol-Myers Squibb", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-03-12", "lastUpdate": "2025-11-06", "url": "https://clinicaltrials.gov/study/NCT02060188" }, "sources": 4, "corrections": 1, "analysisRecord": null }, { "id": "U-PHERGain", "trial": "B-PHERGain", "papers": [ { "key": "P-PHERGain21", "pmid": "34019819", "title": "Chemotherapy de-escalation using an (18)F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial.", "journal": "Lancet Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34019819/", "doi": "10.1016/S1470-2045(21)00122-4", "errata": [] }, { "key": "P-PHERGain24", "pmid": "38582092", "title": "3-year invasive disease-free survival with chemotherapy de-escalation using an (18)F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial.", "journal": "Lancet", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38582092/", "doi": "10.1016/S0140-6736(24)00054-0", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The two groups were not designed to be compared; survival in group B was tested against a prespecified threshold, not against group A. About a third of patients omitted chemotherapy; the rest of group B still received it before or after surgery, so the result describes a strategy rather than chemotherapy-free treatment for all. Three-year follow-up is short for HER2-positive disease with hormone receptor-positive tumours. Both abstracts are one trial.", "label": "PHERGain · PET- and response-adapted chemotherapy de-escalation", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Neoadjuvant trastuzumab and pertuzumab, with chemotherapy added by PET response and pathological response", "population": "Centrally confirmed HER2-positive, stage I-IIIA operable breast cancer with a PET-evaluable lesion", "claim": "In the randomised, non-comparative phase 2 PHERGain trial, 71 patients were allocated to docetaxel, carboplatin, trastuzumab and pertuzumab (group A) and 285 to trastuzumab and pertuzumab with treatment adapted to PET after two cycles (group B). In group B, 227 of 285 (80%) were PET responders, and 86 of 227 (37.9%, 95% CI 31.6–44.5) had a pathological complete response without chemotherapy. PET responders without a pathological complete response then received chemotherapy after surgery. At a median follow-up of 43.3 months, 3-year invasive disease-free survival in group B was 94.8% (95% CI 91.4–97.1), meeting the primary end point. Treatment-related grade 3 or higher adverse events occurred in 62% of group A versus 33% of group B, and serious adverse events in 28% versus 14%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-PHERGain", "nct": "NCT03161353", "acronym": "PHERGain", "title": "Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy.", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 377, "sponsor": "MedSIR", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2017-06-26", "lastUpdate": "2025-04-23", "url": "https://clinicaltrials.gov/study/NCT03161353" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Coprimary: pathological complete response (ypT0/is ypN0) among group B 18F-FDG-PET responders, and 3-year invasive disease-free survival in group B", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "2", "randomized": true, "blinding": "open-label", "n_randomized": 356, "assessment": "not stated", "quote": "PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio … a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B).", "quote_note": "2021 paper: \"a multicentre, randomised, open-label, non-comparative, phase 2 trial\"; pathological complete response \"as determined by a local pathologist\"; \"Centrally reviewed 18F-FDG-PET scans\"" }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": null, "endpoint": null, "quote": null }, "landmark": [], "harms": { "grade3plus_experimental_pct": 33, "grade3plus_control_pct": 62, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "No deaths were reported during neoadjuvant treatment (2021 report); deaths over longer follow-up not reported in the abstracts", "quote": "Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). … No deaths were reported during neoadjuvant treatment.", "quote_note": "2024 paper, median follow-up 43·3 months; 2021 paper" }, "takeaway_en": "In this non-comparative phase 2 trial of centrally confirmed HER2-positive stage I-IIIA operable breast cancer, 71 patients received docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP; group A), and 285 received trastuzumab and pertuzumab with treatment adapted to PET after two cycles (group B). In group B, 86 of 227 PET responders (37.9%) had a pathological complete response without chemotherapy, and 3-year invasive disease-free survival for the whole PET- and response-adapted group B was 94.8%, with no between-group efficacy comparison reported; treatment-related grade 3 or higher adverse events occurred in 62% of group A versus 33% of group B, and serious adverse events in 28% versus 14%.", "takeaway_ko": "이 비비교 2상 시험은 중앙 확인된 HER2 양성 I-IIIA기 수술 가능 유방암 환자를 대상으로 했습니다. 71명은 도세탁셀·카보플라틴·트라스투주맙·퍼투주맙(TCHP; A군)을, 285명은 트라스투주맙·퍼투주맙을 투여받고 2주기 후 PET 결과에 따라 치료를 조정했습니다(B군). B군의 PET 반응자 227명 중 86명(37.9%)이 항암화학요법 없이 병리학적 완전관해에 도달했고, PET 및 반응 적응 전략을 적용한 B군 전체의 3년 침습적 무질병 생존율은 94.8%였으나 두 군 간 유효성 비교는 보고되지 않았습니다. 치료 관련 3등급 이상 이상반응은 A군 62%, B군 33%였고, 중대한 이상반응은 각각 28%와 14%였습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "no confidence interval for the primary effect in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-APHINITY", "trial": "B-APHINITY", "papers": [ { "key": "P-APHINITY17", "pmid": "28581356", "title": "Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.", "journal": "N Engl J Med", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28581356/", "doi": "10.1056/NEJMoa1703643", "errata": [ { "pmid": "28700263", "title": "Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/28700263/", "reviewed": true, "unresolvedIdentifier": false }, { "pmid": "30338958", "title": "Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations; Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/30338958/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-APHINITY21", "pmid": "33539215", "title": "Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33539215/", "doi": "10.1200/JCO.20.01204", "errata": [] }, { "key": "P-APHINITY24", "pmid": "39259927", "title": "Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39259927/", "doi": "10.1200/JCO.23.02505", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The invasive-disease-free survival benefit was established for the whole trial population; the node-positive and node-negative results are cohort analyses. Overall survival has not reached significance at three interim analyses. The absolute difference in the whole population at 3 years was under 1 percentage point. The three abstracts are one trial. No extrapolation to patients treated with neoadjuvant therapy or to residual disease after it.", "label": "APHINITY · adjuvant pertuzumab added to trastuzumab and chemotherapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Adjuvant, one year of pertuzumab or placebo with trastuzumab and chemotherapy", "population": "Node-positive or high-risk node-negative HER2-positive operable breast cancer", "claim": "In the placebo-controlled phase 3 APHINITY trial, 2400 patients were assigned to pertuzumab and 2405 to placebo. At the primary analysis, an invasive-disease event occurred in 171 patients (7.1%) versus 210 (8.7%) (hazard ratio 0.81, 95% CI 0.66 to 1.00; P=0.045); 3-year invasive-disease-free survival was 94.1% versus 93.2%. The hazard ratio was 0.77 (95% CI 0.62 to 0.96) in node-positive disease and 1.13 (95% CI 0.68 to 1.86) in node-negative disease. Grade 3 or higher diarrhoea occurred in 9.8% versus 3.7%. At 8.4 years of median follow-up, 8-year overall survival was 92.7% versus 92.0% (HR 0.83, 95% CI 0.68 to 1.02; P = .078, above the 0.006 significance threshold). In the node-positive cohort, 8-year invasive disease-free survival was 86.1% versus 81.2% (HR 0.72, 95% CI 0.60 to 0.87); in the node-negative cohort the placebo group had 8-year invasive disease-free survival of 93.3%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-APHINITY", "nct": "NCT01358877", "acronym": "APHINITY", "title": "A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 4804, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "Genentech, Inc.", "Breast International Group" ], "hasResults": true, "start": "2011-11-08", "lastUpdate": "2025-11-28", "url": "https://clinicaltrials.gov/study/NCT01358877" }, "sources": 4, "corrections": 2, "analysisRecord": null, "clinical": { "primary_endpoint": "Invasive-disease-free survival (iDFS)", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": null, "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab." }, "effect": { "measure": "HR", "value": 0.81, "ci_low": 0.66, "ci_high": 1, "ci_level": "95%", "p": "0.045", "endpoint": "Invasive-disease-free survival (primary analysis)", "quote": "Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045)." }, "landmark": [ { "endpoint": "Invasive disease-free survival (intent-to-treat)", "timepoint": "6 years", "experimental_pct": 91, "control_pct": 88, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively.", "difference_pp": 3, "nnt": 34, "quote_note": "P-APHINITY21, 74 months median follow-up; the most recent whole-population iDFS landmark reported for both arms" }, { "endpoint": "Overall survival (intent-to-treat)", "timepoint": "8 years", "experimental_pct": 92.7, "control_pct": 92, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .078, above the 0.006 significance threshold).", "difference_pp": 0.7, "nnt": 143, "quote_note": "P-APHINITY24, 8.4 years median follow-up; most recent" }, { "endpoint": "Invasive disease-free survival (node-positive cohort)", "timepoint": "8 years", "experimental_pct": 86.1, "control_pct": 81.2, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]).", "difference_pp": 4.9, "nnt": 21, "quote_note": "P-APHINITY24, 8.4 years median follow-up; most recent" }, { "endpoint": "Invasive disease-free survival (node-negative cohort)", "timepoint": "3 years", "experimental_pct": 97.5, "control_pct": 98.4, "higher_is_better": true, "experimental_arm": "Pertuzumab + trastuzumab + chemotherapy", "control_arm": "Placebo + trastuzumab + chemotherapy", "quote": "In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64).", "difference_pp": -0.9, "nnt": null, "nnt_label": "favours control", "quote_note": "P-APHINITY17 primary analysis; the most recent node-negative figures reported for both arms. P-APHINITY24 reports only the placebo 8-year iDFS of 93.3%", "nnh": 112 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). … Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen.", "quote_note": "Overall grade ≥3 adverse-event and discontinuation rates are not reported in the abstracts. The 9.8% vs 3.7% figures apply to diarrhea only" }, "takeaway_en": "In patients with node-positive or high-risk node-negative HER2-positive operable breast cancer, adding 1 year of pertuzumab to adjuvant trastuzumab and chemotherapy raised 6-year invasive disease-free survival from 88% to 91% (HR 0.76). The gain was concentrated in node-positive disease (8-year iDFS 86.1% vs 81.2%), there was no benefit in node-negative disease, and 8-year overall survival was 92.7% vs 92.0%, which was not statistically significant. The main harm was grade 3 or higher diarrhea (9.8% vs 3.7%), mostly during chemotherapy, while primary cardiac events stayed below 1% in both groups.", "takeaway_ko": "림프절 양성 또는 고위험 림프절 음성 HER2 양성 수술 가능 유방암 환자에서, 보조 트라스투주맙 및 항암화학요법에 퍼투주맙 1년을 추가하자 6년 침습적 무질병 생존율이 88%에서 91%로 높아졌습니다(위험비 0.76). 이 효과는 림프절 양성 환자에 집중되었고(8년 iDFS 86.1% 대 81.2%), 림프절 음성 환자에서는 이득이 없었으며, 8년 전체 생존율은 92.7% 대 92.0%로 통계적으로 유의하지 않았습니다. 주된 위해는 주로 항암화학요법 기간에 발생한 3등급 이상 설사(9.8% 대 3.7%)였고, 일차 심장 사건은 두 군 모두 1% 미만이었습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PALOMA3", "trial": "B-PALOMA3", "papers": [ { "key": "P-PALOMA3", "pmid": "26030518", "title": "Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/26030518/", "doi": "10.1056/NEJMoa1505270", "errata": [] }, { "key": "P-PALOMA3OS", "pmid": "30345905", "title": "Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30345905/", "doi": "10.1056/NEJMoa1810527", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Progression-free survival was the primary end point and was met; the overall survival difference in the whole trial population was not significant. The endocrine-sensitive result is a stratification-factor subgroup and does not replace the whole-population test. Results for palbociclib are not evidence about other CDK4/6 inhibitors, and no cross-trial comparison is made. Both abstracts are one trial. No extrapolation to first-line or adjuvant use.", "label": "PALOMA-3 · palbociclib plus fulvestrant after endocrine therapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Advanced disease that relapsed or progressed during prior endocrine therapy", "population": "HR-positive, HER2-negative advanced breast cancer", "claim": "In the phase 3 PALOMA-3 trial, 521 patients were randomised 2:1 to palbociclib plus fulvestrant or placebo plus fulvestrant. At the preplanned interim analysis, median progression-free survival was 9.2 versus 3.8 months (hazard ratio 0.42, 95% CI 0.32 to 0.56; P<0.001). Grade 3 or 4 neutropenia occurred in 62.0% versus 0.6%. In the prespecified overall survival analysis, median overall survival was 34.9 versus 28.0 months (hazard ratio 0.81, 95% CI 0.64 to 1.03; P=0.09). Among 410 patients with sensitivity to previous endocrine therapy, median overall survival was 39.7 versus 29.7 months (hazard ratio 0.72, 95% CI 0.55 to 0.94). CDK4/6 inhibitor treatment after the trial regimen occurred in 16% of the placebo group. Median time to chemotherapy was 17.6 versus 8.8 months (hazard ratio 0.58, 95% CI 0.47 to 0.73).", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "B-PALOMA3", "nct": "NCT01942135", "acronym": null, "title": "Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 521, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca" ], "hasResults": true, "start": "2013-09-26", "lastUpdate": "2024-04-04", "url": "https://clinicaltrials.gov/study/NCT01942135" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 521, "assessment": "investigator", "quote": "This phase 3 study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. … The primary end point was investigator-assessed progression-free survival." }, "effect": { "measure": "HR", "value": 0.42, "ci_low": 0.32, "ci_high": 0.56, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (preplanned interim analysis)", "quote": "The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib-fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 2.6, "discontinuation_control_pct": 1.7, "treatment_related_deaths": null, "quote": "The most common grade 3 or 4 adverse events in the palbociclib-fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs. 0.6%) … Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo." }, "takeaway_en": "In 521 patients with HR-positive, HER2-negative advanced breast cancer that relapsed or progressed during prior endocrine therapy, palbociclib plus fulvestrant improved median progression-free survival compared with placebo plus fulvestrant, 9.2 versus 3.8 months (hazard ratio 0.42), but the overall survival difference in the whole trial was not significant (34.9 versus 28.0 months; hazard ratio 0.81, 95% CI 0.64 to 1.03). The main harm was grade 3 or 4 neutropenia in 62.0% versus 0.6%, while febrile neutropenia occurred in 0.6% in both groups and discontinuation due to adverse events occurred in 2.6% versus 1.7%.", "takeaway_ko": "이전 내분비요법 중 재발하거나 진행한 호르몬수용체 양성, HER2 음성 진행성 유방암 환자 521명에서 팔보시클립과 풀베스트란트 병용은 위약과 풀베스트란트에 비해 무진행생존기간 중앙값을 9.2개월 대 3.8개월로 연장했습니다(위험비 0.42). 그러나 전체 환자의 전체생존기간 차이는 통계적으로 유의하지 않았습니다(34.9개월 대 28.0개월, 위험비 0.81, 95% 신뢰구간 0.64–1.03). 주요 위해는 3–4등급 호중구감소증으로 62.0% 대 0.6%에서 발생했으며, 발열성 호중구감소증은 두 군 모두 0.6%, 이상반응으로 인한 치료 중단은 2.6% 대 1.7%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ORIENT16", "trial": "G-ORIENT16", "papers": [ { "key": "P-ORIENT16", "pmid": "38051328", "title": "Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.", "journal": "JAMA", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/38051328/", "doi": "10.1001/jama.2023.19918", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-PDL1" ], "limits": "All patients were enrolled in China; the abstract does not report results for patients with a low PD-L1 score separately, so the all-patient result does not show benefit in that group. HER2 status and later-line treatments are not described in the abstract. Results for sintilimab are not evidence about other PD-1 antibodies, and no cross-trial comparison is made.", "label": "ORIENT-16 · first-line sintilimab plus chemotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, with capecitabine and oxaliplatin", "population": "Unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, enrolled in China", "claim": "In this double-blind, placebo-controlled phase 3 trial at 62 hospitals in China, 650 patients were randomised to sintilimab (n = 327) or placebo (n = 323), each with capecitabine and oxaliplatin; 397 (61.1%) had a PD-L1 combined positive score of 5 or more. In all randomised patients, median overall survival was 15.2 versus 12.3 months (stratified hazard ratio 0.77, 95% CI 0.63-0.94; P = .009). In patients with a score of 5 or more, it was 18.4 versus 12.9 months (hazard ratio 0.66, 95% CI 0.50-0.86; P = .002). Grade 3 or higher treatment-related decreased platelet count occurred in 24.7% versus 21.3% and anaemia in 12.5% versus 8.8%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "G-ORIENT16", "nct": "NCT03745170", "acronym": null, "title": "Efficacy and Safety Evaluation of Sintilimab or Placebo in Combination With XELOX as First Line Treatment in Patients With Gastric Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 650, "sponsor": "Innovent Biologics (Suzhou) Co. Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2018-12-19", "lastUpdate": "2023-03-01", "url": "https://clinicaltrials.gov/study/NCT03745170" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival time from randomization", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 650, "assessment": "not stated", "quote": "Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020." }, "effect": { "measure": "HR", "value": 0.77, "ci_low": 0.63, "ci_high": 0.94, "ci_level": "95%", "p": ".009", "endpoint": "Overall survival, all randomized patients", "quote": "Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%)." }, "takeaway_en": "In patients in China with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, adding sintilimab to first-line capecitabine plus oxaliplatin lengthened median overall survival from 12.3 to 15.2 months compared with placebo (hazard ratio 0.77). In patients with a PD-L1 CPS of 5 or more, the hazard ratio was 0.66 (18.4 vs 12.9 months), and grade 3 or higher treatment-related decreased platelet count (24.7% vs 21.3%) and anemia (12.5% vs 8.8%) were somewhat more frequent with sintilimab.", "takeaway_ko": "중국에서 등록된 절제 불가능한 국소진행성 또는 전이성 위암 및 위식도접합부 선암 환자를 대상으로 했습니다. 1차 카페시타빈·옥살리플라틴 요법에 신틸리맙을 추가하자 위약 대비 전체생존기간 중앙값이 12.3개월에서 15.2개월로 연장되었습니다(위험비 0.77). PD-L1 CPS 5 이상 환자에서는 위험비가 0.66(18.4개월 대 12.9개월)이었으며, 3등급 이상 치료 관련 혈소판 감소(24.7% 대 21.3%)와 빈혈(12.5% 대 8.8%)은 신틸리맙군에서 다소 더 많았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ARMANI", "trial": "G-ARMANI", "papers": [ { "key": "P-ARMANI24", "pmid": "39557058", "title": "Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line oxaliplatin-based chemotherapy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer (ARMANI): a randomised, open-label, multicentre, phase 3 trial.", "journal": "Lancet Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39557058/", "doi": "10.1016/S1470-2045(24)00580-1", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [ "G-HER2NEG" ], "limits": "The primary end point was progression-free survival in an open-label trial; overall survival is not reported in this abstract. Patients had not received first-line immunotherapy, which has since become common, so the result may not apply after chemo-immunotherapy. Only patients with disease control after 3 months were eligible. All participants were White and enrolled in Italy.", "label": "ARMANI · switch maintenance with ramucirumab plus paclitaxel", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "After disease control on 3 months of first-line oxaliplatin-based chemotherapy", "population": "Locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer", "claim": "In the open-label phase 3 ARMANI trial at 31 hospitals in Italy, 280 patients were randomised to switch to paclitaxel plus ramucirumab (n=144) or to continue oxaliplatin-based chemotherapy followed by fluoropyrimidine maintenance (n=136). At a median follow-up of 43.7 months, median progression-free survival was 6.6 versus 3.5 months (HR 0.61, 95% CI 0.48-0.79; p=0.0002). The proportional hazards assumption was violated; 24-month restricted mean progression-free survival was 8.8 versus 6.1 months (p=0.0010). Grade 3-4 treatment-related neutropenia occurred in 26% versus 10%, and serious adverse events in 20% versus 11%.", "by": "Claude", "added": "2026-10-06", "trialRecord": { "key": "G-ARMANI", "nct": "NCT02934464", "acronym": "ARMANI", "title": "Assessment of Ramucirumab Plus Paclitaxel as Switch MANteInance Versus Continuation of First-line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 280, "sponsor": "Fondazione IRCCS Istituto Nazionale dei Tumori, Milano", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2016-12", "lastUpdate": "2021-09-13", "url": "https://clinicaltrials.gov/study/NCT02934464" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (intention-to-treat)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 280, "assessment": "not stated", "quote": "ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. … 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136)." }, "effect": { "measure": "HR", "value": 0.61, "ci_low": 0.48, "ci_high": 0.79, "ci_level": "95%", "p": "p=0·0002", "endpoint": "Progression-free survival", "quote": "Median progression-free survival was 6·6 months (95% CI 5·9-7·8) in the switch maintenance group and 3·5 months (2·8-4·2) in the control group (HR 0·61, 95% CI 0·48-0·79; p=0·0002). The assumption of proportional hazards was violated" }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "None", "quote": "The most frequent grade 3-4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group … No treatment-related deaths occurred." }, "takeaway_en": "In 280 patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who had disease control after 3 months of FOLFOX or CAPOX, switching to paclitaxel plus ramucirumab improved progression-free survival compared with continuing oxaliplatin-based chemotherapy and then fluoropyrimidine maintenance (median 6.6 vs 3.5 months; HR 0.61, 95% CI 0.48-0.79), although the proportional hazards assumption was violated. The switch strategy caused more grade 3-4 neutropenia (26% vs 10%) and more serious adverse events (20% vs 11%), and no treatment-related deaths occurred.", "takeaway_ko": "FOLFOX 또는 CAPOX 3개월 투여 후 질병 조절이 확인된 진행성 HER2 음성 위암 또는 위식도접합부암 환자 280명을 대상으로 했습니다. 파클리탁셀+라무시루맙으로 전환한 군은 옥살리플라틴 기반 항암화학요법을 지속한 뒤 플루오로피리미딘 유지요법을 받은 군보다 무진행생존기간이 개선되었습니다(중앙값 6.6개월 대 3.5개월; HR 0.61, 95% CI 0.48-0.79). 다만 비례위험 가정은 충족되지 않았습니다. 전환군에서 3-4등급 호중구감소증(26% 대 10%)과 중대한 이상반응(20% 대 11%)이 더 많았으며, 치료 관련 사망은 없었습니다.", "certainty": { "level": "low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CCNE1Lee15", "trial": null, "papers": [ { "key": "P-CCNE1Lee15", "pmid": "25786580", "title": "The impact of concomitant genomic alterations on treatment outcome for trastuzumab therapy in HER2-positive gastric cancer.", "journal": "Sci Rep", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25786580/", "doi": "10.1038/srep09289", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "Single centre, 50 patients, no untreated or trastuzumab-free comparison group, so a prognostic effect of CCNE1 cannot be separated from an effect on trastuzumab benefit. The abstract gives no effect size or count for the CCNE1 finding and several alterations were tested. The abstract's own overall conclusion is that prediction remained unclear.", "program": "gastric", "label": "Concomitant alterations and trastuzumab outcome · one Korean centre", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Trastuzumab with chemotherapy for advanced disease", "population": "50 HER2-positive advanced gastric cancer patients at one centre", "claim": "Among 50 patients treated with trastuzumab plus chemotherapy, at least one concomitant alteration was found in 40% by immunohistochemistry, 16% by copy number and 64% by panel sequencing. Median progression-free survival was 8.0 months (95% CI 4.8-11.3). Concomitant alterations as a group did not correlate with trastuzumab response when patients were divided at a progression-free survival of 8 months; CCNE1 copy number gain correlated with shorter survival (p < 0.05).", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CyclinEScaltriti11", "trial": null, "papers": [ { "key": "P-CyclinEScaltriti11", "pmid": "21321214", "title": "Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients.", "journal": "Proc Natl Acad Sci U S A", "year": "2011", "url": "https://pubmed.ncbi.nlm.nih.gov/21321214/", "doi": "10.1073/pnas.1014835108", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "B-HER2POS" ], "limits": "The patient cohort has 34 people and no trastuzumab-free comparison, so the clinical association cannot separate prognosis from prediction. The causal evidence comes from cell lines and xenografts. Amplification and overexpression are combined into one category. Breast cancer models are not evidence about gastric cancer. One author was employed by a company developing a CDK inhibitor.", "program": "breast", "label": "Cyclin E and trastuzumab resistance · cell models and 34 patients", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Trastuzumab-resistant cell lines, xenografts and a small treated cohort", "population": "HER2-amplified breast cancer cell models; 34 HER2-positive patients treated with trastuzumab-based therapy", "claim": "Cells made resistant by chronic trastuzumab exposure acquired a focal amplification containing the cyclin E gene. In 34 patients given trastuzumab-based therapy, cyclin E amplification or overexpression was associated with a lower clinical benefit rate (33.3% compared with 87.5%, P < 0.02) and shorter progression-free survival (6 months versus 14 months, P < 0.002). Cyclin E overexpression produced resistance in vitro and in vivo, and CDK2 inhibition reduced growth of trastuzumab-resistant xenografts.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AMNESIA18", "trial": null, "papers": [ { "key": "P-AMNESIA18", "pmid": "29208673", "title": "Biomarkers of Primary Resistance to Trastuzumab in HER2-Positive Metastatic Gastric Cancer Patients: the AMNESIA Case-Control Study.", "journal": "Clin Cancer Res", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29208673/", "doi": "10.1158/1078-0432.CCR-17-2781", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "Cases and controls were chosen by their response, which inflates apparent accuracy compared with an unselected population. Thirty-seven patients; no trastuzumab-free group. The panel does not include CCNE1, so this study says nothing about cyclin E. A later analysis in a randomised trial did not confirm an independent effect of the panel.", "program": "gastric", "label": "AMNESIA · candidate alterations and primary trastuzumab resistance", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Trastuzumab-based therapy for metastatic disease; resistant cases versus sensitive controls", "population": "HER2-positive metastatic gastric cancer; 37 patients in a multicentre case-control study", "claim": "In this prospective case-control study, alterations from a prespecified panel of EGFR, MET, KRAS, PI3K and PTEN mutations and EGFR, MET and KRAS amplifications were found in 11 of 20 resistant patients (55%) and none of 17 sensitive patients (P < 0.001), and in 7 of 13 (53.8%) HER2 2+ tumours versus 4 of 24 (16.7%) 3+ tumours. Patients without a panel alteration had longer median progression-free survival (5.2 vs. 2.6 months; HR 0.34, 95% CI 0.07-0.48) and overall survival (16.1 vs. 7.6 months; HR 0.38, 95% CI 0.09-0.75). Predictive accuracy was 76% for the panel, 65% for HER2 immunohistochemistry and 84% for both combined.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CCNE1Rustgi24", "trial": null, "papers": [ { "key": "P-CCNE1Rustgi24", "pmid": "38717153", "title": "Molecular Landscape and Clinical Implication of CCNE1-amplified Esophagogastric Cancer.", "journal": "Cancer Res Commun", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38717153/", "doi": "10.1158/2767-9764.CRC-23-0496", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "The abstract gives no hazard ratio, patient count or adjustment for the survival findings. Real-world survival from insurance claims is not a trial end point, and treated patients were not randomised. Tumours sent for commercial profiling are a selected population. Several authors are employees of the laboratory.", "program": "gastric", "label": "CCNE1-amplified esophagogastric cancer · commercial profiling database", "kind": "genomics", "level": "clinical", "result": "descriptive", "setting": "Tumour profiling with linked real-world survival", "population": "7,083 esophagogastric tumours profiled by one commercial laboratory", "claim": "Among 7,083 esophagogastric tumours, CCNE1 amplification was found in 6.2% of esophageal adenocarcinoma, 7.0% of esophagogastric junction carcinoma, 4.2% of gastric adenocarcinoma and 0.8% of esophageal squamous cell carcinoma, and was more frequent in lymph node and liver metastases than in primary tumours. It was associated with more frequent TP53 mutation and ERBB2 amplification and less frequent CDH1 mutation. In real-world survival analysis, patients with CCNE1-amplified gastric cancer had worse survival after trastuzumab for HER2-positive tumours and better survival after immunotherapy.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CCNE1TDXd24", "trial": null, "papers": [ { "key": "P-CCNE1TDXd24", "pmid": "38748981", "title": "Impact of Genomic Alterations on Efficacy of Trastuzumab Deruxtecan Against Human Epidermal Growth Factor Receptor-2-Positive Advanced Gastric Cancer.", "journal": "JCO Precis Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38748981/", "doi": "10.1200/PO.23.00681", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "Retrospective registry analysis without a comparison treatment, so CCNE1 could mark worse prognosis rather than less benefit from the drug. The lower confidence bound is close to 1 and several genes were examined. Patients who undergo genomic profiling in later lines are selected. Response rates by CCNE1 status are not given in the abstract.", "program": "gastric", "label": "CCNE1 amplification and trastuzumab deruxtecan · Japanese national database", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Trastuzumab deruxtecan for advanced disease, with comprehensive genomic profiling", "population": "114 HER2-positive advanced gastric or gastroesophageal junction cancer patients in a nationwide Japanese database", "claim": "Among 114 patients, the most frequently altered genes were TP53 (82%), ERBB2 (80%) and CCNE1 (36%). In 91 patients profiled before treatment, CCNE1 amplification predicted shorter progression-free survival after trastuzumab deruxtecan in multivariate analysis (median 131 days v 189 days; HR 1.90, 95% CI 1.02 to 3.53; P = .044). Across 1,450 tumours, CCNE1 amplification was found in 41% of ERBB2-amplified tumours versus 11% of ERBB2-nonamplified tumours. ERBB2-activating mutations were found in 8.8% of treated HER2-positive tumours and were associated with shorter progression-free survival (105 v 180 days; P = .046).", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2GCKwon23", "trial": null, "papers": [ { "key": "P-HER2GCKwon23", "pmid": "36916290", "title": "Genetic and immune microenvironment characterization of HER2-positive gastric cancer: Their association with response to trastuzumab-based treatment.", "journal": "Cancer Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36916290/", "doi": "10.1002/cam4.5769", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "This points the opposite way from reports linking CCNE1 amplification to worse outcome, and the abstract gives no effect size or count for it. Sequencing was done in 21 selected cases and the rest relied on in situ hybridisation and immunohistochemistry. Many markers were tested without stated correction. Single centre, no trastuzumab-free comparison.", "program": "gastric", "label": "Cell-cycle alterations and first-line trastuzumab · opposite direction", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "First-line trastuzumab-based treatment", "population": "HER2-positive advanced gastric adenocarcinoma at one Korean centre; 21 cases sequenced, findings checked in the whole cohort", "claim": "Patients who progressed before 6 months had more frequent EGFR, HER3 and MET amplification, whereas the others had more frequent amplification of G1/S cell-cycle checkpoint genes. In the whole cohort, CCNE1 amplification, cyclin A and PLK1 overexpression and lower cyclin D3 and HER3 expression were significant predictors of better progression-free survival (p < 0.05), as were a high density of CD3-negative CD57-positive NK cells and a PD-L1 combined positive score ≥5.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-OncogeneDominance26", "trial": null, "papers": [ { "key": "P-OncogeneDominance26", "pmid": "41832911", "title": "Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.", "journal": "Target Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41832911/", "doi": "10.1007/s11523-026-01204-5", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "Thirty-two patients; the dominance definition was not stated to be prespecified and the hazard ratios are unstable at this size. The abstract does not separate CCNE1 from the other co-amplified genes. No trastuzumab-free comparison. Individual data are not public.", "program": "gastric", "label": "ERBB2 copy-number dominance among co-amplified oncogenes", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "First-line trastuzumab with S-1 and oxaliplatin; sequencing study attached to a trial", "population": "32 HER2-positive gastric cancer patients in Japan", "claim": "Among 32 patients, ERBB2 amplification was present in 84.4%, and 75% had ERBB2 co-amplified with other oncogenes including KRAS, MET, FGFR2 and CCNE1. Tumours in which another oncogene had a higher copy number than ERBB2 had shorter progression-free survival (median 6.9 vs 17.0 months, hazard ratio 6.40, p = 0.001) and overall survival (14.8 vs 35.5 months, hazard ratio 2.72, p = 0.016) and a numerically lower response rate (63.6% vs 90.0%, p = 0.151).", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CyclinELuhtala16", "trial": null, "papers": [ { "key": "P-CyclinELuhtala16", "pmid": "26810187", "title": "Cyclin E amplification, over-expression, and relapse-free survival in HER-2-positive primary breast cancer.", "journal": "Tumour Biol", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/26810187/", "doi": "10.1007/s13277-016-4870-z", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "B-HER2POS" ], "limits": "With amplification in 8% of 202 tumours the number of amplified cases is small, so a moderate effect cannot be excluded. Trastuzumab was given for 9 weeks, shorter than standard treatment. Early-stage relapse-free survival is a different question from response in metastatic disease. Amplification was assessed by in situ hybridisation with its own threshold.", "program": "breast", "label": "Cyclin E in HER2-positive primary breast cancer · no survival association", "kind": "observational", "level": "clinical", "result": "negative", "setting": "Primary tumours, with or without short adjuvant trastuzumab", "population": "202 HER2-positive primary breast carcinomas", "claim": "In 202 HER2-positive primary breast carcinomas, cyclin E was highly expressed in 37% and CCNE1 was amplified in 8%. Neither high cyclin E expression nor CCNE1 amplification was associated with relapse-free survival, irrespective of a 9-week adjuvant trastuzumab regimen.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-SecondaryEventsKim14", "trial": null, "papers": [ { "key": "P-SecondaryEventsKim14", "pmid": "25401468", "title": "Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma.", "journal": "J Clin Invest", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25401468/", "doi": "10.1172/JCI75200", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "subtypes": [ "G-HER2" ], "limits": "The resistance evidence comes from cell lines; the abstract reports no patient outcome by alteration and no frequencies. Cell-line drug sensitivity does not establish benefit from combination therapy in patients.", "program": "gastric", "label": "Secondary oncogenic events in ERBB2-amplified gastroesophageal cancer", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Genomic profiles and cell-line experiments", "population": "ERBB2-amplified gastroesophageal adenocarcinoma tumours and cell lines", "claim": "Most ERBB2-amplified gastroesophageal adenocarcinomas carried secondary oncogenic alterations in cell-cycle regulation, PI3K signalling or receptor tyrosine kinase genes. In ERBB2-amplified cell lines, such secondary events conferred resistance to ERBB2-directed therapy, which was overcome by also targeting the secondary oncogene. EGFR was commonly co-amplified with ERBB2.", "by": "Claude", "added": "2026-10-06", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CM577", "trial": "G-CM577", "papers": [ { "key": "P-CM577", "pmid": "33789008", "title": "Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.", "journal": "N Engl J Med", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33789008/", "doi": "10.1056/NEJMoa2032125", "errata": [ { "pmid": "36791183", "title": "Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.", "url": "https://pubmed.ncbi.nlm.nih.gov/36791183/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "The trial enrolled esophageal and gastroesophageal junction cancer after chemoradiotherapy, not gastric cancer treated with perioperative chemotherapy, so it does not answer the question for stomach tumours. The abstract reports disease-free survival, not overall survival. A published correction changed the baseline counts by tumour location; this unit does not use them.", "label": "CheckMate 577 · adjuvant nivolumab after chemoradiotherapy and surgery", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Adjuvant, after neoadjuvant chemoradiotherapy and resection with residual pathological disease", "population": "Resected esophageal or gastroesophageal junction cancer", "claim": "In the placebo-controlled phase 3 CheckMate 577 trial, 532 patients received nivolumab and 262 received placebo. At a median follow-up of 24.4 months, median disease-free survival was 22.4 months (95% CI 16.6 to 34.0) versus 11.0 months (95% CI 8.3 to 14.3) (hazard ratio for recurrence or death 0.69; 96.4% CI 0.56 to 0.86; P<0.001). Grade 3 or 4 treatment-related adverse events occurred in 71 of 532 patients (13%) versus 15 of 260 (6%), and treatment was discontinued for related adverse events in 9% versus 3%.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "G-CM577", "nct": "NCT02743494", "acronym": "CheckMate 577", "title": "An Investigational Immuno-therapy Study of Nivolumab or Placebo in Participants With Resected Esophageal or Gastroesophageal Junction Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 794, "sponsor": "Bristol-Myers Squibb", "sponsorClass": "INDUSTRY", "collaborators": [ "Ono Pharmaceutical Co., Ltd." ], "hasResults": true, "start": "2016-07-14", "lastUpdate": "2025-11-18", "url": "https://clinicaltrials.gov/study/NCT02743494" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Disease-free survival", "primary_endpoint_type": "DFS/iDFS/EFS/RFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": null, "assessment": "not stated", "quote": "We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial … were randomly assigned in a 2:1 ratio to receive nivolumab … or matching placebo.", "quote_note": "Abstract gives arm sizes (532 nivolumab, 262 placebo) but no stated total randomized; it does not specify who assessed disease-free survival." }, "effect": { "measure": "HR", "value": 0.69, "ci_low": 0.56, "ci_high": 0.86, "ci_level": "96.4%", "p": "P<0.001", "endpoint": "Disease-free survival (disease recurrence or death)", "quote": "the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 13, "grade3plus_control_pct": 6, "discontinuation_experimental_pct": 9, "discontinuation_control_pct": 3, "treatment_related_deaths": null, "quote": "Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.", "quote_note": "Figures are treatment-related grade 3 or 4 events, not all-cause grade ≥3; treatment-related deaths not reported in abstract." }, "takeaway_en": "In adults with resected stage II or III esophageal or gastroesophageal junction cancer who had residual pathological disease after neoadjuvant chemoradiotherapy, up to 1 year of adjuvant nivolumab lengthened median disease-free survival to 22.4 months versus 11.0 months with placebo (hazard ratio 0.69; 96.4% CI 0.56 to 0.86) at a median follow-up of 24.4 months. Treatment-related grade 3 or 4 adverse events occurred in 13% versus 6% of patients, and related discontinuation in 9% versus 3%.", "takeaway_ko": "선행 항암화학방사선요법 후 근치적 절제(R0)를 받았으나 병리학적 잔존 병변이 남은 2기 또는 3기 식도암 또는 위식도접합부암 성인에서, 최대 1년간의 니볼루맙 보조요법은 위약 대비 무병생존기간 중앙값을 22.4개월 대 11.0개월로 연장하였습니다(위험비 0.69, 96.4% 신뢰구간 0.56–0.86, 추적관찰 기간 중앙값 24.4개월). 치료 관련 3–4등급 이상반응은 13% 대 6%에서 발생했으며, 치료 관련 이상반응으로 인한 투약 중단은 9% 대 3%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-DANTE", "trial": "G-DANTE", "papers": [ { "key": "P-DANTE24", "pmid": "37963317", "title": "Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/37963317/", "doi": "10.1200/JCO.23.00975", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [ "BM-PDL1-CPS", "BM-MSI" ], "subtypes": [ "G-PDL1", "G-MSI" ], "limits": "Interim, exploratory pathology end points from a phase II part; survival is not reported and the authors describe the data as exploratory. The subgroup differences rest on small numbers (23 microsatellite-unstable tumours across both arms). Pathological regression is not a survival benefit.", "label": "DANTE · perioperative atezolizumab plus FLOT, interim", "program": "gastric", "kind": "rct", "level": "clinical", "result": "descriptive", "setting": "Perioperative chemotherapy with or without atezolizumab", "population": "Resectable esophagogastric adenocarcinoma", "claim": "In the randomised phase II part, patients were assigned to FLOT plus atezolizumab (146) or FLOT alone (149). Histopathological complete regression was more frequent with atezolizumab (24% versus 15%; one-sided P = .032), with a larger difference in tumours with PD-L1 combined positive score ≥10 (33% versus 12%) and with microsatellite instability (63% versus 27%). Twenty-three patients (8%) had microsatellite-unstable tumours. Surgical morbidity (45% versus 42%), 60-day mortality (3% versus 2%) and complete resection (96% versus 95%) were similar.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "G-DANTE", "nct": "NCT03421288", "acronym": "DANTE", "title": "Study of Atezolizumab + FLOT vs. FLOT Alone in Patients With GC/GEJ and High Immune Responsiveness", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 677, "sponsor": "Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest", "sponsorClass": "OTHER", "collaborators": [ "Roche Pharma AG" ], "hasResults": false, "start": "2018-09-14", "lastUpdate": "2025-07-25", "url": "https://clinicaltrials.gov/study/NCT03421288" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-PETRARCA", "trial": "G-PETRARCA", "papers": [ { "key": "P-PETRARCA22", "pmid": "35709415", "title": "FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2-Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35709415/", "doi": "10.1200/JCO.22.00380", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "Eighty-one patients; the trial stopped early after a negative trial of pertuzumab in metastatic disease, so the survival comparisons are underpowered and not significant. A higher pathological response did not translate into an established survival benefit. Toxicity was clearly higher.", "label": "PETRARCA · perioperative trastuzumab and pertuzumab with FLOT", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Perioperative chemotherapy with or without dual HER2 antibodies", "population": "HER2-positive resectable esophagogastric adenocarcinoma", "claim": "The trial closed early without moving to phase III. Eighty-one patients had been assigned to FLOT alone (41) or FLOT with trastuzumab and pertuzumab (40). The pathological complete response rate was 12% versus 35% (P = .02) and node-negative pathology 39% versus 68%. Median disease-free survival was 26 months versus not reached (hazard ratio 0.58; P = .14), and overall survival at a median follow-up of 22 months showed a hazard ratio of 0.56 (P = .24). Grade 3 or higher diarrhoea occurred in 5% versus 41% and leukopenia in 13% versus 23%.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "G-PETRARCA", "nct": "NCT02581462", "acronym": "PETRARCA", "title": "FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of HER-2 Expressing Gastric or GEJ Cancer", "status": "COMPLETED", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 81, "sponsor": "Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest", "sponsorClass": "OTHER", "collaborators": [ "Trium Analysis Online GmbH" ], "hasResults": false, "start": "2016-06", "lastUpdate": "2020-08-11", "url": "https://clinicaltrials.gov/study/NCT02581462" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-COMPASSION15", "trial": "G-COMPASSION15", "papers": [ { "key": "P-COMPASSION15", "pmid": "39843940", "title": "First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39843940/", "doi": "10.1038/s41591-024-03450-4", "errata": [ { "pmid": "40140623", "title": "Author Correction: First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.", "url": "https://pubmed.ncbi.nlm.nih.gov/40140623/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-HER2NEG", "G-PDL1" ], "limits": "Interim analysis; all centres were in China. The abstract does not give the result for patients with a low PD-L1 score, so the all-patient result does not by itself show benefit in that group. The comparison is with chemotherapy alone, not with a PD-1 antibody plus chemotherapy. A published author correction fixed figure labels and one hazard ratio in a figure; the abstract values used here were not changed.", "label": "COMPASSION-15 · first-line cadonilimab plus chemotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, with chemotherapy", "population": "Untreated, unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma", "claim": "In this double-blind phase 3 trial, 610 patients from 75 centres were randomised to the PD-1/CTLA-4 bispecific antibody cadonilimab (n = 305) or placebo (n = 305), each with chemotherapy. At the prespecified interim analysis with a median follow-up of 18.7 months, median overall survival was 14.1 versus 11.1 months (HR 0.66; 95% CI 0.54-0.81; P < 0.001); the primary end point was met. Median progression-free survival was 7.0 versus 5.3 months (HR 0.53, 95% CI 0.44-0.65). In patients with a PD-L1 combined positive score ≥5, median overall survival was 15.3 versus 10.9 months (HR 0.58, 95% CI 0.41-0.82). Grade ≥3 treatment-related adverse events occurred in 65.9% versus 53.6%.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "G-COMPASSION15", "nct": "NCT05008783", "acronym": null, "title": "A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 610, "sponsor": "Akeso", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2021-09-17", "lastUpdate": "2025-11-19", "url": "https://clinicaltrials.gov/study/NCT05008783" }, "sources": 2, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival (OS) in the intention-to-treat population", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 610, "assessment": "not stated", "quote": "This was a randomized, double-blind, placebo-controlled phase 3 study. … As of 18 August 2023, 610 patients from 75 study centers were randomized to cadonilimab (n = 305) or placebo (n = 305)." }, "effect": { "measure": "HR", "value": 0.66, "ci_low": 0.54, "ci_high": 0.81, "ci_level": "95%", "p": "P < 0.001", "endpoint": "Overall survival (intention-to-treat)", "quote": "With a median follow-up of 18.7 months, the cadonilimab group had a significantly longer median OS (14.1 versus 11.1 months; hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.54-0.81; P < 0.001) than the placebo group." }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "Prespecified interim analysis (median follow-up 18.7 months)", "experimental_pct": 65.2, "control_pct": 48.9, "higher_is_better": true, "experimental_arm": "Cadonilimab plus chemotherapy", "control_arm": "Placebo plus chemotherapy", "quote": "The objective response rate was 65.2% versus 48.9% with a median duration of response of 8.8 months versus 4.4 months.", "difference_pp": 16.3, "nnt": 7, "quote_note": "Single paper, prespecified interim analysis" } ], "harms": { "grade3plus_experimental_pct": 65.9, "grade3plus_control_pct": 53.6, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade ≥3 treatment-related adverse events occurred in 65.9% of the cadonilimab group and 53.6% of the placebo group, and the most common were decreased platelet count, decreased neutrophil count and anemia. Most of the immune-related adverse events were grade 1 or 2." }, "takeaway_en": "In untreated, unresectable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma, adding the PD-1/CTLA-4 bispecific antibody cadonilimab to first-line chemotherapy instead of placebo raised the objective response rate from 48.9% to 65.2%, and median overall survival was 14.1 versus 11.1 months (HR 0.66). The trade-off was more grade ≥3 treatment-related adverse events (65.9% vs 53.6%), mainly decreased platelet count, decreased neutrophil count and anemia, while most immune-related adverse events were grade 1 or 2.", "takeaway_ko": "치료받지 않은 절제 불가능한 국소진행성 또는 전이성 HER2 음성 위 또는 위식도접합부 선암 환자에서 1차 항암화학요법에 위약 대신 PD-1/CTLA-4 이중특이항체 카도닐리맙을 추가했습니다. 그 결과 객관적 반응률이 48.9%에서 65.2%로 높아졌고, 중앙 전체생존기간은 14.1개월 대 11.1개월이었습니다(위험비 0.66). 대신 3등급 이상 치료 관련 이상반응이 더 많았으며(65.9% 대 53.6%), 주로 혈소판 감소, 호중구 감소, 빈혈이었습니다. 면역 관련 이상반응은 대부분 1–2등급이었습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KN756", "trial": "B-KN756", "papers": [ { "key": "P-KN756", "pmid": "39838117", "title": "Pembrolizumab and chemotherapy in high-risk, early-stage, ER(+)/HER2(-) breast cancer: a randomized phase 3 trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39838117/", "doi": "10.1038/s41591-024-03415-7", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Only one of two dual primary end points has been reported; event-free survival is immature, so a recurrence or survival benefit is not established. Pathological complete response is uncommon and less clearly linked to long-term outcome in ER-positive disease than in other subtypes. Results by PD-L1 status are not in this abstract.", "label": "KEYNOTE-756 · neoadjuvant pembrolizumab in ER-positive early breast cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Neoadjuvant chemotherapy with pembrolizumab or placebo, then adjuvant pembrolizumab or placebo with endocrine therapy", "population": "Previously untreated, grade 3, high-risk ER-positive, HER2-negative early breast cancer", "claim": "In the double-blind phase 3 KEYNOTE-756 trial, 635 patients were assigned to pembrolizumab plus chemotherapy and 643 to placebo plus chemotherapy. At the first interim analysis, the pathological complete response rate was 24.3% (95% CI 21.0-27.8%) versus 15.6% (95% CI 12.8-18.6%) (estimated difference 8.5 percentage points; 95% CI 4.2-12.8; P = 0.00005). Event-free survival, the other dual primary end point, was not mature. Grade ≥3 treatment-related adverse events in the neoadjuvant phase occurred in 52.5% versus 46.4%.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-KN756", "nct": "NCT03725059", "acronym": null, "title": "Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 1240, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2018-12-27", "lastUpdate": "2025-07-11", "url": "https://clinicaltrials.gov/study/NCT03725059" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Dual primary endpoints: pathological complete response and event-free survival in the intention-to-treat population (only pCR reported; EFS not mature)", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": null, "assessment": "not stated", "quote": "We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER+/HER2- grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) … In total, 635 patients were assigned to the pembrolizumab-chemotherapy arm and 643 to the placebo-chemotherapy arm." }, "effect": { "measure": "difference", "value": 8.5, "ci_low": 4.2, "ci_high": 12.8, "ci_level": "95%", "p": "0.00005", "endpoint": "Pathological complete response rate (first interim analysis)", "quote": "estimated treatment difference, 8.5 percentage points; 95% CI, 4.2-12.8; P = 0.00005" }, "landmark": [ { "endpoint": "Pathological complete response rate", "timepoint": "At surgery after neoadjuvant therapy (prespecified first interim analysis)", "experimental_pct": 24.3, "control_pct": 15.6, "higher_is_better": true, "experimental_arm": "Pembrolizumab plus chemotherapy", "control_arm": "Placebo plus chemotherapy", "quote": "At the study's prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0-27.8%) in the pembrolizumab-chemotherapy arm and 15.6% (95% CI, 12.8-18.6%) in the placebo-chemotherapy arm", "difference_pp": 8.7, "nnt": 12, "quote_note": "P-KN756, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": 52.5, "grade3plus_control_pct": 46.4, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab-chemotherapy and placebo-chemotherapy arms, respectively." }, "takeaway_en": "In patients with previously untreated, grade 3, high-risk ER-positive, HER2-negative early breast cancer, adding pembrolizumab to neoadjuvant chemotherapy raised the pathological complete response rate from 15.6% to 24.3% (difference 8.5 percentage points), while event-free survival was not yet mature. Grade ≥3 treatment-related adverse events during the neoadjuvant phase occurred in 52.5% with pembrolizumab versus 46.4% with placebo.", "takeaway_ko": "이전에 치료받지 않은 3등급 고위험 ER 양성, HER2 음성 조기 유방암 환자에서 선행항암화학요법에 펨브롤리주맙을 추가하자 병리학적 완전관해율이 15.6%에서 24.3%로 높아졌습니다(차이 8.5%p). 무사건생존 자료는 아직 성숙하지 않았습니다. 선행요법 기간 중 3등급 이상 치료 관련 이상반응은 펨브롤리주맙군 52.5%, 위약군 46.4%에서 발생했습니다.", "certainty": { "level": "moderate", "reasons": [ "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CM7FL", "trial": "B-CM7FL", "papers": [ { "key": "P-CM7FL", "pmid": "39838118", "title": "Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.", "journal": "Nat Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39838118/", "doi": "10.1038/s41591-024-03414-8", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-HR", "BM-PDL1-B" ], "subtypes": [ "B-HRPOS" ], "limits": "The end point is pathological response; no recurrence or survival result is reported in this abstract. Two treatment-related deaths occurred in a curable population. The PD-L1 result is a subgroup. The independent trial of pembrolizumab in a similar population has also reported pathological response only.", "label": "CheckMate 7FL · neoadjuvant nivolumab in ER-positive early breast cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Neoadjuvant anthracycline and taxane chemotherapy with nivolumab or placebo", "population": "Newly diagnosed high-risk ER-positive, HER2-negative primary breast cancer", "claim": "In the double-blind phase 3 CheckMate 7FL trial, 510 patients were randomised. The primary end point, pathological complete response, was 24.5% with nivolumab versus 13.8% with placebo (P = 0.0021), with a larger difference in PD-L1-positive tumours (44.3% versus 20.2%). Five deaths occurred in the nivolumab arm, two related to study drug toxicity; no deaths occurred in the placebo arm.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-CM7FL", "nct": "NCT04109066", "acronym": "CheckMate 7FL", "title": "Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Participants With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 521, "sponsor": "Bristol-Myers Squibb", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2019-11-18", "lastUpdate": "2025-01-08", "url": "https://clinicaltrials.gov/study/NCT04109066" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathological complete response (pCR)", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 510, "assessment": "not stated", "quote": "We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2- primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": "0.0021", "endpoint": "pCR", "quote": "The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021)" }, "landmark": [ { "endpoint": "pCR (all randomized patients)", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 24.5, "control_pct": 13.8, "higher_is_better": true, "experimental_arm": "Nivolumab + anthracycline/taxane chemotherapy", "control_arm": "Placebo + anthracycline/taxane chemotherapy", "quote": "The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021)", "difference_pp": 10.7, "nnt": 10, "quote_note": "P-CM7FL (Nat Med 2025), the only paper provided" }, { "endpoint": "pCR (PD-L1-positive tumors, VENTANA SP142 ≥1%)", "timepoint": "at surgery after neoadjuvant therapy", "experimental_pct": 44.3, "control_pct": 20.2, "higher_is_better": true, "experimental_arm": "Nivolumab + anthracycline/taxane chemotherapy", "control_arm": "Placebo + anthracycline/taxane chemotherapy", "quote": "with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively)", "difference_pp": 24.1, "nnt": 5, "quote_note": "P-CM7FL (Nat Med 2025), the only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Five deaths occurred in the nivolumab arm, two of them related to study drug toxicity. No deaths occurred in the placebo arm.", "quote": "There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm." }, "takeaway_en": "In 510 patients with newly diagnosed high-risk ER-positive, HER2-negative early breast cancer, adding nivolumab to neoadjuvant anthracycline and taxane chemotherapy raised the pCR rate from 13.8% to 24.5% (P = 0.0021), and from 20.2% to 44.3% in PD-L1-positive tumors. No new safety signals were identified, but two deaths in the nivolumab arm were related to study drug toxicity, versus no deaths in the placebo arm; long-term survival outcomes are not reported in this abstract.", "takeaway_ko": "새로 진단된 고위험 ER 양성, HER2 음성 조기 유방암 환자 510명에서 안트라사이클린·탁산 기반 수술 전 보조항암화학요법에 니볼루맙을 추가하자 병리학적 완전관해(pCR)율이 13.8%에서 24.5%로 높아졌고(P = 0.0021), PD-L1 양성 종양에서는 20.2%에서 44.3%로 높아졌습니다. 새로운 안전성 신호는 확인되지 않았습니다. 다만 니볼루맙군에서 연구 약물 독성과 관련된 사망이 2건 있었고 위약군에서는 사망이 없었으며, 장기 생존 결과는 이 초록에 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "no confidence interval for the primary effect in the abstract", "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-KRISTINE", "trial": "B-KRISTINE", "papers": [ { "key": "P-KRISTINE18", "pmid": "29175149", "title": "Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29175149/", "doi": "10.1016/S1470-2045(17)30716-7", "errata": [] }, { "key": "P-KRISTINE19", "pmid": "31157583", "title": "Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.", "journal": "J Clin Oncol", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31157583/", "doi": "10.1200/JCO.19.00882", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Omitting conventional chemotherapy lowered toxicity but also lowered pathological response and allowed progression before surgery in some patients. The trial was not designed to select patients who could safely omit chemotherapy. The association of pathological response with outcome is prognostic, not a test of response-guided treatment. Both abstracts are one trial.", "label": "KRISTINE · neoadjuvant T-DM1 plus pertuzumab without conventional chemotherapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Neoadjuvant, then continued adjuvant HER2-directed therapy", "population": "HER2-positive stage II to III operable breast cancer", "claim": "In the phase 3 KRISTINE trial, 444 patients were assigned to trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 of 223 (44.4%) versus 123 of 221 (55.7%) (absolute difference -11.3 percentage points, 95% CI -20.5 to -2.0; p=0.016). Grade 3-4 adverse events during neoadjuvant treatment occurred in 13% versus 64%. At a median follow-up of 37 months, the risk of an event-free survival event was higher with trastuzumab emtansine plus pertuzumab (HR 2.61, 95% CI 1.36 to 4.98), with 15 (6.7%) locoregional progression events before surgery versus none; the risk of an invasive disease-free survival event after surgery was similar (HR 1.11, 95% CI 0.52 to 2.40). Pathological complete response was associated with a lower risk of an invasive event (HR 0.24, 95% CI 0.09 to 0.60) in both arms.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-KRISTINE", "nct": "NCT02131064", "acronym": null, "title": "A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 444, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-06-25", "lastUpdate": "2019-07-02", "url": "https://clinicaltrials.gov/study/NCT02131064" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathological complete response (ypT0/is, ypN0) in the intention-to-treat population, by local evaluation of surgical tumour samples", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 444, "assessment": "not stated", "quote": "We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres … The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery … we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221)." }, "effect": {}, "landmark": [ { "endpoint": "Pathological complete response", "timepoint": "At surgery after six neoadjuvant cycles", "experimental_pct": 44.4, "control_pct": 55.7, "higher_is_better": true, "experimental_arm": "Trastuzumab emtansine plus pertuzumab (T-DM1+P)", "control_arm": "Docetaxel, carboplatin, trastuzumab plus pertuzumab (TCH+P)", "quote": "T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016)", "difference_pp": -11.3, "nnt": null, "nnt_label": "favours control", "quote_note": "From the most recent paper, P-KRISTINE19 (J Clin Oncol 2019), which restates the primary result", "nnh": 9 } ], "harms": { "grade3plus_experimental_pct": 31.8, "grade3plus_control_pct": 67.7, "discontinuation_experimental_pct": 18.4, "discontinuation_control_pct": 3.8, "treatment_related_deaths": "No deaths were reported during neoadjuvant treatment; deaths over the full follow-up are not reported in the abstracts.", "quote": "Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. … No deaths were reported during neoadjuvant treatment.", "quote_note": "P-KRISTINE19; Discontinuation figures apply to the adjuvant phase only. P-KRISTINE18" }, "takeaway_en": "In 444 patients with HER2-positive stage II–III operable breast cancer, neoadjuvant trastuzumab emtansine plus pertuzumab gave a lower pathological complete response rate than docetaxel, carboplatin and trastuzumab plus pertuzumab (44.4% vs 55.7%, an absolute difference of -11.3 percentage points), and a higher risk of an event-free survival event (HR 2.61) driven by locoregional progression before surgery (6.7% vs 0); invasive disease-free survival after surgery was similar (HR 1.11). The chemotherapy-free regimen caused fewer grade 3 or higher adverse events overall (31.8% vs 67.7%), but during adjuvant treatment more patients stopped treatment because of adverse events (18.4% vs 3.8%).", "takeaway_ko": "HER2 양성 II–III기 수술 가능 유방암 환자 444명에서 수술 전 트라스투주맙 엠탄신(T-DM1)+퍼투주맙 요법은 도세탁셀·카보플라틴·트라스투주맙+퍼투주맙(TCH+P) 요법보다 병리학적 완전관해율이 낮았습니다(44.4% 대 55.7%, 절대 차이 -11.3%p). 무사건생존(EFS) 사건 위험도 더 높았는데(HR 2.61), 이는 수술 전 국소영역 진행(6.7% 대 0) 때문이었으며, 수술 후 침습적 무질병생존은 비슷했습니다(HR 1.11). 항암화학요법을 뺀 이 요법은 전체 3등급 이상 이상반응이 더 적었지만(31.8% 대 67.7%), 보조요법 기간에는 이상반응으로 치료를 중단한 비율이 더 높았습니다(18.4% 대 3.8%).", "certainty": { "level": "very low", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed", "no confidence interval for the primary effect in the abstract", "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-MONARCH2", "trial": "B-MONARCH2", "papers": [ { "key": "P-MONARCH2", "pmid": "28580882", "title": "MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy.", "journal": "J Clin Oncol", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28580882/", "doi": "10.1200/JCO.2017.73.7585", "errata": [] }, { "key": "P-MONARCH2OS", "pmid": "31563959", "title": "The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial.", "journal": "JAMA Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31563959/", "doi": "10.1001/jamaoncol.2019.4782", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Results for abemaciclib are not evidence about other CDK4/6 inhibitors; a trial of palbociclib in a similar setting did not show a significant overall survival difference, and no cross-trial comparison is made here. Patients had not received a CDK4/6 inhibitor before. The subgroup findings in the survival report are not separate tests. Both abstracts are one trial.", "label": "MONARCH 2 · abemaciclib plus fulvestrant after endocrine therapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Advanced disease that progressed while receiving endocrine therapy", "population": "HR-positive, HER2-negative advanced breast cancer", "claim": "In the phase 3 MONARCH 2 trial, 669 patients were assigned to abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Median progression-free survival was 16.4 versus 9.3 months (hazard ratio 0.553; 95% CI 0.449 to 0.681). Diarrhoea occurred in 86.4% versus 24.7% and neutropenia in 46.0% versus 4.0%. At the prespecified interim overall survival analysis after 338 deaths, median overall survival was 46.7 versus 37.3 months (HR 0.757; 95% CI 0.606-0.945; P = .01). Median time to chemotherapy was 50.2 versus 22.1 months.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-MONARCH2", "nct": "NCT02107703", "acronym": "MONARCH 2", "title": "A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 669, "sponsor": "Eli Lilly and Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-07-22", "lastUpdate": "2026-10-14", "url": "https://clinicaltrials.gov/study/NCT02107703" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival (PFS)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 669, "assessment": "investigator", "quote": "MONARCH 2 was a global, double-blind, phase III study … Patients were randomly assigned 2:1 to receive abemaciclib or placebo … The primary end point was investigator-assessed progression-free survival (PFS) … 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223)." }, "effect": { "measure": "HR", "value": 0.553, "ci_low": 0.449, "ci_high": 0.681, "ci_level": "95%", "p": "P < .001", "endpoint": "Progression-free survival", "quote": "Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001)." }, "landmark": [ { "endpoint": "Objective response rate (patients with measurable disease)", "timepoint": "Primary analysis (J Clin Oncol 2017)", "experimental_pct": 48.1, "control_pct": 21.3, "higher_is_better": true, "experimental_arm": "Abemaciclib plus fulvestrant", "control_arm": "Placebo plus fulvestrant", "quote": "In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm.", "difference_pp": 26.8, "nnt": 4, "quote_note": "From the J Clin Oncol 2017 primary report, the only paper reporting ORR" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%)." }, "takeaway_en": "In 669 women with HR-positive, HER2-negative advanced breast cancer that progressed on endocrine therapy, abemaciclib plus fulvestrant was compared with placebo plus fulvestrant. The objective response rate in measurable disease was 48.1% vs 21.3% (PFS hazard ratio 0.553), and median overall survival at the interim analysis was 46.7 vs 37.3 months. The main trade-off was more diarrhea (86.4% vs 24.7%) and neutropenia (46.0% vs 4.0%), reported as any-grade events; grade 3 or higher rates were not given in the abstracts.", "takeaway_ko": "내분비요법 중 진행한 HR 양성, HER2 음성 진행성 유방암 여성 669명에서 아베마시클립+풀베스트란트를 위약+풀베스트란트와 비교했습니다. 측정 가능 병변 환자의 객관적 반응률은 48.1% 대 21.3%(무진행생존 위험비 0.553)였고, 중간 분석에서 전체생존 중앙값은 46.7개월 대 37.3개월이었습니다. 주요 대가는 설사(86.4% 대 24.7%)와 호중구감소증(46.0% 대 4.0%)의 증가였으며, 이는 모든 등급 기준이고 3등급 이상 비율은 초록에 보고되지 않았습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ML7", "trial": "B-ML7", "papers": [ { "key": "P-ML7", "pmid": "29804902", "title": "Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.", "journal": "Lancet Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29804902/", "doi": "10.1016/S1470-2045(18)30292-4", "errata": [] }, { "key": "P-ML7OS", "pmid": "31166679", "title": "Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.", "journal": "N Engl J Med", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31166679/", "doi": "10.1056/NEJMoa1903765", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Population is premenopausal women receiving ovarian suppression; no extrapolation to other settings or to other CDK4/6 inhibitors. The 42-month estimate in the placebo group has a wide interval (32.0 to 58.9 in the abstract). Both abstracts are one trial.", "label": "MONALEESA-7 · ribociclib plus endocrine therapy before menopause", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First-line endocrine-based therapy for advanced disease, with ovarian suppression", "population": "Premenopausal or perimenopausal women with HR-positive, HER2-negative advanced breast cancer", "claim": "In the phase 3 MONALEESA-7 trial, 672 patients were assigned to ribociclib (335) or placebo (337) with endocrine therapy. Median progression-free survival was 23.8 versus 13.0 months (hazard ratio 0.55, 95% CI 0.44-0.69). Grade 3 or 4 neutropenia occurred in 61% versus 4%. In the overall survival analysis there were 83 deaths among 335 patients (24.8%) versus 109 among 337 (32.3%); estimated overall survival at 42 months was 70.2% versus 46.0% (hazard ratio for death 0.71; 95% CI 0.54 to 0.95; P = 0.00973).", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-ML7", "nct": "NCT02278120", "acronym": "MONALEESA-7", "title": "Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 672, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2014-11-20", "lastUpdate": "2024-03-12", "url": "https://clinicaltrials.gov/study/NCT02278120" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 672, "assessment": "investigator", "quote": "This phase 3, randomised, double-blind, placebo-controlled trial was done at 188 centres in 30 countries. … The primary endpoint was investigator-assessed progression-free survival. … 672 patients were randomly assigned: 335 to the ribociclib group and 337 to the placebo group." }, "effect": { "measure": "HR", "value": 0.55, "ci_low": 0.44, "ci_high": 0.69, "ci_level": "95%", "p": "p<0·0001", "endpoint": "Investigator-assessed progression-free survival", "quote": "Per investigator's assessment, median progression-free survival was 23·8 months (95% CI 19·2-not reached) in the ribociclib group compared with 13·0 months (11·0-16·4) in the placebo group (hazard ratio 0·55, 95% CI 0·44-0·69; p<0·0001)." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "42 months", "experimental_pct": 70.2, "control_pct": 46, "higher_is_better": true, "experimental_arm": "Ribociclib plus endocrine therapy (goserelin plus NSAI or tamoxifen)", "control_arm": "Placebo plus endocrine therapy (goserelin plus NSAI or tamoxifen)", "quote": "The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test).", "difference_pp": 24.2, "nnt": 5, "quote_note": "N Engl J Med 2019 protocol-specified interim OS analysis (most recent paper" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 4, "discontinuation_control_pct": 3, "treatment_related_deaths": "No treatment-related deaths occurred.", "quote": "Grade 3 or 4 adverse events reported in more than 10% of patients in either group were neutropenia (203 [61%] of 335 patients in the ribociclib group and 12 [4%] of 337 in the placebo group) and leucopenia (48 [14%] and four [1%]). … 12 (4%) of 335 patients in the ribociclib group and ten (3%) of 337 in the placebo group discontinued treatment because of adverse events. No treatment-related deaths occurred." }, "takeaway_en": "In premenopausal or perimenopausal women with HR-positive, HER2-negative advanced breast cancer receiving goserelin plus an aromatase inhibitor or tamoxifen, adding ribociclib instead of placebo lengthened median progression-free survival from 13.0 to 23.8 months (HR 0.55). In an interim analysis, estimated 42-month overall survival was 70.2% versus 46.0%. The main trade-off was grade 3 or 4 neutropenia in 61% versus 4% of patients, although discontinuation because of adverse events was similar (4% vs 3%).", "takeaway_ko": "고세렐린과 아로마타제 억제제 또는 타목시펜 내분비요법을 받는 폐경 전 또는 폐경 주변기 HR 양성, HER2 음성 진행성 유방암 여성에서 위약 대신 리보시클립을 추가하자 무진행생존기간 중앙값이 13.0개월에서 23.8개월로 연장되었습니다(위험비 0.55). 중간분석에서 42개월 추정 전체생존율은 70.2% 대 46.0%였습니다. 주요 대가는 3-4등급 호중구감소증(61% 대 4%)이었으나, 이상반응으로 인한 치료 중단율은 비슷했습니다(4% 대 3%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PATINA", "trial": "B-PATINA", "papers": [ { "key": "P-PATINA26", "pmid": "41604639", "title": "Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41604639/", "doi": "10.1056/NEJMoa2511218", "errata": [] } ], "pages": [], "targets": [ "CDK4/6", "ERBB2" ], "biomarkers": [ "BM-HER2-B", "BM-HR" ], "subtypes": [ "B-HER2POS", "B-HRPOS" ], "limits": "Open-label trial with progression-free survival as the end point; overall survival is not reported in this abstract. Only patients without progression after induction therapy were randomised. The upper confidence bound is close to 1 and toxicity was substantially higher.", "label": "PATINA · palbociclib added to maintenance HER2 and endocrine therapy", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Maintenance after first-line induction chemotherapy with dual HER2 therapy", "population": "Hormone receptor-positive, HER2-positive metastatic breast cancer", "claim": "In the open-label phase 3 PATINA trial, 518 patients were randomised: 261 to palbociclib added to anti-HER2 and endocrine maintenance and 257 to standard maintenance. At a median follow-up of 53.5 months, median progression-free survival was 44.3 versus 29.1 months (hazard ratio 0.75; 95% CI 0.59 to 0.96; two-sided P = 0.02). Grade 3 and grade 4 adverse events occurred in 79.7% and 10.0% of the palbociclib group versus 30.6% and 3.6% of the standard-therapy group, mainly neutropenia.", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "B-PATINA", "nct": "NCT02947685", "acronym": "PATINA", "title": "Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 518, "sponsor": "Alliance Foundation Trials, LLC.", "sponsorClass": "OTHER", "collaborators": [ "Pfizer", "GBG Forschungs GmbH", "Fondazione Michelangelo", "PrECOG, LLC.", "Breast Cancer Trials, Australia and New Zealand", "Syneos Health", "SOLTI Breast Cancer Research Group", "UNICANCER" ], "hasResults": true, "start": "2017-06-21", "lastUpdate": "2026-10-22", "url": "https://clinicaltrials.gov/study/NCT02947685" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Investigator-assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 518, "assessment": "investigator", "quote": "In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. … The primary end point was investigator-assessed progression-free survival. … A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy." }, "effect": { "measure": "HR", "value": 0.75, "ci_low": 0.59, "ci_high": 0.96, "ci_level": "95%", "p": "two-sided P = 0.02", "endpoint": "Progression-free survival (disease progression or death)", "quote": "At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group.", "quote_note": "Grade 3 and grade 4 are reported separately, not as a combined grade 3 or higher rate." }, "takeaway_en": "In 518 patients with hormone receptor-positive, HER2-positive metastatic breast cancer without progression after induction chemotherapy plus HER2-targeted therapy, adding palbociclib to maintenance HER2-targeted and endocrine therapy prolonged investigator-assessed progression-free survival (median 44.3 vs 29.1 months; hazard ratio 0.75, 95% CI 0.59 to 0.96) at a median follow-up of 53.5 months. The trade-off was more toxicity, mainly neutropenia: grade 3 adverse events occurred in 79.7% vs 30.6% and grade 4 in 10.0% vs 3.6%.", "takeaway_ko": "HER2 표적치료를 병용한 유도 항암화학요법 후 진행이 없었던 호르몬수용체 양성, HER2 양성 전이성 유방암 환자 518명에서, 유지 HER2 표적치료 및 내분비요법에 팔보시클립을 추가하자 연구자 평가 무진행생존기간이 연장되었습니다(중앙 추적관찰 53.5개월 시점, 중앙값 44.3개월 대 29.1개월; 위험비 0.75, 95% 신뢰구간 0.59–0.96). 대신 독성이 증가했으며 주로 호중구감소증이었습니다. 3등급 이상반응은 79.7% 대 30.6%, 4등급 이상반응은 10.0% 대 3.6%에서 발생했습니다.", "certainty": { "level": "moderate", "reasons": [ "open-label with a non-survival endpoint not centrally reviewed" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ctDNAEGCpCR24", "trial": null, "papers": [ { "key": "P-ctDNAEGCpCR24", "pmid": "39642325", "title": "Circulating Tumor DNA as a Prognostic Biomarker for Recurrence in Patients With Locoregional Esophagogastric Cancers With a Pathologic Complete Response.", "journal": "JCO Precis Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39642325/", "doi": "10.1200/PO.24.00288", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Very small numbers: three ctDNA-positive patients in the early window and five during surveillance, so the hazard ratios are unstable and the first is at the margin of significance. Prognostic association only; no intervention was tested. Esophageal and junctional tumours are included with gastric tumours. Three of 20 patients without detectable ctDNA still recurred.", "label": "Postoperative ctDNA after a pathological complete response · esophagogastric", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "After neoadjuvant therapy and surgery with a pathological complete response", "population": "42 patients with locoregional esophagogastric adenocarcinoma at one centre", "claim": "Among 42 patients (309 blood samples) followed for a median of 28.5 months, 23 were tested in the 16-week postoperative window; recurrence occurred in 2 of 3 patients (67%) with detectable ctDNA versus 3 of 20 (15%) with undetectable ctDNA (hazard ratio 6.2; P = .049). In 32 patients tested during surveillance, recurrence occurred in 5 of 5 ctDNA-positive patients (100%) versus 2 of 27 (7.4%) ctDNA-negative patients (hazard ratio 37.6).", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ctDNAGC25", "trial": null, "papers": [ { "key": "P-ctDNAGC25", "pmid": "39369091", "title": "Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.", "journal": "Gastric Cancer", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39369091/", "doi": "10.1007/s10120-024-01556-9", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Eighty-six patients; not every patient had a sample at every time point, and the abstract does not give the numbers behind each percentage. ctDNA was undetected in 44% at baseline, so a negative result later may reflect a tumour that does not shed. Prognostic association only; the authors state that ctDNA-guided intervention still needs testing.", "label": "ctDNA through perioperative chemotherapy and surgery · gastric and junctional", "program": "gastric", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Perioperative chemotherapy and resection, with serial plasma sampling", "population": "86 patients with resectable gastric or gastroesophageal junction cancer", "claim": "In 229 plasma samples from 86 patients, ctDNA was detected in 56% at baseline, 37% after one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after resection. ctDNA after one cycle was associated with shorter recurrence-free survival (HR = 2.54, 95% CI 1.33-4.85) and overall survival (HR = 2.23, 95% CI 1.07-4.62). ctDNA after surgery was associated with shorter recurrence-free survival (HR = 6.22, 95% CI 2.39-16.2) and overall survival (HR = 6.37, 95% CI 2.10-19.3) and remained an independent factor in multivariable analysis.", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ctDNAGarcia19", "trial": null, "papers": [ { "key": "P-ctDNAGarcia19", "pmid": "31369045", "title": "Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer.", "journal": "JAMA Oncol", "year": "2019", "url": "https://pubmed.ncbi.nlm.nih.gov/31369045/", "doi": "10.1001/jamaoncol.2019.1838", "errata": [ { "pmid": "31917389", "title": "Errors in Results.", "url": "https://pubmed.ncbi.nlm.nih.gov/31917389/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Confidence intervals are wide. Brain-only relapse was mostly missed. A published correction to the Results states that 6 of the 29 patients who relapsed (20.7%) had no ctDNA detection before or at relapse. The study shows prognostic association and lead time, not that acting on a positive result improves outcome; the authors call for prospective studies of guided therapy.", "label": "Molecular relapse detection in early breast cancer · multicentre validation", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Serial plasma sampling after treatment of early-stage disease", "population": "101 women with early-stage breast cancer in the main cohort, across subtypes", "claim": "In the main cohort of 101 patients with a median follow-up of 35.5 months, ctDNA detection during follow-up was associated with relapse (hazard ratio 25.2; 95% CI 6.7-95.6). Detection at diagnosis was also associated with relapse-free survival (hazard ratio 5.8; 95% CI 1.2-27.1). In the combined cohort, ctDNA detection preceded clinical relapse by a median of 10.7 months (95% CI 8.1-19.1). Distant extracranial relapse was detected by ctDNA in 22 of 23 patients (96%), but brain-only metastasis in 1 of 6 patients (17%).", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 1, "analysisRecord": null }, { "id": "U-ctDNAISPY23", "trial": null, "papers": [ { "key": "P-ctDNAISPY23", "pmid": "37146605", "title": "Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy.", "journal": "Cancer Cell", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37146605/", "doi": "10.1016/j.ccell.2023.04.008", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS", "B-TNBC" ], "limits": "The abstract gives no counts, rates or effect sizes. A correlative analysis within a trial, not a test of changing treatment by ctDNA; the authors state that the platform trial will test this prospectively. Lower shedding in hormone receptor-positive disease means a negative result carries less information there.", "label": "ctDNA during neoadjuvant chemotherapy by subtype · I-SPY2", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Serial personalised ctDNA testing before, during and after neoadjuvant chemotherapy", "population": "High-risk early-stage HER2-negative breast cancer (hormone receptor-positive and triple-negative) in a neoadjuvant platform trial", "claim": "ctDNA positivity before, during and after neoadjuvant chemotherapy was more frequent in triple-negative than in hormone receptor-positive, HER2-negative disease. Early ctDNA clearance 3 weeks after starting treatment predicted a favourable response only in triple-negative disease. ctDNA positivity was associated with shorter distant recurrence-free survival in both subtypes, and ctDNA negativity after chemotherapy with better outcome even in patients with extensive residual cancer.", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ctDNALate22", "trial": null, "papers": [ { "key": "P-ctDNALate22", "pmid": "35658506", "title": "Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35658506/", "doi": "10.1200/JCO.22.00908", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Six distant recurrences in two years of follow-up from the first sample; late recurrence continues for many more years, so negative results are not shown to be reassuring long term. Two test-positive patients had not recurred. Twenty patients could not be tested for lack of tissue or sequencing. No intervention was tested.", "label": "ctDNA and late recurrence in hormone receptor-positive breast cancer", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Late adjuvant period, more than 5 years from diagnosis", "population": "103 enrolled patients with high-risk early-stage hormone receptor-positive, HER2-negative breast cancer; 83 with successful tumour sequencing", "claim": "Of 103 enrolled patients, 85 had sufficient tumour tissue and 83 of 85 (97.6%) had successful whole-exome sequencing; 219 plasma samples were tested. The median time from diagnosis to first sample was 8.4 years and follow-up from first sample 2.0 years. Eight patients (10%) had a positive residual-disease test at any time. Six patients (7.2%) developed distant recurrence, all of them test-positive beforehand with a median lead time of 12.4 months. One patient (1.2%) with local recurrence was not identified. Two of the eight test-positive patients had not recurred at last follow-up.", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ctDNALongit25", "trial": null, "papers": [ { "key": "P-ctDNALongit25", "pmid": "39424680", "title": "Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer.", "journal": "Breast Cancer Res Treat", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39424680/", "doi": "10.1007/s10549-024-07508-2", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Thirteen relapses; three were missed. Sixty-one patients make the 100% figures imprecise, and the abstract gives no interval for them. The assay is a commercial product named in the abstract. Lead time is not benefit: no treatment was changed on the result.", "label": "Longitudinal personalised ctDNA monitoring in early breast cancer", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Monitoring after treatment of early disease with a commercial tumour-informed assay", "population": "61 patients with early breast cancer in the monitoring phase", "claim": "Sensitivity for patients who relapsed during monitoring was 76.9% (10/13). All 10 of 61 patients (16%) with ctDNA detected during monitoring later relapsed, giving specificity and positive predictive value of 100%. ctDNA detection was associated with relapse (HR 37.2, 95% CI 10.5-131.9), with a median lead time of 11.7 months.", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-T-ZETA", "trial": "T-ZETA", "papers": [ { "key": "P-T-ZETA12", "pmid": "22025146", "title": "Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.", "journal": "J Clin Oncol", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22025146/", "doi": "10.1200/JCO.2011.35.5040", "errata": [ { "pmid": null, "title": "J Clin Oncol. 2013 Aug 20;31(24):3049", "url": "https://pubmed.ncbi.nlm.nih.gov/22025146/", "reviewed": false, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Progression-free survival was the primary end point; overall survival was immature at this cutoff and patients could cross over to open-label vandetanib after progression, so a survival effect is not shown. Patients were not required to have documented progression before entry. The abstract does not give results by RET mutation status. Placebo-controlled; it does not compare vandetanib with cabozantinib or with selective RET inhibitors.", "label": "ZETA (vandetanib, medullary thyroid cancer)", "kind": "rct", "result": "positive", "setting": "Randomized, double-blind phase III trial of vandetanib 300 mg/d versus placebo, assigned 2:1; open-label vandetanib was allowed after objective progression.", "population": "331 patients with locally advanced or metastatic medullary thyroid cancer (90% sporadic; 95% metastatic), randomly assigned between December 2006 and November 2007.", "claim": "Of 331 patients, 231 were assigned to vandetanib and 100 to placebo. At a median follow-up of 24 months, 37% of patients had progressed and 15% had died. Progression-free survival by independent central review was longer with vandetanib (HR 0.46; 95% CI 0.31 to 0.69; P < .001). Overall survival data were immature (HR 0.89; 95% CI 0.48 to 1.65). Adverse events of any grade were more frequent with vandetanib than placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%) and headache (26% v 9%).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "T-ZETA", "nct": "NCT00410761", "acronym": null, "title": "An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 331, "sponsor": "Genzyme, a Sanofi Company", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2006-11-23", "lastUpdate": "2025-09-24", "url": "https://clinicaltrials.gov/study/NCT00410761" }, "sources": 2, "corrections": 1, "analysisRecord": null }, { "id": "U-T-EXAM", "trial": "T-EXAM", "papers": [ { "key": "P-T-EXAM13", "pmid": "24002501", "title": "Cabozantinib in progressive medullary thyroid cancer.", "journal": "J Clin Oncol", "year": "2013", "url": "https://pubmed.ncbi.nlm.nih.gov/24002501/", "doi": "10.1200/JCO.2012.48.4659", "errata": [ { "pmid": null, "title": "J Clin Oncol. 2014 Jun 10;32(17):1864", "url": "https://pubmed.ncbi.nlm.nih.gov/24002501/", "reviewed": false, "unresolvedIdentifier": true } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Progression-free survival was the primary end point; the abstract reports no overall survival result. Entry required documented radiographic progression, unlike the vandetanib trial, so the two placebo arms and hazard ratios are not comparable across trials. Dose reductions and holds were frequent at this dose. Placebo-controlled; it does not compare cabozantinib with vandetanib or with selective RET inhibitors.", "label": "EXAM (cabozantinib, medullary thyroid cancer)", "kind": "rct", "result": "positive", "setting": "Double-blind phase III trial of cabozantinib 140 mg per day versus placebo, assigned 2:1.", "population": "330 patients with documented radiographic progression of metastatic medullary thyroid cancer.", "claim": "Estimated median progression-free survival was 11.2 months with cabozantinib versus 4.0 months with placebo (HR 0.28; 95% CI 0.19 to 0.40; P < .001). Response rate was 28% with cabozantinib and 0% with placebo. Kaplan-Meier estimates of the proportion of patients alive and progression-free at 1 year were 47.3% and 7.2%. Cabozantinib-associated adverse events led to dose reductions in 79% and holds in 65% of patients; adverse events led to treatment discontinuation in 16% of cabozantinib-treated and 8% of placebo-treated patients.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "T-EXAM", "nct": "NCT00704730", "acronym": "EXAM", "title": "Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 330, "sponsor": "Exelixis", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2008-06", "lastUpdate": "2021-04-20", "url": "https://clinicaltrials.gov/study/NCT00704730" }, "sources": 2, "corrections": 1, "analysisRecord": null }, { "id": "U-T-ARROW", "trial": "T-ARROW", "papers": [ { "key": "P-T-ARROW21", "pmid": "34118198", "title": "Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.", "journal": "Lancet Diabetes Endocrinol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34118198/", "doi": "10.1016/S2213-8587(21)00120-0", "errata": [ { "pmid": "34534460", "title": "Correction to Lancet Diabetes Endocrinol 2021; 9: 491-501.", "url": "https://pubmed.ncbi.nlm.nih.gov/34534460/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Uncontrolled cohorts at an interim analysis; response rates are not comparative effects and the fusion-positive group had nine evaluable patients. The efficacy denominators (21, 55 and nine) are smaller than the 142-patient safety population and must not be combined. The abstract reports no progression-free or overall survival result. It does not compare pralsetinib with selpercatinib, cabozantinib or vandetanib.", "label": "ARROW (pralsetinib, RET-altered thyroid cohorts)", "kind": "single-arm", "result": "positive", "setting": "Pralsetinib 400 mg once daily in the RET-altered thyroid cancer cohorts of a phase 1/2, open-label, multi-cohort study; response by masked independent central review. Interim analysis.", "population": "122 patients with RET-mutant medullary and 20 with RET fusion-positive thyroid cancer enrolled by May 22, 2020; efficacy in those with measurable disease who received pralsetinib by July 11, 2019.", "claim": "Overall response rates were 15 (71%) of 21 (95% CI 48-89) in treatment-naive RET-mutant medullary thyroid cancer, 33 (60%) of 55 (95% CI 46-73) in patients previously given cabozantinib or vandetanib, or both, and eight (89%) of nine (95% CI 52-100) in RET fusion-positive thyroid cancer. Among 142 patients with RET-altered thyroid cancer, grade 3 and above treatment-related adverse events included hypertension in 24 patients (17%), neutropenia in 19 (13%), lymphopenia in 17 (12%) and anaemia in 14 (10%). Serious treatment-related adverse events were reported in 21 patients (15%), most often pneumonitis (five patients, 4%). Five patients (4%) discontinued owing to treatment-related events and one (1%) died owing to a treatment-related adverse event.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "T-ARROW", "nct": "NCT03037385", "acronym": "ARROW", "title": "Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors", "status": "COMPLETED", "phases": [ "PHASE1", "PHASE2" ], "enrollment": 590, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2017-03-17", "lastUpdate": "2025-05-31", "url": "https://clinicaltrials.gov/study/NCT03037385" }, "sources": 2, "corrections": 1, "analysisRecord": null }, { "id": "U-T-LaroThyroid22", "trial": "T-NAVIGATE", "papers": [ { "key": "P-T-LaroThyroid22", "pmid": "35333737", "title": "Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma.", "journal": "Eur J Endocrinol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35333737/", "doi": "10.1530/EJE-21-1259", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A pooled, uncontrolled analysis of 29 patients drawn from three trials; response was assessed by investigators, not by independent review. Only 7 patients had anaplastic carcinoma and the interval for their response rate is wide. The trial link names one of the three pooled trials. The abstract gives no frequency for higher-grade adverse events. TRK fusions are uncommon in thyroid cancer, and these results say nothing about tumours without a fusion.", "label": "Larotrectinib in TRK fusion-positive thyroid carcinoma · pooled analysis of three trials", "kind": "single-arm", "result": "positive", "setting": "Pooled data from three phase I/II larotrectinib trials (NCT02576431, NCT02122913 and NCT02637687); investigator-assessed response; data cut-off July 2020.", "population": "Twenty-nine patients (age range 6-80) with TRK fusion-positive thyroid carcinoma: papillary in 20 (69%), follicular in 2 (7%) and anaplastic in 7 (24%).", "claim": "Among 28 evaluable patients, the objective response rate was 71% (95% CI 51-87), with complete response in 2 (7%) and partial response in 18 (64%). The response rate was 86% (95% CI 64-97) for papillary or follicular carcinoma and 29% (95% CI 4-71) for anaplastic carcinoma. The 24-month rates of duration of response, progression-free survival and overall survival were 81, 69 and 76%. Treatment-related adverse events were mainly grades 1-2.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": { "key": "T-NAVIGATE", "nct": "NCT02576431", "acronym": "NAVIGATE", "title": "A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 215, "sponsor": "Bayer", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2015-09-30", "lastUpdate": "2026-07-01", "url": "https://clinicaltrials.gov/study/NCT02576431" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-PTMCObserveAge14", "trial": null, "papers": [ { "key": "P-PTMCObserveAge14", "pmid": "24001104", "title": "Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation.", "journal": "Thyroid", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/24001104/", "doi": "10.1089/thy.2013.0367", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Observational, single institution; patients chose observation, so they are not comparable with patients who had immediate surgery and no surgical comparison group is reported. The abstract gives no progression percentages by age group. The cohort is adults with an already diagnosed low-risk microcarcinoma; it says nothing about people without a cancer diagnosis, about children, or about larger or higher-risk tumours. Absence of distant metastasis or death over an average of 75 months does not establish lifelong safety.", "label": "Low-risk papillary microcarcinoma under observation · progression by age in a Japanese cohort", "kind": "observational", "result": "descriptive", "setting": "Single-institution cohort of patients who chose observation without immediate surgery between 1993 and 2011, followed periodically with ultrasound; observation periods 18 to 227 months (average 75 months).", "population": "1235 patients with low-risk papillary thyroid microcarcinoma, grouped by age at the start of observation: young (<40 years), middle-aged (40-59 years) and old (≥60 years).", "claim": "Progression was assessed as tumor enlargement, new lymph node metastasis, or progression to clinical disease (a tumor size of 12 mm or larger, or new nodal metastasis). The proportion with progression was lowest in the oldest patients and highest in the youngest patients, and young age was an independent predictor of progression on multivariate analysis. None of the 1235 patients showed distant metastasis or died of papillary cancer during observation. After observation, 191 patients underwent surgery for various reasons; only one had a recurrence, in the residual thyroid, and none died of papillary cancer after surgery.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PTCSurveillanceUS17", "trial": null, "papers": [ { "key": "P-PTCSurveillanceUS17", "pmid": "28859191", "title": "Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance.", "journal": "JAMA Otolaryngol Head Neck Surg", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28859191/", "doi": "10.1001/jamaoto.2017.1442", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Observational, single tertiary center with a median surveillance of 25 months; the 5-year estimate rests on few patients followed that long. Patients were selected for surveillance and no surgical comparison group is reported. Adults with an already diagnosed low-risk cancer; it says nothing about people without a cancer diagnosis or about children. Absence of metastasis over this follow-up does not establish long-term safety.", "label": "Low-risk papillary thyroid cancer under active surveillance · tumour growth in a United States cohort", "kind": "observational", "result": "descriptive", "setting": "Cohort study at a tertiary referral center in the United States with serial ultrasonographic tumour measurements; median (range) active surveillance of 25 (6-166) months.", "population": "291 patients under active surveillance for low-risk papillary thyroid cancer (intrathyroidal tumors ≤1.5 cm); 219 (75.3%) were women; mean (SD) age 52 (15) years.", "claim": "Growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with cumulative incidences of 2.5% at 2 years and 12.1% at 5 years. No regional or distant metastases developed during active surveillance. Younger age at diagnosis was independently associated with the likelihood of tumor growth (hazard ratio per year, 0.92; 95% CI 0.87-0.98; P = .006). For tumors that grew in volume, the median doubling time was 2.2 years (range 0.5-4.8 years).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-07", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-IM050", "trial": "B-IM050", "papers": [ { "key": "P-IM050primary", "pmid": "35763704", "title": "Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35763704/", "doi": "10.1200/JCO.21.02772", "errata": [] }, { "key": "P-IM050final26", "pmid": "42785163", "title": "Atezolizumab plus pertuzumab, trastuzumab, and chemotherapy in HER2-positive early breast cancer: final results of the phase III IMpassion050 trial.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42785163/", "doi": "10.1016/j.esmoop.2026.108541", "errata": [] } ], "pages": [], "targets": [ "ERBB2", "CD274" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Final EFS and DFS are secondary outcomes; DFS uses a postsurgery/postneoadjuvant subset rather than the full randomized population. Wide intervals do not establish equivalence or absence of every possible benefit. Numerical subgroup differences do not demonstrate an interaction. The final adjuvant safety subset does not erase fatal events reported earlier. Primary and follow-up publications are the same trial and count once. The saved abstracts and current registry were checked; full protocol, analysis plan and supplements were not independently reviewed.", "by": "Codex (GPT-6)", "added": "2026-10-07", "label": "IMpassion050: primary response and final follow-up", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Neoadjuvant and adjuvant therapy for high-risk early disease", "population": "HER2-positive early breast cancer with node-positive disease", "claim": "Adding atezolizumab to pertuzumab, trastuzumab and chemotherapy did not increase primary pCR: 62.4% versus 62.7% with placebo. Final follow-up reported 3-year EFS of 91.4% versus 89.0% (stratified HR 0.90; 95% CI 0.50-1.59). DFS in the postsurgery population was 92.9% versus 88.5% (HR 0.71; 95% CI 0.38-1.32). Neither survival comparison was significant. Adjuvant adverse events of special interest were 59.4% versus 47.0%; the primary report had described 5 grade-5 adverse events, all in the atezolizumab group, with 2 assigned to study treatment.", "trialRecord": { "key": "B-IM050", "nct": "NCT03726879", "acronym": "IMpassion050", "title": "A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 454, "sponsor": "Hoffmann-La Roche", "sponsorClass": "INDUSTRY", "collaborators": [ "Chugai Pharmaceutical" ], "hasResults": true, "start": "2019-01-11", "lastUpdate": "2024-11-05", "url": "https://clinicaltrials.gov/study/NCT03726879" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Pathologic complete response (pCR; ypT0/is ypN0) rate in the intention-to-treat and PD-L1-positive populations (coprimary)", "primary_endpoint_type": "pCR", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 454, "assessment": "not stated", "quote": "Primary Results of the Randomized Phase III IMpassion050 Trial … randomly assigned 1:1 to atezolizumab/placebo with dose-dense doxorubicin/cyclophosphamide, followed by paclitaxel, and PH. … At data cut-off (24 August 2023), 411/454 patients remained on-study (atezolizumab arm, 206/226; placebo arm, 205/228)." }, "effect": {}, "landmark": [ { "endpoint": "pCR, ITT population", "timepoint": "at surgery (primary analysis)", "experimental_pct": 62.4, "control_pct": 62.7, "higher_is_better": true, "experimental_arm": "Atezolizumab + pertuzumab-trastuzumab + chemotherapy", "control_arm": "Placebo + pertuzumab-trastuzumab + chemotherapy", "quote": "pCR rates in the placebo and atezolizumab groups in the ITT populations were 62.7% (n = 143/228) and 62.4% (n = 141/226), respectively", "difference_pp": -0.3, "nnt": null, "nnt_label": "favours control", "quote_note": "Primary paper (J Clin Oncol 2022", "nnh": 334 }, { "endpoint": "pCR, PD-L1-positive population", "timepoint": "at surgery (primary analysis)", "experimental_pct": 64.2, "control_pct": 72.5, "higher_is_better": true, "experimental_arm": "Atezolizumab + pertuzumab-trastuzumab + chemotherapy", "control_arm": "Placebo + pertuzumab-trastuzumab + chemotherapy", "quote": "The pCR rates in the placebo and atezolizumab groups in patients with PD-L1-positive tumors were 72.5% (n = 79/109) and 64.2% (n = 70/109), respectively", "difference_pp": -8.3, "nnt": null, "nnt_label": "favours control", "quote_note": "Primary paper (J Clin Oncol 2022", "nnh": 13 }, { "endpoint": "Event-free survival", "timepoint": "3 years", "experimental_pct": 91.4, "control_pct": 89, "higher_is_better": true, "experimental_arm": "Atezolizumab + pertuzumab-trastuzumab + chemotherapy", "control_arm": "Placebo + pertuzumab-trastuzumab + chemotherapy", "quote": "Three-year EFS rates were 91.4% (atezolizumab) versus 89.0% {placebo [stratified hazard ratio 0.90, 95% confidence interval (CI) 0.50-1.59]}.", "difference_pp": 2.4, "nnt": 42, "quote_note": "Final paper (ESMO Open 2026" }, { "endpoint": "Disease-free survival (patients who had surgery and postneoadjuvant therapy)", "timepoint": "3 years", "experimental_pct": 92.9, "control_pct": 88.5, "higher_is_better": true, "experimental_arm": "Atezolizumab + pertuzumab-trastuzumab + chemotherapy", "control_arm": "Placebo + pertuzumab-trastuzumab + chemotherapy", "quote": "Among patients who had surgery and postneoadjuvant therapy (n = 434), 3-year DFS rates were 92.9% (atezolizumab) versus 88.5% [placebo (hazard ratio 0.71, 95% CI 0.38-1.32)].", "difference_pp": 4.4, "nnt": 23, "quote_note": "Final paper (ESMO Open 2026" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Five grade 5 adverse events, all with atezolizumab (four neoadjuvant, one adjuvant); two were assigned to study treatment", "quote": "Grade 3-4 and serious adverse events were more frequent in the atezolizumab versus placebo group. Five grade 5 adverse events occurred (four neoadjuvant, one adjuvant; two assigned to study treatment), all with atezolizumab. … Adverse events (AEs) of special interest in the adjuvant setting were more frequent with atezolizumab (59.4% versus 47.0%; none grade 5).", "quote_note": "Primary paper; Final paper" }, "takeaway_en": "In patients with high-risk, node-positive HER2-positive early breast cancer, adding atezolizumab to neoadjuvant pertuzumab, trastuzumab and chemotherapy did not raise pCR (62.4% vs 62.7% with placebo). At final follow-up, 3-year EFS was 91.4% vs 89.0% (HR 0.90; 95% CI 0.50-1.59), a non-significant difference; atezolizumab brought more grade 3-4 and serious adverse events and more adjuvant adverse events of special interest (59.4% vs 47.0%). All five grade 5 events occurred in the atezolizumab arm, two of them attributed to study treatment.", "takeaway_ko": "고위험 림프절 양성 HER2 양성 조기 유방암 환자에서 선행 퍼투주맙·트라스투주맙·항암화학요법에 아테졸리주맙을 추가해도 병리학적 완전관해(pCR)율은 높아지지 않았습니다(62.4% 대 위약군 62.7%). 최종 추적에서 3년 무사건생존율은 91.4% 대 89.0%(HR 0.90; 95% CI 0.50-1.59)로 유의한 차이가 없었고, 아테졸리주맙군에서 3-4등급 및 중대한 이상반응이 더 많았으며 보조요법 기간의 특별관심 이상반응도 더 흔했습니다(59.4% 대 47.0%). 5등급 이상반응 5건은 모두 아테졸리주맙군에서 발생했으며, 그중 2건은 연구 치료와 관련된 것으로 판정되었습니다.", "certainty": { "level": "low", "reasons": [ "no confidence interval for the primary effect in the abstract", "surrogate primary endpoint (pCR)" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-CDK46TTE26", "trial": null, "papers": [ { "key": "P-CDK46TTE26", "pmid": "42836919", "title": "Target trial emulation of first-line ribociclib versus palbociclib in hormone receptor-positive, HER2-negative metastatic breast cancer: a comparative effectiveness study.", "journal": "Breast Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42836919/", "doi": "10.1007/s12282-026-01921-9", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "This emulates a comparison and is not randomized evidence of superiority. The authors note residual temporal confounding that could favor ribociclib. Requiring another prescription can select people on future exposure; removing that condition and restricting calendar time were not jointly evaluated in the abstract. Propensity matching cannot ensure balance in unmeasured prognosis, treatment access or outcome recording. Safety comparisons were exploratory recorded-event analyses. Full methods, missingness, sensitivity analyses and cohort overlap with other literature remain unreviewed. No TriNetX participant data were accessed.", "by": "Codex (GPT-6)", "added": "2026-10-07", "label": "Ribociclib versus palbociclib: target-trial emulation", "program": "breast", "kind": "observational", "level": "clinical", "result": "positive", "setting": "First-line endocrine combination treatment in a retrospective electronic-health-record comparison", "population": "HR-positive, HER2-negative metastatic breast cancer in TriNetX", "claim": "The prescription-confirmed cohort contained 11,685 patients; 4394 were matched, 2197 per group. Ribociclib was associated with longer overall survival in the whole-period analysis (HR 0.82; 95% CI 0.73-0.92). Separately matched calendar-restricted analysis from 2017 included 1924 per group and attenuated the association to HR 0.90 (95% CI 0.82-0.99). The all-initiator analysis reported HR 0.86 but did not restrict calendar time.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-RSNodes26", "trial": null, "papers": [ { "key": "P-RSNodes26", "pmid": "42836707", "title": "21-Gene recurrence score assay in pN2-3 Early-Stage breast cancer: a national cancer database study.", "journal": "J Natl Cancer Inst", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42836707/", "doi": "10.1093/jnci/djag374", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "The analysis applies to a highly selected tested subgroup and does not validate treatment omission or prove a chemotherapy effect. Testing selection, confounding by indication and residual confounding remain; the authors call for randomized trials. Overall survival does not isolate breast-cancer recurrence. An E-value is a sensitivity descriptor, not evidence that confounding was eliminated. Full methods, treatment-timing alignment, competing risks and overlap with other NCDB cohorts remain unreviewed. No individual registry data were accessed.", "by": "Codex (GPT-6)", "added": "2026-10-07", "label": "Recurrence score in pN2-3: selected National Cancer Database cohort", "program": "breast", "kind": "observational", "level": "clinical", "result": "positive", "setting": "Adjuvant chemotherapy receipt compared retrospectively within a tested registry subset", "population": "HR-positive, HER2-negative early breast cancer with pN2-3 nodal status and recurrence score at most 25", "claim": "Of 50,229 eligible pN2-3 patients, 3,110 (6%) underwent recurrence-score testing. Among tested patients, 2,058 had scores at most 25 and 68% received chemotherapy. With median follow-up of 5.3 years, propensity-score-weighted chemotherapy receipt was associated with longer overall survival (HR 0.62; 95% CI 0.48-0.81; P=0.0002).", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-GCMMA26", "trial": null, "papers": [ { "key": "P-GCMMA26", "pmid": "42839733", "title": "Methylmalonic Acid Induces Oxaliplatin Resistance Through Promoting DNA Damage Repair via the ATM/ATR Pathway in Gastric Cancer.", "journal": "FASEB J", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42839733/", "doi": "10.1096/fj.202600528R", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The functional treatment evidence is preclinical; the human serum finding is an association. The abstract does not report randomized clinical evaluation, therapeutic dosing or clinical safety of vitamin B12 as an antineoplastic intervention. Metabolite perturbation is not demonstrated to cure cancer or reverse resistance in patients. Clinical-sample counts, confounding, model selection, exposure realism, controls and full methods remain unreviewed. These observations do not add RISCON patient records or an executed simulation.", "by": "Codex (GPT-6)", "added": "2026-10-08", "label": "Methylmalonic acid and oxaliplatin resistance in gastric models", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Experimental oxaliplatin exposure and metabolite perturbation", "population": "Gastric cancer cell and in-vivo models, with a serum clinical-sample association", "claim": "Higher serum methylmalonic acid (MMA) was associated with chemoresistance and advanced stage. In experimental gastric models, MMA reduced oxaliplatin-induced DNA damage, increased ATAD5 and activated ATM/ATR-associated homologous-recombination repair. The authors reported impaired oxaliplatin activity in vivo and reversal of MMA-induced resistance after PCCA silencing or vitamin B12 supplementation.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-BMPP826", "trial": null, "papers": [ { "key": "P-BMPP826", "pmid": "42839592", "title": "MPP8 Facilitates DNA DSB Repair via NHEJ to Promote Chemoresistance of TNBC Independent of Methyl-H3K9 Binding.", "journal": "Adv Sci (Weinh)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42839592/", "doi": "10.1002/advs.78157", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "Genetic depletion in cells and mouse models is not a clinically tested selective inhibitor or treatment strategy. Increased cleaved PARP1 is an apoptosis readout, not evidence of PARP-inhibitor sensitivity or a PARP1 therapeutic dependency. Patient efficacy, survival, delivery, selectivity and normal-tissue safety are not established. Full methods, rescue controls and independence of experimental replications remain unreviewed.", "by": "Codex (GPT-6)", "added": "2026-10-08", "label": "MPP8-dependent repair and doxorubicin resistance in TNBC models", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Doxorubicin or irradiation in cells; doxorubicin in orthotopic xenografts", "population": "Triple-negative breast cancer cells and murine orthotopic xenograft models", "claim": "MPP8 depletion reduced clonogenic survival after doxorubicin or irradiation and delayed DNA-damage repair and gamma-H2AX clearance. The study linked MPP8 to the DNA-PK complex and recruitment of the ligase apparatus for non-homologous end joining, separately from methyl-H3K9 binding. MPP8 knockdown resensitized orthotopic TNBC xenografts to doxorubicin.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-GCGULP126", "trial": null, "papers": [ { "key": "P-GCGULP126", "pmid": "42840204", "title": "GULP1 Fuels Resistance to PD-1 Blockade through Lipid-Mediated Metabolic Reprogramming of Tumor-Associated Macrophages in Gastric Cancer.", "journal": "Cancer Commun (Lond)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42840204/", "doi": "10.34133/cancomm.0054", "errata": [] } ], "pages": [], "targets": [ "PDCD1", "CD274" ], "biomarkers": [], "subtypes": [], "limits": "Human expression associations, tumor-cell lipid production and macrophage phenotypes are separate observations. This does not establish a clinically validated predictive cutoff, treatment interaction, a tumor-cell PD-L1 staining score or clinical benefit from glycyrrhizic acid. Pharmacologic selectivity, genetic rescue, exposure, immune-model compatibility and safety require full-method review. No patient treatment, new single-cell analysis or simulation was performed by RISCON.", "by": "Codex (GPT-6)", "added": "2026-10-08", "label": "GULP1-linked lipid remodeling and PD-1 resistance in gastric models", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "Patient transcriptomic association combined with functional cell and tumor-model experiments", "population": "Anti-PD-1-responsive and resistant gastric specimens, public single-cell data and experimental tumor models", "claim": "Elevated GULP1 expression was associated with worse prognosis and poorer responses to PD-1 blockade. Experimental work linked GULP1 to a lipid-enriched tumor environment, accumulation of CD36-positive PD-L1-positive macrophages and impaired CD8 T-cell function. The proposed pathway involved zDHHC8 recruitment, INSIG2 palmitoylation and SREBP1 nuclear translocation; glycyrrhizic acid restored anti-PD-1 sensitivity in vivo in the reported models.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-FANCMAdapt26", "trial": null, "papers": [ { "key": "P-FANCMAdapt26", "pmid": "42838053", "title": "A genome-scale adaptation map identifies the FANCM-RMI1/2 complex as an opposing modulator of cell fitness upon BRCA1 or BRCA2 loss.", "journal": "Mol Cell", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42838053/", "doi": "10.1016/j.molcel.2026.09.017", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Opposing effects are conditional on the experimental genetic states; acute engineered depletion may differ from established tumors. The patient variant association is not a population-level predictive validation or proof of causation. FANCM inhibition is not shown to benefit both mutation groups, and no clinically tested selective intervention or cure is established. Germline status is not specified in this abstract, so the existing germline-BRCA biomarker is not assigned. Full controls, model backgrounds, exposure and clinical chronology remain unreviewed.", "by": "Codex (GPT-6)", "added": "2026-10-08", "label": "Opposing FANCM-RMI1/2 effects after BRCA1 or BRCA2 loss", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "mixed", "setting": "Isogenic acute-depletion genetic-interaction screening and replication-fork experiments", "population": "Engineered BRCA1- or BRCA2-deficient cells; a BRCA2-mutant breast-cancer patient variant observation", "claim": "FANCM was essential in BRCA1-deficient cells but promoted fork degradation and PARP-inhibitor sensitivity in BRCA2-deficient cells through RMI1/2 recruitment. FANCM loss restored fork integrity and alleviated proliferation defects after BRCA2 loss without restoring homologous recombination or eliminating single-stranded DNA gaps. The authors also described a FANCM variant disrupting RMI1/2 binding in a BRCA2-mutant breast-cancer patient associated with PARP-inhibitor resistance.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-GDSCOxali26", "trial": null, "papers": [ { "key": "P-GDSCOxali26", "pmid": "42841136", "title": "Metabolic programs associated with GDSC2-inferred oxaliplatin sensitivity are favorably prognostic in gastric cancer: transcriptomic and single-cell evidence.", "journal": "Front Genet", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42841136/", "doi": "10.3389/fgene.2026.1947421", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "This is an external computational report, not a RISCON execution or independent reproduction. Official NCBI PMC full-text Methods, Discussion and data availability were reviewed: the authors describe a pan-cancer cell-line model transferred from microarray expression to tumor RNA-seq values without cross-platform calibration, and explicitly state that none of their cohorts carry clinical oxaliplatin-response labels. Downstream analysis of expression-defined predicted groups is not independent drug-response validation; prognostic associations and limited mRNA changes do not establish patient efficacy. Source code, implemented preprocessing/splits, tuning isolation, raw data reproduction and clinically annotated treated-cohort validation remain unreviewed or unavailable in this assessment. No participant data were accessed or added to coverage.", "by": "Codex (GPT-6)", "added": "2026-10-08", "label": "GDSC2-inferred oxaliplatin response and gastric metabolic programs", "program": "gastric", "kind": "genomics", "level": "computational", "result": "descriptive", "setting": "External published cell-line-to-tumor expression-model transfer with limited mRNA corroboration", "population": "396 GDSC2 cell lines, 412 TCGA-STAD primary tumors and separate expression/single-cell datasets", "claim": "A ridge model trained on GDSC2 cell lines showed a cross-validated correlation between inferred and observed oxaliplatin AAC of Pearson r=0.50 and Spearman rho=0.44. When the model was applied to TCGA-STAD, predicted AAC quartiles defined resistant-like and sensitive-like groups. Glycolysis discriminated these inferred groups with an AUC of 0.77, but the associated metabolic programs were linked to favorable or neutral prognosis in separate cohorts. AGS cells exposed to the drug showed changes in selected mRNAs; clinical oxaliplatin response was not validated.", "updated": "2026-10-09", "updatedBy": "Codex (GPT-6)", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-TDM1Liver26", "trial": null, "papers": [ { "key": "P-TDM1Liver26", "pmid": "42845032", "title": "Incidence and Risk Factors for Development of Portal Hypertension and Sinusoidal Liver Injury Associated with T-DM1 in HER2-Positive Breast Cancer.", "journal": "Cancer Res Treat", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42845032/", "doi": "10.4143/crt.2025.1385", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "This selected treated cohort has no untreated or alternative-drug comparator, so it does not estimate causal excess risk or individual absolute risk. The composite includes imaging and clinical findings and is not uniformly biopsy-confirmed injury. Adjuvant and palliative populations and exposure durations differ; pooled incidence is not transferable across settings or to another ADC. The authors warn that cumulative-dose association likely reflects prolonged exposure, while the baseline-low-platelet association arose from a very small subgroup. Time-at-risk, competing events, outcome ascertainment, denominator selection and full methods remain unreviewed. No participants were newly accessed by RISCON.", "by": "Codex (GPT-6)", "added": "2026-10-09", "label": "T-DM1-associated portal hypertension and sinusoidal liver injury", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Retrospective adjuvant and palliative T-DM1 exposure, analyzed together", "population": "HER2-positive breast cancer patients treated with T-DM1", "claim": "In 173 retrospectively enrolled patients, the defined portal-hypertension/sinusoidal-liver-injury composite occurred in 31 (17.9%): 11.3% in the adjuvant group and 21.6% in the palliative group. Liver-related T-DM1 discontinuation occurred in 8 cases (4.6%) and significant liver-related complications in 5 (2.9%). The composite combined splenomegaly with other portal-hypertension findings or biopsy-confirmed sinusoidal obstruction syndrome.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-MLH1Punctate26", "trial": null, "papers": [ { "key": "P-MLH1Punctate26", "pmid": "42847237", "title": "Punctate Nuclear MLH1 Staining With the VENTANA M1 Clone in Colorectal Carcinoma: Identification of 3 Patterns in Matched Biopsy-Resection Specimens.", "journal": "Appl Immunohistochem Mol Morphol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42847237/", "doi": "10.1097/PAI.0000000000001348", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-MSI-C" ], "subtypes": [], "limits": "This selected pathology series is not an unselected diagnostic-accuracy study or an immune-treatment trial. A clone-specific staining pitfall cannot be generalized to every antibody, fixation protocol, specimen or staining pattern. IHC protein loss, molecular MSI status, Lynch syndrome diagnosis and clinical response are distinct assessments; no treatment efficacy or causal prediction is established here. Full selection methods, blinding, control staining, reproducibility and orthogonal molecular testing remain unreviewed. The research library does not classify an individual specimen.", "by": "Codex (GPT-6)", "added": "2026-10-09", "label": "Punctate MLH1 staining with the VENTANA M1 clone in colorectal specimens", "program": "colorectal", "kind": "method", "level": "clinical", "result": "descriptive", "setting": "Matched biopsy-resection pathology assessment with an alternative antibody clone", "population": "Selected colorectal carcinoma biopsy-resection pairs, including MLH1/PMS2-deficient cases", "claim": "The study evaluated 24 paired colorectal biopsy-resection cases, including 11 MLH1/PMS2-deficient cases in which the biopsy showed punctate MLH1 staining with the VENTANA M1 clone. Repeat staining with the BioCare G168-15 clone supported interpreting this punctate pattern as MLH1 loss. Four cases were initially misinterpreted by the original pathologists.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ERLowOmission26", "trial": null, "papers": [ { "key": "P-ERLowOmission26", "pmid": "42853497", "title": "Endocrine Therapy Omission in Estrogen Receptor-Low (1-10%) Early Stage Breast Cancer: An Updated Analysis of the NCDB Database.", "journal": "Ann Surg Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42853497/", "doi": "10.1245/s10434-026-20714-0", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [], "limits": "This is an adjusted observational association, not randomized evidence of the causal benefit of starting or omitting endocrine therapy. The expanded calendar window overlaps the earlier NCDB cohort and is not an independent replication. Exposure timing and coding, immortal time, treatment selection, access/adherence, missing data and sensitivity analyses require full-method review. The saved abstract does not provide confidence intervals or a residual-disease interaction test; a subgroup association does not prove a differential treatment effect. ER-low status does not establish HER2-negative or triple-negative disease. No participants were newly accessed by RISCON, and this record does not recommend treatment or omission for an individual.", "by": "Codex (GPT-6)", "added": "2026-10-10", "label": "Expanded NCDB endocrine-therapy omission analysis in ER-low early breast cancer", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Registry association after neoadjuvant and/or adjuvant chemotherapy; overlapping update rather than independent replication", "population": "Stage I–III women with ER-low (1–10%) breast cancer; HER2 distribution is not provided in the saved abstract", "claim": "An expanded NCDB cohort included 12,983 chemotherapy-treated patients diagnosed in 2018–2023; the survival analysis included 11,136 patients diagnosed through 2022. At median follow-up of 3.4 years with 1137 deaths, endocrine-therapy omission was associated with worse overall survival (adjusted HR 1.24, p < 0.001). In patients with residual disease after neoadjuvant chemotherapy, the reported adjusted HR was 1.23 (p = 0.01). The report updates an earlier NCDB cohort from 2018–2020.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-SUV39H2Splice26", "trial": null, "papers": [ { "key": "P-SUV39H2Splice26", "pmid": "42853938", "title": "Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.", "journal": "Sci Adv", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42853938/", "doi": "10.1126/sciadv.aea2001", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [], "limits": "The received abstract reports cell-based perturbation and a prognostic association, not clinical response to a splicing intervention or a validated patient-selection marker. Reducing total SUV39H2 expression/activity with a gapmer or inhibitor is not by itself proof of an exon-specific therapeutic effect. Selectivity, splice-isoform controls, genetic rescue, dose/exposure, normal-tissue toxicity and durable tumor control require full-method review. Senescence and its secretory program do not establish tumor eradication or cure. Prognosis does not validate a treatment-response interaction. The abstract does not establish the patient cohort treatment context or HER2 status, so no ESR1-mutation or HR-positive/HER2-negative subtype is assigned. RISCON did not execute or reproduce these experiments.", "by": "Codex (GPT-6)", "added": "2026-10-10", "label": "SUV39H2 splicing and CDK4/6-inhibitor resistance in breast cancer cells", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "Resistant-cell perturbation and separate patient prognostic correlation", "population": "CDK4/6-inhibitor-resistant breast cancer cells and a breast-cancer prognostic association described in the abstract", "claim": "The authors link increased inclusion of SUV39H2 exon 2 to SUV39H2 overexpression in CDK4/6-inhibitor-resistant breast cancer cells. Gapmer antisense oligonucleotides or a methyltransferase inhibitor targeting SUV39H2 were reported to reverse resistance and restore treatment-induced senescence by reducing its expression or activity. The proposed mechanism links removal of H3K9me3 to chromatin accessibility and p21 transcription. A separate patient association links greater exon inclusion with poorer prognosis.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CodeBreaK300", "trial": "C-CODEBREAK300", "papers": [ { "key": "P-CodeBreaK300", "pmid": "37870968", "title": "Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37870968/", "doi": "10.1056/NEJMoa2308795", "errata": [ { "pmid": "39938112", "title": "Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C.", "url": "https://pubmed.ncbi.nlm.nih.gov/39938112/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [ { "key": "codebreak300-correction-2025", "title": "CodeBreaK 300 — journal correction of the abstract values (N Engl J Med 2025;392:728)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx240006", "file": "data/sources/pages/codebreak300-correction-2025.txt" } ], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label with small groups and short follow-up; overall survival data were still maturing in this report, so a survival benefit is not shown here. Progression-free survival was the primary end point. The PubMed abstract still shows the original values; the correction notice was read, the corrected full article was not. The response and adverse-event figures are from the abstract and the notice does not say whether they changed. The comparison is with late-line standard care, not with a KRAS G12C inhibitor alone or with adagrasib plus cetuximab. KRAS G12C is found in a small minority of metastatic colorectal cancers and the result does not extend to other RAS mutations. KRAS and EGFR are not atlas targets, so no target is linked.", "label": "CodeBreaK 300 · sotorasib plus panitumumab in KRAS G12C colorectal cancer", "kind": "rct", "result": "positive", "setting": "Chemorefractory metastatic disease; phase 3, multicenter, open-label, randomized comparison with investigator's choice of trifluridine-tipiracil or regorafenib", "population": "Metastatic colorectal cancer with mutated KRAS G12C, no previous KRAS G12C inhibitor", "claim": "Patients were assigned to sotorasib 960 mg once daily plus panitumumab (53 patients), sotorasib 240 mg once daily plus panitumumab (53 patients) or standard care (54 patients). The figures below are from the journal's correction published February 12, 2025, which replaced the original values in the abstract after a reanalysis using the same data cutoff. After a median follow-up of 7.8 months, median progression-free survival by blinded independent central review was 5.6 months (95% CI 4.2 to 6.3), 3.9 months (95% CI 3.6 to 5.7) and 2.0 months (95% CI 1.9 to 3.9), respectively. The hazard ratio for progression or death versus standard care was 0.48 (95% CI 0.30 to 0.78; P=0.005) for the 960-mg group and 0.59 (95% CI 0.37 to 0.95; P=0.036) for the 240-mg group; the corrected conclusion attributes significantly longer progression-free survival to the 960-mg dose only. Objective response rates were 26.4%, 5.7% and 0%, respectively, and treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2% and 43.1%; these figures are as reported in the abstract.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-CODEBREAK300", "nct": "NCT05198934", "acronym": "CodeBreak300", "title": "Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 160, "sponsor": "Amgen", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2022-04-19", "lastUpdate": "2026-07-22", "url": "https://clinicaltrials.gov/study/NCT05198934" }, "sources": 3, "corrections": 1, "analysisRecord": null }, { "id": "U-KRYSTAL1CRC", "trial": "C-KRYSTAL1", "papers": [ { "key": "P-KRYSTAL1CRC", "pmid": "36546659", "title": "Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C.", "journal": "N Engl J Med", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/36546659/", "doi": "10.1056/NEJMoa2212419", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Nonrandomized cohorts; the monotherapy and combination groups were not assigned by chance, so the difference in response between them is not a comparative effect. Small evaluable numbers and wide intervals. No comparison with standard care and no overall survival result in the abstract. Not to be pooled with the randomized sotorasib-panitumumab trial as if both were one estimate. KRAS and EGFR are not atlas targets, so no target is linked.", "label": "KRYSTAL-1 · adagrasib with or without cetuximab in KRAS G12C colorectal cancer", "kind": "single-arm", "result": "positive", "setting": "Heavily pretreated metastatic disease; phase 1-2, open-label, nonrandomized cohorts of adagrasib 600 mg twice daily alone or with cetuximab", "population": "Metastatic colorectal cancer with mutant KRAS G12C", "claim": "As of June 16, 2022, 44 patients had received adagrasib and 32 had received adagrasib with cetuximab, with a median follow-up of 20.1 and 17.5 months, respectively. With monotherapy (43 evaluable patients) a response was reported in 19% (95% CI 8 to 33), median response duration was 4.3 months and median progression-free survival was 5.6 months (95% CI 4.1 to 8.3). With the combination (28 evaluable patients) response was 46% (95% CI 28 to 66), median response duration 7.6 months and median progression-free survival 6.9 months (95% CI 5.4 to 8.1). Grade 3 or 4 treatment-related adverse events occurred in 34% with monotherapy and 16% with the combination; no grade 5 adverse events were observed.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-KRYSTAL1", "nct": "NCT03785249", "acronym": null, "title": "Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE1", "PHASE2" ], "enrollment": 731, "sponsor": "Mirati Therapeutics Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2019-01-15", "lastUpdate": "2026-07-29", "url": "https://clinicaltrials.gov/study/NCT03785249" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-FRESCO2", "trial": "C-FRESCO2", "papers": [ { "key": "P-FRESCO2", "pmid": "37331369", "title": "Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study.", "journal": "Lancet", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37331369/", "doi": "10.1016/S0140-6736(23)00772-9", "errata": [] } ], "pages": [], "targets": [ "KDR" ], "biomarkers": [], "subtypes": [], "limits": "Placebo-controlled in a last-line population; it does not compare fruquintinib with trifluridine-tipiracil, regorafenib or combinations. The absolute gain in median survival was a few months and median survival stayed under one year in both groups. Quality-of-life analysis was not reported in this abstract. The result says nothing about earlier lines of treatment.", "label": "FRESCO-2 · fruquintinib versus placebo in refractory colorectal cancer", "kind": "rct", "result": "positive", "setting": "Refractory metastatic disease after all standard cytotoxic and targeted therapies and progression on or intolerance to trifluridine-tipiracil or regorafenib, or both; international, double-blind, placebo-controlled phase 3 study", "population": "Adults with metastatic colorectal adenocarcinoma; a median of 4 previous lines of systemic therapy for metastatic disease", "claim": "Between Aug 12, 2020, and Dec 2, 2021, 691 patients were randomly assigned 2:1 to fruquintinib (n=461) or placebo (n=230) plus best supportive care; 502 (73%) of 691 had received more than 3 previous lines. Median overall survival was 7.4 months (95% CI 6.7-8.2) with fruquintinib versus 4.8 months (4.0-5.8) with placebo (hazard ratio 0.66, 95% CI 0.55-0.80; p<0.0001). Grade 3 or worse adverse events occurred in 286 (63%) of 456 patients who received fruquintinib and 116 (50%) of 230 who received placebo, most often hypertension (14%), asthenia (8%) and hand-foot syndrome (6%) with fruquintinib. There was one treatment-related death in each group.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-FRESCO2", "nct": "NCT04322539", "acronym": "FRESCO-2", "title": "A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 691, "sponsor": "Hutchison Medipharma Limited", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2020-08-12", "lastUpdate": "2025-04-04", "url": "https://clinicaltrials.gov/study/NCT04322539" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-RECOURSE", "trial": "C-RECOURSE", "papers": [ { "key": "P-RECOURSE", "pmid": "25970050", "title": "Randomized trial of TAS-102 for refractory metastatic colorectal cancer.", "journal": "N Engl J Med", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25970050/", "doi": "10.1056/NEJMoa1414325", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Placebo-controlled in a refractory population; the absolute gain in median survival was under two months and median survival stayed under one year. The abstract does not give the numbers per group or results by RAS status. This trial is the single-agent reference for the later comparison of the same drug with and without bevacizumab; the two trials enrolled different populations and their medians should not be compared directly.", "label": "RECOURSE · TAS-102 versus placebo in refractory colorectal cancer", "kind": "rct", "result": "positive", "setting": "Refractory metastatic disease; double-blind phase 3 trial, assigned in a 2:1 ratio", "population": "800 patients with refractory colorectal cancer in a global population", "claim": "Median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102 (hazard ratio for death 0.68; 95% CI 0.58 to 0.81; P<0.001). Median time to worsening performance status was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio 0.66; 95% CI 0.56 to 0.78; P<0.001). Neutropenia occurred in 38% and leukopenia in 21% of those treated with TAS-102; 4% had febrile neutropenia, and one death related to TAS-102 was reported.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-RECOURSE", "nct": "NCT01607957", "acronym": "RECOURSE", "title": "Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 800, "sponsor": "Taiho Oncology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2012-06-17", "lastUpdate": "2024-09-19", "url": "https://clinicaltrials.gov/study/NCT01607957" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-PARADIGM", "trial": "C-PARADIGM", "papers": [ { "key": "P-PARADIGM", "pmid": "37071094", "title": "Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial.", "journal": "JAMA", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37071094/", "doi": "10.1001/jama.2023.4428", "errata": [ { "pmid": "37367990", "title": "Error in Text Wording and Incorrect Reference.", "url": "https://pubmed.ncbi.nlm.nih.gov/37367990/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label and conducted in Japan only. Overall survival was longer without a difference in progression-free survival, so the survival difference may reflect later treatment or deeper response and its mechanism is not shown. The abstract gives no separate result for right-sided tumors, so it does not show which antibody is better there. Applies to RAS wild-type disease; BRAF status is not reported in the abstract. EGFR is not an atlas target, so no target is linked.", "label": "PARADIGM · panitumumab versus bevacizumab with first-line chemotherapy by tumour side", "kind": "rct", "result": "positive", "setting": "First-line treatment of unresectable metastatic disease with mFOLFOX6; randomized, open-label phase 3 trial at 197 sites in Japan", "population": "823 patients with chemotherapy-naive RAS wild-type metastatic colorectal cancer; in the as-treated population (n = 802), 604 (75.3%) had left-sided tumors", "claim": "Patients received panitumumab (n = 411) or bevacizumab (n = 412) plus mFOLFOX6; median follow-up was 61 months. In participants with left-sided tumors, median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab (HR for death 0.82; 95.798% CI 0.68-0.99; P = .03); in the overall population it was 36.2 vs 31.3 months (HR 0.84; 95% CI 0.72-0.98; P = .03). Median progression-free survival in left-sided tumors was 13.1 vs 11.9 months (HR 1.00; 95% CI 0.83-1.20). Response rates were 80.2% vs 68.6% and curative resection rates 18.3% vs 11.6% for left-sided tumors. Acneiform rash occurred in 74.8% with panitumumab and 3.2% with bevacizumab.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-PARADIGM", "nct": "NCT02394795", "acronym": "PARADIGM", "title": "Panitumumab and RAS, Diagnostically-useful Gene Mutation for mCRC", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 823, "sponsor": "Takeda", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-05-29", "lastUpdate": "2023-11-01", "url": "https://clinicaltrials.gov/study/NCT02394795" }, "sources": 2, "corrections": 1, "analysisRecord": null }, { "id": "U-BREAKWATER", "trial": "C-BREAKWATER", "papers": [ { "key": "P-BREAKWATER25", "pmid": "40444708", "title": "Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40444708/", "doi": "10.1056/NEJMoa2501912", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Open-label; the overall survival result comes from an interim analysis and may change with longer follow-up. The abstract does not report results for encorafenib plus cetuximab without chemotherapy, numbers per group, or results by microsatellite status. Applies to BRAF V600E only, not other BRAF alterations. Separate from the earlier trial of the same targeted pair in previously treated disease; the two populations differ. BRAF and EGFR are not atlas targets, so no target is linked.", "label": "BREAKWATER · first-line encorafenib, cetuximab and mFOLFOX6 in BRAF V600E colorectal cancer", "kind": "rct", "result": "positive", "setting": "First-line treatment of metastatic disease; open-label phase 3 trial of encorafenib plus cetuximab (EC), EC plus mFOLFOX6, or standard care (chemotherapy with or without bevacizumab)", "population": "Untreated BRAF V600E-mutated metastatic colorectal cancer", "claim": "Progression-free survival by blinded independent central review was longer with EC+mFOLFOX6 than with standard care (median 12.8 vs. 7.1 months; hazard ratio for progression or death 0.53; 95% CI 0.41 to 0.68; P<0.001). In an interim analysis, overall survival was longer with EC+mFOLFOX6 (median 30.3 vs. 15.1 months; hazard ratio for death 0.49; 95% CI 0.38 to 0.63; P<0.001). The earlier primary end point, objective response, had favoured EC+mFOLFOX6 (odds ratio 2.44; one-sided P<0.001). Serious adverse events during treatment occurred in 46.1% with EC+mFOLFOX6 and 38.9% with standard care.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-BREAKWATER", "nct": "NCT04607421", "acronym": null, "title": "A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 841, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [ "Ono Pharmaceutical Co., Ltd.", "Merck KGaA, Darmstadt, Germany", "Eli Lilly and Company" ], "hasResults": true, "start": "2020-12-21", "lastUpdate": "2026-06-11", "url": "https://clinicaltrials.gov/study/NCT04607421" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-ATOMIC", "trial": "C-ATOMIC", "papers": [ { "key": "P-ATOMIC26", "pmid": "41880612", "title": "Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer.", "journal": "N Engl J Med", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41880612/", "doi": "10.1056/NEJMoa2507874", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "Disease-free survival was the primary end point; the abstract reports no overall survival result. Both groups received oxaliplatin-based chemotherapy, so the trial does not test immunotherapy without chemotherapy or a neoadjuvant approach. Grade 3 or 4 adverse events were frequent in both groups and more frequent with atezolizumab. Applies to mismatch repair-deficient stage III colon cancer only, not to proficient tumours, stage II disease or rectal cancer.", "label": "ATOMIC · adjuvant atezolizumab with FOLFOX in stage III dMMR colon cancer", "kind": "rct", "result": "positive", "setting": "Adjuvant treatment after resection; phase 3 trial, assigned in a 1:1 ratio to atezolizumab plus mFOLFOX6 for 6 months then atezolizumab alone (12 months of therapy in total) or mFOLFOX6 alone for 6 months", "population": "Resected stage III mismatch repair-deficient colon cancer; median age 64 years; 53.9% had tumors that were T4, N2, or both", "claim": "A total of 355 patients were assigned to atezolizumab plus mFOLFOX6 and 357 to mFOLFOX6 alone. At a median follow-up of 40.9 months, 3-year disease-free survival was 86.3% (95% CI 81.8 to 89.8) versus 76.2% (95% CI 70.9 to 80.6) (hazard ratio for recurrence or death 0.50; 95% CI 0.35 to 0.73; P<0.001). Adverse events of grade 3 or 4 occurred in 84.1% with atezolizumab plus mFOLFOX6 and 71.9% with mFOLFOX6 alone.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "C-ATOMIC", "nct": "NCT02912559", "acronym": null, "title": "Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 712, "sponsor": "National Cancer Institute (NCI)", "sponsorClass": "NIH", "collaborators": [], "hasResults": true, "start": "2017-10-16", "lastUpdate": "2026-10-28", "url": "https://clinicaltrials.gov/study/NCT02912559" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-IDEA18", "trial": null, "papers": [ { "key": "P-IDEA18", "pmid": "29590544", "title": "Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.", "journal": "N Engl J Med", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29590544/", "doi": "10.1056/NEJMoa1713709", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary noninferiority question was not confirmed; the regimen and risk-group findings are subgroup or exploratory analyses. The choice between FOLFOX and CAPOX was not randomized, so the difference between regimens may reflect which patients and centres chose each. The abstract gives no neurotoxicity figures and no overall survival result. A pooled analysis of six trials is linked here without a single registration.", "label": "IDEA · three versus six months of adjuvant oxaliplatin-based chemotherapy in stage III colon cancer", "kind": "analysis", "result": "mixed", "setting": "Adjuvant FOLFOX or CAPOX for 3 months compared with 6 months; prospective, preplanned, pooled analysis of six randomized phase 3 trials conducted concurrently", "population": "12,834 patients with stage III colon cancer", "claim": "After 3263 recurrence or death events, noninferiority of 3 months versus 6 months was not confirmed in the overall population (hazard ratio 1.07; 95% CI 1.00 to 1.15; noninferiority margin 1.12). Noninferiority was seen for CAPOX (hazard ratio 0.95; 95% CI 0.85 to 1.06) but not for FOLFOX (hazard ratio 1.16; 95% CI 1.06 to 1.26). In an exploratory analysis of T1, T2, or T3 and N1 cancers, 3-year disease-free survival was 83.1% with 3 months and 83.3% with 6 months (hazard ratio 1.01; 95% CI 0.90 to 1.12). Among cancers classified as T4, N2, or both, 6 months was superior (64.4% vs. 62.7%; hazard ratio 1.12; 95% CI 1.03 to 1.23; P=0.01 for superiority).", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-GEMSTONE303", "trial": "G-GEMSTONE303", "papers": [ { "key": "P-GEMSTONE303", "pmid": "39992668", "title": "First-Line Sugemalimab Plus Chemotherapy for Advanced Gastric Cancer: The GEMSTONE-303 Randomized Clinical Trial.", "journal": "JAMA", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39992668/", "doi": "10.1001/jama.2024.28463", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [ "BM-PDL1-CPS" ], "subtypes": [ "G-PDL1" ], "limits": "Only patients with a PD-L1 score of 5 or greater were enrolled, so the trial says nothing about lower scores. All sites were in China. No comparison with other checkpoint antibodies is made.", "label": "GEMSTONE-303 · first-line sugemalimab in PD-L1 CPS ≥5 disease", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line, with capecitabine and oxaliplatin", "population": "Unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 combined positive score of 5 or greater", "claim": "In this double-blind phase 3 trial at 54 sites in China, 479 patients were randomised to the PD-L1 antibody sugemalimab (n = 241) or placebo (n = 238), each with chemotherapy. Median overall survival was 15.6 months (95% CI 13.3-17.8) versus 12.6 months (95% CI 10.6-14.1) (hazard ratio 0.75, 95% CI 0.61-0.92; P = .006), and median progression-free survival 7.6 versus 6.1 months (hazard ratio 0.66, 95% CI 0.54-0.81). Grade 3 or higher treatment-related adverse events occurred in 53.9% versus 50.6%.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "G-GEMSTONE303", "nct": "NCT03802591", "acronym": null, "title": "A Study of CS1001 in Subjects With Gastric Adenocarcinoma or Gastro-Esophageal Junction Adenocarcinoma", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 479, "sponsor": "CStone Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2019-03-28", "lastUpdate": "2023-11-29", "url": "https://clinicaltrials.gov/study/NCT03802591" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival and investigator-assessed progression-free survival (dual primary endpoints)", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 479, "assessment": "investigator", "quote": "GEMSTONE 303 is a phase 3, randomized, double-blind, placebo-controlled study conducted at 54 sites in China … A total of 479 eligible patients … were randomized. … Primary outcomes were overall survival and investigator-assessed progression-free survival." }, "effect": { "measure": "HR", "value": 0.75, "ci_low": 0.61, "ci_high": 0.92, "ci_level": "95%", "p": ".006", "endpoint": "Overall survival", "quote": "The sugemalimab group demonstrated significant improvements in overall survival (median, 15.6 months [95% CI, 13.3-17.8] vs 12.6 months [95% CI, 10.6-14.1]; hazard ratio, 0.75 [95% CI, 0.61-0.92]; P = .006)" }, "landmark": [], "harms": { "grade3plus_experimental_pct": 53.9, "grade3plus_control_pct": 50.6, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 or higher treatment-related adverse events occurred in 53.9% of patients in the sugemalimab group and 50.6% in the placebo group." }, "takeaway_en": "In previously untreated patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 CPS of 5 or greater, adding sugemalimab to CAPOX improved overall survival compared with placebo plus CAPOX (median 15.6 vs 12.6 months; hazard ratio 0.75) and progression-free survival (median 7.6 vs 6.1 months; hazard ratio 0.66). Grade 3 or higher treatment-related adverse events were somewhat more frequent with sugemalimab (53.9% vs 50.6%).", "takeaway_ko": "이전에 치료받지 않은 절제 불가능한 국소 진행성 또는 전이성 위암·위식도접합부 선암 환자 중 PD-L1 CPS 5 이상인 환자에서 CAPOX에 수게말리맙을 추가했을 때, 위약과 CAPOX 병용 대비 전체생존기간이 개선되었고(중앙값 15.6개월 대 12.6개월, 위험비 0.75), 무진행생존기간도 개선되었습니다(중앙값 7.6개월 대 6.1개월, 위험비 0.66). 3등급 이상 치료 관련 이상반응은 수게말리맙군에서 다소 더 흔했습니다(53.9% 대 50.6%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ESOPEC", "trial": "G-ESOPEC", "papers": [ { "key": "P-ESOPEC", "pmid": "39842010", "title": "Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39842010/", "doi": "10.1056/NEJMoa2409408", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The chemoradiotherapy arm received no adjuvant immunotherapy, which later became an option for patients with residual disease after chemoradiotherapy, so the comparison does not include that strategy. Esophageal adenocarcinoma only; no extrapolation to squamous cancer or to stomach tumours. An earlier trial of a similar comparison was stopped for futility with similar survival.", "label": "ESOPEC · perioperative FLOT versus preoperative chemoradiotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Perioperative chemotherapy compared with preoperative chemoradiotherapy, each with surgery", "population": "Resectable esophageal adenocarcinoma, including tumours of the gastroesophageal junction", "claim": "In the phase 3 ESOPEC trial, 221 patients were assigned to perioperative FLOT and 217 to preoperative chemoradiotherapy. With a median follow-up of 55 months, 3-year overall survival was 57.4% (95% CI 50.1 to 64.0) versus 50.7% (95% CI 43.5 to 57.5) (hazard ratio for death 0.70; 95% CI 0.53 to 0.92; P = 0.01), and 3-year progression-free survival 51.6% versus 35.0% (hazard ratio 0.66; 95% CI 0.51 to 0.85). Grade 3 or higher adverse events occurred in 120 of 207 patients (58.0%) versus 98 of 196 (50.0%); mortality at 90 days after surgery was 3.1% versus 5.6%.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "G-ESOPEC", "nct": "NCT02509286", "acronym": "ESOPEC", "title": "Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 438, "sponsor": "University Hospital Schleswig-Holstein", "sponsorClass": "OTHER", "collaborators": [ "Clinical Trials Unit Freiburg", "University of Freiburg", "University of Leipzig", "University of Luebeck", "University of Hamburg-Eppendorf" ], "hasResults": false, "start": "2016-01", "lastUpdate": "2024-05-08", "url": "https://clinicaltrials.gov/study/NCT02509286" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. … we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group." }, "effect": { "measure": "HR", "value": 0.7, "ci_low": 0.53, "ci_high": 0.92, "ci_level": "95%", "p": "0.01", "endpoint": "Overall survival (death)", "quote": "hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P = 0.01" }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 57.4, "control_pct": 50.7, "higher_is_better": true, "experimental_arm": "Perioperative FLOT plus surgery", "control_arm": "Preoperative chemoradiotherapy plus surgery", "quote": "With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group", "difference_pp": 6.7, "nnt": 15, "quote_note": "P-ESOPEC, NEJM 2025, the only paper provided" }, { "endpoint": "Progression-free survival", "timepoint": "3 years", "experimental_pct": 51.6, "control_pct": 35, "higher_is_better": true, "experimental_arm": "Perioperative FLOT plus surgery", "control_arm": "Preoperative chemoradiotherapy plus surgery", "quote": "Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group", "difference_pp": 16.6, "nnt": 7, "quote_note": "P-ESOPEC, NEJM 2025, the only paper provided" } ], "harms": { "grade3plus_experimental_pct": 58, "grade3plus_control_pct": 50, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Treatment-related deaths not reported. Mortality at 90 days after surgery was 3.1% (FLOT) vs 5.6% (preoperative chemoradiotherapy).", "quote": "Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. … Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group." }, "takeaway_en": "In resectable esophageal adenocarcinoma, perioperative FLOT plus surgery was compared with preoperative chemoradiotherapy (41.4 Gy with carboplatin and paclitaxel) plus surgery; 3-year overall survival was 57.4% versus 50.7% (hazard ratio for death 0.70), and 3-year progression-free survival was 51.6% versus 35.0%. Grade 3 or higher adverse events were more frequent with FLOT (58.0% vs 50.0%), while mortality at 90 days after surgery was 3.1% versus 5.6%.", "takeaway_ko": "절제 가능한 식도선암 환자를 대상으로 수술 전후 FLOT 항암화학요법 후 수술과 수술 전 항암화학방사선요법(41.4 Gy, 카보플라틴·파클리탁셀) 후 수술을 비교했습니다. 3년 전체생존율은 57.4% 대 50.7%(사망 위험비 0.70), 3년 무진행생존율은 51.6% 대 35.0%였습니다. 3등급 이상 이상반응은 FLOT군에서 더 많았으나(58.0% 대 50.0%), 수술 후 90일 사망률은 3.1% 대 5.6%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-NeoAEGIS", "trial": "G-NeoAEGIS", "papers": [ { "key": "P-NeoAEGIS", "pmid": "37734399", "title": "Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.", "journal": "Lancet Gastroenterol Hepatol", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37734399/", "doi": "10.1016/S2468-1253(23)00243-1", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Stopped early for futility and because of the pandemic; the trial does not establish equivalence. Most patients in the chemotherapy arm received an older regimen rather than FLOT, which limits comparison with the later trial that found better survival with FLOT. Better pathological response with chemoradiotherapy did not come with better survival.", "label": "Neo-AEGIS · chemoradiotherapy versus perioperative chemotherapy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Preoperative chemoradiotherapy compared with perioperative chemotherapy, each with surgery", "population": "Locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction", "claim": "The trial closed early after the second futility analysis (143 deaths). In the intention-to-treat population of 362 patients (184 perioperative chemotherapy, 178 chemoradiotherapy), at a median follow-up of 38.8 months, median overall survival was 48.0 versus 49.2 months and 3-year overall survival was 55% versus 57% (hazard ratio 1.03, 95% CI 0.77-1.38). Median disease-free survival was 32.4 versus 24.0 months (hazard ratio 0.89, 95% CI 0.68-1.17). Pathological complete response (odds ratio 0.33, 95% CI 0.14-0.81), major pathological response and complete resection rates favoured chemoradiotherapy.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "G-NeoAEGIS", "nct": "NCT01726452", "acronym": null, "title": "NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 377, "sponsor": "Cancer Trials Ireland", "sponsorClass": "NETWORK", "collaborators": [ "Southampton Clinical Trials Unit", "Copenhagen University Hospital, Rigshospitalet", "Centre Hospitalier Régional, Universitaire de Lille" ], "hasResults": false, "start": "2013-01-24", "lastUpdate": "2022-09-30", "url": "https://clinicaltrials.gov/study/NCT01726452" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 377, "assessment": "not stated", "quote": "Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe … Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population … 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths)" }, "effect": { "measure": "HR", "value": 1.03, "ci_low": 0.77, "ci_high": 1.38, "ci_level": "95%", "p": "log-rank p=0·82", "endpoint": "Overall survival (perioperative chemotherapy vs trimodality therapy; direction of HR not explicitly stated in abstract)", "quote": "median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82)" }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 57, "control_pct": 55, "higher_is_better": true, "experimental_arm": "Trimodality therapy (CROSS chemoradiotherapy then surgery)", "control_arm": "Perioperative chemotherapy (modified MAGIC or FLOT) with surgery", "quote": "At a median follow-up of 38·8 months (IQR 16·3-55·1) … (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]", "difference_pp": 2, "nnt": 50 } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Two deaths possibly related to treatment, one in each group. Deaths from serious adverse events: 1 (1%) with perioperative chemotherapy vs 3 (2%) with trimodality therapy.", "quote": "The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group)" }, "takeaway_en": "In patients with locally advanced (cT2-3, N0-3, M0) adenocarcinoma of the oesophagus or oesophagogastric junction, CROSS chemoradiotherapy before surgery and perioperative chemotherapy (mostly modified MAGIC) gave similar 3-year overall survival, 57% versus 55% (hazard ratio 1.03, 95% CI 0.77-1.38). The trial closed early and was underpowered. Chemoradiotherapy produced more pathological complete responses and R0 resections, while perioperative chemotherapy caused more grade 3-4 neutropenia (27% vs 6%) and diarrhoea (11% vs none), with similar operative mortality.", "takeaway_ko": "국소 진행성(cT2-3, N0-3, M0) 식도 및 식도위접합부 선암 환자에서 수술 전 CROSS 항암화학방사선요법과 수술 전후 항암화학요법(주로 변형 MAGIC)의 3년 전체생존율은 57%와 55%로 비슷했습니다(위험비 1.03, 95% 신뢰구간 0.77-1.38). 이 시험은 조기 종료되어 검정력이 부족했습니다. 항암화학방사선요법군에서 병리학적 완전관해율과 R0 절제율이 더 높았고, 수술 전후 항암화학요법군에서는 3-4등급 호중구감소증(27% 대 6%)과 설사(11% 대 0명)가 더 많았으며, 수술 관련 사망률은 비슷했습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-EXPEL", "trial": "G-EXPEL", "papers": [ { "key": "P-EXPEL", "pmid": "33253659", "title": "Extensive peritoneal lavage with saline after curative gastrectomy for gastric cancer (EXPEL): a multicentre randomised controlled trial.", "journal": "Lancet Gastroenterol Hepatol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33253659/", "doi": "10.1016/S2468-1253(20)30315-0", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A negative trial of a surgical measure meant to reduce peritoneal recurrence; it does not test intraperitoneal chemotherapy. Follow-up was short for late recurrence. The imbalance in fatal adverse events is based on ten events.", "label": "EXPEL · extensive peritoneal lavage after gastrectomy", "program": "gastric", "kind": "rct", "level": "clinical", "result": "negative", "setting": "Curative gastrectomy with or without extensive intraoperative peritoneal lavage", "population": "Gastric cancer treated with curative-intent gastrectomy", "claim": "In the EXPEL trial, 800 patients were assigned to surgery with extensive lavage (n=398) or standard surgery (n=402). The trial was stopped for futility at the third interim analysis. With a median follow-up of 2.4 years, overall survival was similar (hazard ratio 1.09, 95% CI 0.78-1.52; p=0.62); 3-year overall survival was 77.0% versus 76.7%. Sixty adverse events were reported with lavage and 41 with standard surgery, and ten reported events resulted in death (eight versus two).", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "G-EXPEL", "nct": "NCT02140034", "acronym": "EPL", "title": "Extensive Peritoneal Lavage After Curative Gastrectomy for Gastric Cancer: A Randomised Controlled Trial", "status": "UNKNOWN", "phases": [ "NA" ], "enrollment": 600, "sponsor": "National University Hospital, Singapore", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2013-05", "lastUpdate": "2014-05-16", "url": "https://clinicaltrials.gov/study/NCT02140034" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Overall survival", "primary_endpoint_type": "OS", "design": { "phase": "3", "randomized": true, "blinding": "open-label", "n_randomized": 800, "assessment": "not stated", "quote": "In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres … 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402)." }, "effect": { "measure": "HR", "value": 1.09, "ci_low": 0.78, "ci_high": 1.52, "ci_level": "95%", "p": "0·62", "endpoint": "Overall survival", "quote": "With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62)." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "3 years", "experimental_pct": 77, "control_pct": 76.7, "higher_is_better": true, "experimental_arm": "Surgery plus extensive intraoperative peritoneal lavage (EIPL)", "control_arm": "Standard surgery alone", "quote": "3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group.", "difference_pp": 0.3, "nnt": 334, "quote_note": "single paper, PMID 33253659, median follow-up 2·4 years" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "Ten reported adverse events resulted in death: eight in the EIPL group and two in the standard surgery group. Attribution to treatment is not stated.", "quote": "60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. … Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death." }, "takeaway_en": "In patients with cT3 or cT4 gastric cancer undergoing curative gastrectomy, adding extensive intraoperative peritoneal lavage did not improve survival compared with surgery alone. The trial was stopped for futility, and 3-year overall survival was 77.0% with lavage versus 76.7% without (HR 1.09). The lavage group had more reported adverse events (60 vs 41) and more adverse events that resulted in death (eight vs two).", "takeaway_ko": "근치적 위절제술을 받는 cT3 또는 cT4 위암 환자에서 수술 중 광범위 복강 세척을 추가해도 수술 단독군보다 생존이 개선되지 않았으며, 시험은 무익성으로 조기 종료되었습니다. 3년 전체생존율은 세척군 77.0%, 수술 단독군 76.7%였습니다(위험비 1.09). 세척군에서 보고된 이상반응이 더 많았고(60건 대 41건), 사망으로 이어진 이상반응도 더 많았습니다(8건 대 2건).", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ML3", "trial": "B-ML3", "papers": [ { "key": "P-ML3", "pmid": "29860922", "title": "Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.", "journal": "J Clin Oncol", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/29860922/", "doi": "10.1200/JCO.2018.78.9909", "errata": [] }, { "key": "P-ML3OS", "pmid": "31826360", "title": "Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/31826360/", "doi": "10.1056/NEJMoa1911149", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Results for ribociclib are not evidence about other CDK4/6 inhibitors, and no cross-trial comparison is made. The population mixes first-line and second-line patients. Both abstracts are one trial.", "label": "MONALEESA-3 · ribociclib plus fulvestrant", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line or after up to one line of endocrine therapy for advanced disease", "population": "Postmenopausal women and men with HR-positive, HER2-negative advanced breast cancer", "claim": "In the phase 3 MONALEESA-3 trial, 484 patients were assigned to ribociclib plus fulvestrant and 242 to placebo plus fulvestrant. Median progression-free survival was 20.5 versus 12.8 months (hazard ratio 0.593; 95% CI 0.480 to 0.732). Grade 3 neutropenia occurred in 46.6% versus 0%. In the overall survival analysis based on 275 deaths, 167 of 484 patients (34.5%) versus 108 of 242 (44.6%) had died; estimated overall survival at 42 months was 57.8% versus 45.9% (hazard ratio 0.72; 95% CI 0.57 to 0.92; P = 0.00455).", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "B-ML3", "nct": "NCT02422615", "acronym": "MONALEESA-3", "title": "Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 726, "sponsor": "Novartis Pharmaceuticals", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2015-06-09", "lastUpdate": "2023-11-30", "url": "https://clinicaltrials.gov/study/NCT02422615" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Locally assessed progression-free survival", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "investigator", "quote": "This phase III study evaluated ribociclib plus fulvestrant … Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival … A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant." }, "effect": { "measure": "HR", "value": 0.593, "ci_low": 0.48, "ci_high": 0.732, "ci_level": "95%", "p": "P < .001", "endpoint": "Progression-free survival (primary, locally assessed)", "quote": "Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001)." }, "landmark": [ { "endpoint": "Overall survival", "timepoint": "42 months", "experimental_pct": 57.8, "control_pct": 45.9, "higher_is_better": true, "experimental_arm": "Ribociclib plus fulvestrant", "control_arm": "Placebo plus fulvestrant", "quote": "The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group", "difference_pp": 11.9, "nnt": 9, "quote_note": "NEJM 2020 second interim OS analysis" }, { "endpoint": "Overall response rate (patients with measurable disease)", "timepoint": "Primary PFS analysis", "experimental_pct": 40.9, "control_pct": 28.7, "higher_is_better": true, "experimental_arm": "Ribociclib plus fulvestrant", "control_arm": "Placebo plus fulvestrant", "quote": "Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant.", "difference_pp": 12.2, "nnt": 9, "quote_note": "JCO 2018 primary analysis" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%)." }, "takeaway_en": "In postmenopausal patients with HR-positive, HER2-negative advanced breast cancer receiving first- or second-line fulvestrant, adding ribociclib improved median progression-free survival from 12.8 to 20.5 months (hazard ratio 0.593), and estimated 42-month overall survival was 57.8% versus 45.9% with placebo. The main trade-off was myelosuppression: grade 3 neutropenia occurred in 46.6% versus 0%, and grade 3 leukopenia occurred in 13.5% versus 0%.", "takeaway_ko": "1차 또는 2차 치료로 풀베스트란트를 투여받는 HR 양성, HER2 음성 진행성 유방암 폐경 후 환자에서 리보시클립을 추가하자 무진행 생존기간 중앙값이 12.8개월에서 20.5개월로 개선되었습니다(위험비 0.593). 42개월 추정 전체 생존율은 위약군 45.9% 대비 57.8%였습니다. 주요 대가는 골수억제로, 3등급 호중구감소증이 46.6% 대 0%, 3등급 백혈구감소증이 13.5% 대 0%에서 발생했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-PALOMA2", "trial": "B-PALOMA2", "papers": [ { "key": "P-PALOMA2", "pmid": "27959613", "title": "Palbociclib and Letrozole in Advanced Breast Cancer.", "journal": "N Engl J Med", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27959613/", "doi": "10.1056/NEJMoa1607303", "errata": [] }, { "key": "P-PALOMA2OS", "pmid": "38252901", "title": "Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38252901/", "doi": "10.1200/JCO.23.00137", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Progression-free survival was the primary end point and was met; overall survival, a secondary end point, was not improved. More patients in the placebo arm had unknown survival status, which the authors say limits interpretation. Two other inhibitors of the same class reported a survival benefit in first-line trials; no cross-trial comparison is made here. Both abstracts are one trial.", "label": "PALOMA-2 · first-line palbociclib plus letrozole", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "First line for advanced disease, with letrozole", "population": "Postmenopausal women with ER-positive, HER2-negative advanced breast cancer and no previous systemic therapy for advanced disease", "claim": "In the phase 3 PALOMA-2 trial (N = 666), median progression-free survival was 24.8 versus 14.5 months (hazard ratio 0.58; 95% CI 0.46 to 0.72; P<0.001), with grade 3 or 4 neutropenia in 66.4% versus 1.4%. After a median follow-up of 90.1 months and 405 deaths, median overall survival was 53.9 versus 51.2 months (HR 0.96, 95% CI 0.78 to 1.18; stratified one-sided P = .34). Survival status was unknown for 13.3% versus 21.2% of patients; with recovered data the hazard ratio was 0.92 (95% CI 0.76 to 1.12). Overall survival was not significantly improved.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "B-PALOMA2", "nct": "NCT01740427", "acronym": null, "title": "A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 666, "sponsor": "Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2013-02-22", "lastUpdate": "2024-11-14", "url": "https://clinicaltrials.gov/study/NCT01740427" }, "sources": 3, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival, as assessed by the investigators", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 666, "assessment": "investigator", "quote": "In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators" }, "effect": { "measure": "HR", "value": 0.58, "ci_low": 0.46, "ci_high": 0.72, "ci_level": "95%", "p": "P<0.001", "endpoint": "Progression-free survival (disease progression or death)", "quote": "The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": 9.7, "discontinuation_control_pct": 5.9, "treatment_related_deaths": null, "quote": "The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group." }, "takeaway_en": "In 666 postmenopausal women with ER-positive, HER2-negative advanced breast cancer and no prior treatment for advanced disease, palbociclib plus letrozole was compared with placebo plus letrozole. Median progression-free survival was 24.8 versus 14.5 months (hazard ratio 0.58), but overall survival was not significantly improved (hazard ratio 0.96). The main trade-off was myelotoxicity: grade 3 or 4 neutropenia occurred in 66.4% versus 1.4% of patients, and adverse events led to permanent treatment discontinuation in 9.7% versus 5.9%.", "takeaway_ko": "진행성 질환에 대한 치료 경험이 없는 폐경 후 ER 양성, HER2 음성 진행성 유방암 환자 666명을 대상으로 팔보시클립+레트로졸과 위약+레트로졸을 비교했습니다. 무진행생존기간 중앙값은 24.8개월 대 14.5개월(위험비 0.58)이었으나, 전체생존기간은 유의하게 개선되지 않았습니다(위험비 0.96). 주요 위해는 골수독성으로, 3–4등급 호중구감소증이 66.4% 대 1.4%에서 발생했고, 이상반응으로 인한 치료 영구 중단은 9.7% 대 5.9%였습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-NALA", "trial": "B-NALA", "papers": [ { "key": "P-NALA", "pmid": "32678716", "title": "Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.", "journal": "J Clin Oncol", "year": "2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32678716/", "doi": "10.1200/JCO.20.00147", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The trial had two coprimary end points with split alpha and was declared positive on progression-free survival; overall survival was not significantly different. The comparator is an older tyrosine kinase inhibitor regimen, not an antibody-drug conjugate. The brain-disease finding is a secondary end point with a P value close to .05.", "label": "NALA · neratinib versus lapatinib, each with capecitabine", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Third line or later for metastatic disease", "population": "HER2-positive metastatic breast cancer previously treated with two or more HER2-directed regimens, including stable asymptomatic brain disease", "claim": "In the phase 3 NALA trial, 621 patients from 28 countries were assigned to neratinib plus capecitabine (n = 307) or lapatinib plus capecitabine (n = 314). Centrally reviewed progression-free survival was improved with neratinib (HR 0.76; 95% CI 0.63 to 0.93; P = .0059); the overall survival hazard ratio was 0.88 (95% CI 0.72 to 1.07; P = .2098). Interventions for central nervous system disease were fewer with neratinib (cumulative incidence 22.8% v 29.2%; P = .043). Diarrhoea of any grade occurred in 83% versus 66%.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "B-NALA", "nct": "NCT01808573", "acronym": "NALA", "title": "A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 621, "sponsor": "Puma Biotechnology, Inc.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2013-03-29", "lastUpdate": "2021-06-11", "url": "https://clinicaltrials.gov/study/NCT01808573" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Coprimary: centrally confirmed progression-free survival (PFS) and overall survival (OS); trial positive if either was met (α split between end points)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 621, "assessment": "not stated", "quote": "NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial … A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314).", "quote_note": "PFS was 'centrally confirmed'/'centrally reviewed'; blinding of the review is not stated" }, "effect": { "measure": "HR", "value": 0.76, "ci_low": 0.63, "ci_high": 0.93, "ci_level": "95%", "p": ".0059", "endpoint": "Centrally reviewed progression-free survival", "quote": "Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098)." }, "landmark": [ { "endpoint": "Objective response rate", "timepoint": "best overall response (no fixed time point)", "experimental_pct": 32.8, "control_pct": 26.7, "higher_is_better": true, "experimental_arm": "Neratinib plus capecitabine", "control_arm": "Lapatinib plus capecitabine", "quote": "ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201)", "difference_pp": 6.1, "nnt": 17, "quote_note": "P-NALA, J Clin Oncol 2020, only paper provided" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups." }, "takeaway_en": "In patients with HER2-positive metastatic breast cancer previously treated with two or more HER2-directed regimens, including those with stable asymptomatic CNS disease, neratinib plus capecitabine was compared with lapatinib plus capecitabine. Neratinib improved centrally reviewed progression-free survival (HR 0.76). The overall survival difference was not significant (HR 0.88). Objective response was 32.8% versus 26.7% (P = .1201, not significant). All-grade diarrhea was more frequent with neratinib despite loperamide prophylaxis (83% vs 66%), as was nausea (53% vs 42%), while discontinuation rates and quality of life were similar.", "takeaway_ko": "HER2 표적 치료를 2회 이상 받은 HER2 양성 전이성 유방암 환자(안정적이고 무증상인 중추신경계 전이 포함)를 대상으로 네라티닙+카페시타빈과 라파티닙+카페시타빈을 비교했습니다. 네라티닙군에서 중앙 판독 무진행생존기간이 개선되었으나(위험비 0.76), 전체생존기간 차이는 유의하지 않았습니다(위험비 0.88). 객관적 반응률은 32.8% 대 26.7%로 통계적으로 유의하지 않았습니다(P = .1201). 로페라미드 예방 투여에도 불구하고 네라티닙군에서 전체 등급 설사(83% 대 66%)와 오심(53% 대 42%)이 더 흔했으며, 치료 중단율과 건강 관련 삶의 질은 두 군 간에 비슷했습니다.", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-HER2CLIMB02", "trial": "B-HER2CLIMB02", "papers": [ { "key": "P-HER2CLIMB02", "pmid": "41260264", "title": "Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02.", "journal": "Ann Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41260264/", "doi": "10.1016/j.annonc.2025.11.005", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Progression-free survival improved by about two months while the immature overall survival estimate pointed the other way with a wide interval, and severe toxicity was clearly higher. T-DM1 is no longer the usual second-line comparator in many settings. The brain-metastasis subgroup result is not quantified in the abstract.", "label": "HER2CLIMB-02 · tucatinib added to T-DM1", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "After trastuzumab and a taxane, with trastuzumab emtansine", "population": "Previously treated HER2-positive locally advanced or metastatic breast cancer, including brain metastases", "claim": "In the phase III HER2CLIMB-02 study, 463 patients were randomised. After a median follow-up of 24.4 months, median progression-free survival was 9.5 months with tucatinib plus T-DM1 versus 7.4 months with placebo plus T-DM1 (HR 0.76, 95% CI 0.61-0.95, P = 0.0163). The interim overall survival analysis was immature; median overall survival was not reached versus 38.0 months (HR 1.23, 95% CI 0.87-1.74). Grade ≥3 adverse events occurred in 68.8% versus 41.2% and discontinuation of any treatment for adverse events in 22.1% versus 11.6%; grade ≥3 elevated alanine aminotransferase occurred in 16.5% versus 2.6%.", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "B-HER2CLIMB02", "nct": "NCT03975647", "acronym": null, "title": "A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 466, "sponsor": "Seagen, a wholly owned subsidiary of Pfizer", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2019-10-02", "lastUpdate": "2026-07-23", "url": "https://clinicaltrials.gov/study/NCT03975647" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (the abstract reports PFS as the main result of this 'primary analysis' but does not explicitly label it the primary endpoint)", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": 463, "assessment": "not stated", "quote": "Patients were randomly assigned 1 : 1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm. … In total, 463 patients were randomly assigned." }, "effect": { "measure": "HR", "value": 0.76, "ci_low": 0.61, "ci_high": 0.95, "ci_level": "95%", "p": "0.0163", "endpoint": "Progression-free survival", "quote": "After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.61-0.95, P = 0.0163]." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 68.8, "grade3plus_control_pct": 41.2, "discontinuation_experimental_pct": 22.1, "discontinuation_control_pct": 11.6, "treatment_related_deaths": null, "quote": "The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm)." }, "takeaway_en": "In 463 patients with HER2-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane, including patients with brain metastases, adding tucatinib to T-DM1 improved progression-free survival compared with placebo plus T-DM1 (median 9.5 vs 7.4 months; HR 0.76, 95% CI 0.61-0.95). The interim overall survival analysis was immature (HR 1.23, 95% CI 0.87-1.74), and grade ≥3 adverse events were more frequent with tucatinib (68.8% vs 41.2%), mainly liver enzyme elevations, as were adverse events leading to discontinuation of any treatment (22.1% vs 11.6%).", "takeaway_ko": "트라스투주맙과 탁산 치료 후 진행한 HER2 양성 국소 진행성 또는 전이성 유방암 환자 463명(뇌전이 환자 포함)에서, T-DM1에 투카티닙을 추가하자 위약+T-DM1 대비 무진행생존기간이 개선되었습니다(중앙값 9.5개월 대 7.4개월, 위험비 0.76, 95% 신뢰구간 0.61-0.95). 전체생존 중간분석은 아직 미성숙하였고(위험비 1.23, 95% 신뢰구간 0.87-1.74), 3등급 이상 이상반응은 투카티닙군에서 더 많았습니다(68.8% 대 41.2%). 주로 간효소 상승이었으며, 이상반응으로 인한 치료 중단도 더 많았습니다(22.1% 대 11.6%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code; English takeaway aligned with the Korean and the abstract by Claude Opus 5.5, 2026-11-07" } }, { "id": "U-PHILA", "trial": "B-PHILA", "papers": [ { "key": "P-PHILA", "pmid": "37907210", "title": "Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial.", "journal": "BMJ", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37907210/", "doi": "10.1136/bmj-2023-076065", "errata": [ { "pmid": "37973164", "title": "Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial.", "url": "https://pubmed.ncbi.nlm.nih.gov/37973164/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-PHILAOS", "pmid": "41839514", "title": "Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2 positive metastatic breast cancer: long term survival results from randomised phase 3 PHILA trial.", "journal": "BMJ", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41839514/", "doi": "10.1136/bmj-2025-087259", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "The control arm did not include pertuzumab, the usual first-line partner elsewhere, so the trial does not compare pyrotinib with standard dual antibody therapy. The survival P value is described as nominal. Nine in ten patients had severe treatment-related adverse events. All patients were enrolled in China. Both abstracts are one trial; a published correction changed only one author's affiliation.", "label": "PHILA · first-line pyrotinib with trastuzumab and docetaxel", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "First line for metastatic disease", "population": "Untreated HER2-positive metastatic breast cancer, enrolled in China", "claim": "In the double-blind phase 3 PHILA trial, 590 patients received pyrotinib (297) or placebo (293), each with trastuzumab and docetaxel. At the first analysis, median progression-free survival was 24.3 months (95% CI 19.1 to 33.0) versus 10.4 months (9.3 to 12.3) (hazard ratio 0.41, 95% CI 0.32 to 0.53). Grade 3 or higher treatment-related adverse events occurred in 267 of 297 patients (90%) versus 224 of 293 (76%). At the later analysis, with median follow-up of 35.7 and 34.3 months, 59 (20%) versus 87 (30%) patients had died (hazard ratio 0.64, 95% CI 0.46 to 0.89; nominal one-sided P=0.004), and progression-free survival was 22.1 versus 10.5 months (hazard ratio 0.44, 95% CI 0.36 to 0.53).", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "B-PHILA", "nct": "NCT03863223", "acronym": null, "title": "A Study of Pyrotinib in Combination With Trastuzumab and Docetaxel in Patients With HER2 Metastatic Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 590, "sponsor": "Jiangsu HengRui Medicine Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2019-04-22", "lastUpdate": "2022-11-23", "url": "https://clinicaltrials.gov/study/NCT03863223" }, "sources": 3, "corrections": 1, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival as assessed by the investigator", "primary_endpoint_type": "PFS", "design": { "phase": "3", "randomized": true, "blinding": "double-blind", "n_randomized": 590, "assessment": "investigator", "quote": "Randomised, double blind, placebo controlled, multicentre, phase 3 trial. … The primary endpoint was progression-free survival as assessed by the investigator. … Of the 590 randomised patients, 297 received pyrotinib, trastuzumab, and docetaxel treatment (pyrotinib group), and 293 received placebo, trastuzumab, and docetaxel treatment (placebo group)." }, "effect": { "measure": "HR", "value": 0.41, "ci_low": 0.32, "ci_high": 0.53, "ci_level": "95%", "p": "one sided P<0.001", "endpoint": "Investigator-assessed progression-free survival (primary analysis, median follow-up 15.5 months)", "quote": "The median progression-free survival according to the investigator was significantly longer in the pyrotinib group than in the placebo group (24.3 (95% confidence interval 19.1 to 33.0) months versus 10.4 (9.3 to 12.3) months; hazard ratio 0.41 (95% confidence interval 0.32 to 0.53); one sided P<0.001)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": 90, "grade3plus_control_pct": 76, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": "None in the pyrotinib group; one (<1%; diabetic hyperosmolar coma) in the placebo group", "quote": "Treatment related adverse events of grade 3 or higher were reported in 267 (90%) of the 297 patients in the pyrotinib group and 224 (76%) of the 293 patients in the placebo group. No treatment related deaths occurred in the pyrotinib group, and one (<1%; diabetic hyperosmolar coma) treatment related death occurred in the placebo group." }, "takeaway_en": "In 590 women in China with untreated HER2-positive metastatic breast cancer, adding pyrotinib to trastuzumab and docetaxel improved investigator-assessed progression-free survival compared with placebo (hazard ratio 0.41, 95% CI 0.32 to 0.53; median 24.3 vs 10.4 months), and at longer follow-up 20% versus 30% of patients had died (overall survival hazard ratio 0.64, 95% CI 0.46 to 0.89; nominal one-sided P=0.004). Grade 3 or higher treatment-related adverse events were more frequent with pyrotinib (90% vs 76%).", "takeaway_ko": "치료 경험이 없는 중국인 HER2 양성 전이성 유방암 여성 590명에서 트라스투주맙과 도세탁셀에 파이로티닙을 추가하자 위약 대비 연구자 평가 무진행생존기간이 개선되었습니다(위험비 0.41, 95% 신뢰구간 0.32–0.53; 중앙값 24.3개월 대 10.4개월). 장기 추적 시점에 사망한 환자는 20% 대 30%였습니다(전체생존 위험비 0.64, 95% 신뢰구간 0.46–0.89; 명목상 단측 P=0.004). 3등급 이상 치료 관련 이상반응은 파이로티닙군에서 더 많았습니다(90% 대 76%).", "certainty": { "level": "high", "reasons": [ "no concern detected in the abstract" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-T-ESTIMABL2", "trial": "T-ESTIMABL2", "papers": [ { "key": "P-T-ESTIMABL2-22", "pmid": "35263518", "title": "Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.", "journal": "N Engl J Med", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35263518/", "doi": "10.1056/NEJMoa2111953", "errata": [] }, { "key": "P-T-ESTIMABL2-5y", "pmid": "39586309", "title": "Thyroidectomy without radioiodine in patients with low-risk thyroid cancer: 5 years of follow-up of the prospective randomised ESTIMABL2 trial.", "journal": "Lancet Diabetes Endocrinol", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/39586309/", "doi": "10.1016/S2213-8587(24)00276-6", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The end point is a composite of imaging and laboratory abnormalities, most of them biological, not clinical recurrence or death; follow-up is 5 years in a disease with late recurrences. Noninferiority applies to the small, node-negative or node-unassessed tumours enrolled and does not extend to larger tumours, nodal disease or higher-risk features. All patients had total thyroidectomy, so the trial does not address less extensive surgery or observation without surgery. Adults only.", "label": "ESTIMABL2 · thyroidectomy with or without radioiodine in low-risk thyroid cancer", "kind": "rct", "result": "positive", "setting": "After total thyroidectomy; prospective, randomized phase 3 noninferiority trial of no postoperative radioiodine versus ablation with 1.1 GBq after recombinant human thyrotropin", "population": "Low-risk differentiated thyroid cancer (pT1am or pT1b, N0 or Nx); 776 patients enrolled", "claim": "Among 730 patients who could be evaluated 3 years after randomization, the percentage without an event was 95.6% (95% CI 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI -2.7 to 2.2), which met the noninferiority criteria (a difference of less than 5 percentage points). No treatment-related adverse events were reported. In the pre-specified analysis at 5 years, 698 patients were evaluable and the proportions without events were 93.2% and 94.8%, a difference of -1.6% (90% CI -4.5 to 1.4); events were structural or functional abnormalities (n=11) and biological abnormalities (n=31).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "T-ESTIMABL2", "nct": "NCT01837745", "acronym": "ESTIMABL2", "title": "Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 776, "sponsor": "Gustave Roussy, Cancer Campus, Grand Paris", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2013-05-13", "lastUpdate": "2023-05-17", "url": "https://clinicaltrials.gov/study/NCT01837745" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-T-IoN", "trial": "T-ION", "papers": [ { "key": "P-T-IoN25", "pmid": "40543520", "title": "Thyroidectomy with or without postoperative radioiodine for patients with low-risk differentiated thyroid cancer in the UK (IoN): a randomised, multicentre, non-inferiority trial.", "journal": "Lancet", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40543520/", "doi": "10.1016/S0140-6736(25)00629-4", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Few recurrences occurred, so the estimates for the pT3 and N1a subgroups rest on very small numbers and the authors' interpretation limits the conclusion to pT1, pT2 and N0 or Nx tumours without adverse features. Recruitment took nearly eight years. The trial is still in active follow-up. All patients had total thyroidectomy; less extensive surgery and observation without surgery are not addressed. Adults.", "label": "IoN · thyroidectomy with or without radioiodine ablation in the United Kingdom", "kind": "rct", "result": "positive", "setting": "After total thyroidectomy with complete (R0) resection; multicentre, non-inferiority, phase 3 randomised trial at 33 UK cancer centres comparing 1.1 GBq ablation with no ablation", "population": "Low-risk differentiated thyroid cancer: stage pT1, pT2, pT3 or pT3a disease and N0, Nx, or N1a disease; 504 patients recruited between June 26, 2012 and March 18, 2020", "claim": "251 patients were assigned to no ablation and 253 to ablation. Median follow-up was 6.8 years and 6.6 years; 17 recurrences occurred. 5-year recurrence-free rates were 97.9% (95% CI 96.1-99.7) with no ablation versus 96.3% (93.9-98.7) with ablation in the intention-to-treat analysis; the absolute risk difference was 0.5 percentage points (95% CI -2.2 to 3.2), within the margin of 5 percentage points. Recurrence was observed in 9% of 46 patients with pT3 or pT3a tumours vs 3% of 458 with pT1 or pT2 tumours, and in 13% of 47 with N1a vs 2% of 457 with N0 or Nx. Fatigue was reported by 25% of 249 patients without ablation and 28% of 231 with ablation, and there were no treatment-related deaths.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "T-ION", "nct": "NCT01398085", "acronym": "IoN", "title": "IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 504, "sponsor": "University College, London", "sponsorClass": "OTHER", "collaborators": [ "Cancer Research UK" ], "hasResults": false, "start": "2012-06-26", "lastUpdate": "2026-05-07", "url": "https://clinicaltrials.gov/study/NCT01398085" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-HiLo", "trial": "T-HILO", "papers": [ { "key": "P-T-HiLo12", "pmid": "22551128", "title": "Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer.", "journal": "N Engl J Med", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22551128/", "doi": "10.1056/NEJMoa1109589", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The end point is ablation success within a year, not recurrence or survival; this abstract gives no long-term outcome. The noninferiority margin was ten percentage points. The trial compares two doses and does not test giving no radioiodine.", "label": "HiLo · low-dose versus high-dose radioiodine ablation", "kind": "rct", "result": "positive", "setting": "After surgery; randomized noninferiority trial at 29 centers in the United Kingdom comparing 1.1 GBq with 3.7 GBq, each with thyrotropin alfa or thyroid hormone withdrawal", "population": "Differentiated thyroid cancer, tumor stage T1 to T3 with possible spread to nearby lymph nodes but without metastasis; age range 16 to 80 years; 438 patients randomized, 421 analyzed", "claim": "Ablation success rates at 6 to 9 months were 85.0% with low-dose versus 88.9% with high-dose radioiodine, and 87.1% with thyrotropin alfa versus 86.7% with thyroid hormone withdrawal; all 95% confidence intervals for the differences were within ±10 percentage points. More patients in the high-dose group were hospitalized for at least 3 days (36.3% vs. 13.0%, P<0.001). Adverse events occurred in 21% of the low-dose group versus 33% of the high-dose group (P=0.007).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "T-HILO", "nct": "NCT00415233", "acronym": "HiLo", "title": "High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 438, "sponsor": "University College, London", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2006-11", "lastUpdate": "2023-12-19", "url": "https://clinicaltrials.gov/study/NCT00415233" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-ESTIMABL1", "trial": "T-ESTIMABL1", "papers": [ { "key": "P-T-ESTIMABL1-12", "pmid": "22551127", "title": "Strategies of radioiodine ablation in patients with low-risk thyroid cancer.", "journal": "N Engl J Med", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22551127/", "doi": "10.1056/NEJMoa1108586", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The end point is completeness of ablation at 8 months, not recurrence or survival. The abstract does not give the ablation rate for each group. The trial compares doses and preparation methods and does not test giving no radioiodine, which the later trial by the same group addressed.", "label": "ESTIMABL1 · radioiodine dose and stimulation method in low-risk thyroid cancer", "kind": "rct", "result": "positive", "setting": "After total thyroidectomy; randomized phase 3 trial in a 2-by-2 design comparing two thyrotropin-stimulation methods and two radioiodine doses (1.1 GBq and 3.7 GBq), assessed in an equivalence framework", "population": "Low-risk differentiated thyroid carcinoma (pT1 with N1 or Nx, pT1 with any N stage, or pT2N0, without distant metastasis); 752 patients enrolled between 2007 and 2010; 92% had papillary cancer", "claim": "In the 684 patients with data that could be evaluated 8 months after radioiodine, neck ultrasonography was normal in 652 (95%) and thyroid ablation was complete in 631 (92%). The ablation rate was equivalent between the radioiodine doses and between the thyrotropin-stimulation methods. There were no unexpected serious adverse events.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "T-ESTIMABL1", "nct": "NCT00435851", "acronym": "Estimabl", "title": "Medico-Economic Comparison of Four Strategies of Radioiodine Ablation in Thyroid Carcinoma Patients", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 950, "sponsor": "Gustave Roussy, Cancer Campus, Grand Paris", "sponsorClass": "OTHER", "collaborators": [ "National Cancer Institute, France" ], "hasResults": false, "start": "2007-02", "lastUpdate": "2007-02-19", "url": "https://clinicaltrials.gov/study/NCT00435851" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-ASTRA", "trial": "T-ASTRA", "papers": [ { "key": "P-T-ASTRA22", "pmid": "35192411", "title": "Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA).", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35192411/", "doi": "10.1200/JCO.21.00714", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A negative trial of an unselected high-risk population; patients were not selected by tumour genotype, so it does not test the drug in tumours with a specific driver. The end point is complete remission at 18 months, not survival. It does not bear on whether drugs can restore iodine uptake in iodine-refractory disease, which is a different setting.", "label": "ASTRA · selumetinib added to adjuvant radioactive iodine in high-risk differentiated thyroid cancer", "kind": "rct", "result": "negative", "setting": "Adjuvant treatment after surgery; international, phase III, randomized, placebo-controlled, double-blind trial of selumetinib 75 mg twice daily or placebo for approximately 5 weeks around radioactive iodine (3.7 GBq)", "population": "Differentiated thyroid cancer at high risk of primary treatment failure (primary tumor > 4 cm, gross extrathyroidal extension, or nodal disease as defined in the protocol); Four hundred patients enrolled and 233 randomly assigned", "claim": "Patients were assigned 2:1 to selumetinib (n = 155) or placebo (n = 78). There was no statistically significant difference in complete remission rate 18 months after radioactive iodine (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": { "key": "T-ASTRA", "nct": "NCT01843062", "acronym": "ASTRA", "title": "Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer", "status": "TERMINATED", "phases": [ "PHASE3" ], "enrollment": 233, "sponsor": "AstraZeneca", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": true, "start": "2013-08-27", "lastUpdate": "2019-08-28", "url": "https://clinicaltrials.gov/study/NCT01843062" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-PTMCSurveillanceKR18", "trial": null, "papers": [ { "key": "P-PTMCSurveillanceKR18", "pmid": "30226447", "title": "Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma: A Multi-Center Cohort Study in Korea.", "journal": "Thyroid", "year": "2018", "url": "https://pubmed.ncbi.nlm.nih.gov/30226447/", "doi": "10.1089/thy.2018.0263", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Observational with a median follow-up under three years; patients were selected for surveillance and there is no surgical comparison group. Volume increase is a more sensitive measure than diameter increase, so the two percentages are not interchangeable with the diameter-based figures of other cohorts. The absence of a difference by Hashimoto's thyroiditis is a subgroup observation within diagnosed cancers, reported without numbers in the abstract; it says nothing about cancer risk in people with thyroiditis who have no cancer. The denominator for the pathological node finding is not stated in the abstract. Adults with an already diagnosed low-risk cancer.", "label": "Low-risk papillary microcarcinoma under active surveillance · multicentre cohort in Korea", "kind": "observational", "result": "descriptive", "setting": "Multicenter study of patients who underwent active surveillance for more than one year, comparing initial and last ultrasonography; median 32.5 months of follow-up", "population": "370 patients with low-risk papillary thyroid microcarcinoma; age at diagnosis 51 ± 12 years; 110 (30%) were <45 years of age", "claim": "During follow-up, 86 (23.2%) patients had an increase in tumor volume and 13 (3.5%) had an increase in maximal diameter. The cumulative incidence of volume increase rose to 36.2% after five years. The risk of volume increase in patients <45 years of age was twice as high as in older patients (p = 0.002). There was no significant difference in tumor size change according to sex, levothyroxine treatment, or presence of Hashimoto's thyroiditis. Delayed surgery was performed in 58 (15.7%) patients because of anxiety (37.9%), an increase in tumor size (32.8%) or the appearance of cervical lymph node metastasis (8.6%); pathological examination found lymph node metastasis in 29.3%.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PMCObserveJP10", "trial": null, "papers": [ { "key": "P-PMCObserveJP10", "pmid": "20066418", "title": "Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes.", "journal": "World J Surg", "year": "2010", "url": "https://pubmed.ncbi.nlm.nih.gov/20066418/", "doi": "10.1007/s00268-009-0359-x", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Observational, single institution, counted partly by lesion and partly by patient. Patients chose observation and no comparison with immediate surgery is reported. The contrast with symptomatic microcarcinoma is between two differently selected groups treated in different periods. Adults with an already diagnosed, symptom-free microcarcinoma; it says nothing about people without a cancer diagnosis, children or larger tumours.", "label": "Asymptomatic papillary microcarcinoma · single-institution nonsurgical observation since 1995", "kind": "observational", "result": "descriptive", "setting": "Prospective nonsurgical observation of asymptomatic papillary microcarcinoma conducted since 1995 at a single institution; observation for a mean of 5 (range 1-17) years", "population": "230 of 244 candidates (94%) who accepted observation, with 300 lesions", "claim": "Of 300 lesions, 22 (7%) had increased in size, 269 (90%) were unchanged and 9 (3%) had decreased. No patients developed extrathyroidal invasion or distant metastasis. Three patients (1%) who developed apparent lymph node metastasis and nine patients (4%) whose tumor increased in size eventually underwent surgery after 1-12 years of follow-up; no recurrence has been identified after surgery. Among patients operated on for symptomatic microcarcinoma, 10-year cause-specific survival was 80%.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-11", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-INFLUENCEBE26", "trial": null, "papers": [ { "key": "P-INFLUENCEBE26", "pmid": "42858729", "title": "Belgian validation of the INFLUENCE 3.0 model predicting 5-year locoregional and contralateral breast cancer recurrence.", "journal": "Breast", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42858729/", "doi": "10.1016/j.breast.2026.104944", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "These are external authors’ model-validation results, not newly accessed RISCON patient records, own model execution or independent reproduction. Locoregional recurrence and contralateral breast cancer are distinct events; performance for one cannot be transferred to the other, to distant relapse or to cure. Cohort overlap with model development, patient-level preprocessing, follow-up/censoring, competing risks, definitions of recurrence, event counts by year, uncertainty intervals, missingness and model/version fixation require full-method/code review. Small absolute calibration-error metrics in low-risk populations do not erase the reported overestimation. Point-estimate AUC differences between treatment-history groups do not establish a causal effect of neoadjuvant therapy on model performance or statistically proven subgroup differences. The abstract gives no tested surveillance thresholds, prospective treatment/surveillance strategy, decision benefit or outcome improvement. Results from the older single-center clinical population do not establish generalizability across all centers, current treatments or individual patients. No prediction comparison or clinical efficacy claim is added. On 2026-10-20, the newly linked public PMC full text was received and its cohort, outcomes, imputation, validation and data-availability sections were read. It describes a Belgian single-center evaluation, follow-up from definitive surgery, first-event rules, missing-at-random multiple imputation and annually evaluated calibration/discrimination. Eligibility includes an assumption about margin status for unreviewed cases following a sample review; it is not fully adjudicated individual eligibility. Competing-event treatment and calibration estimands require source-code/supplement reconciliation before reuse. The underlying patient dataset is not publicly available; an offered request route is not access and no request was sent. Source code, supplementary methods and independent re-execution remain unreceived. This full-text appraisal does not turn the model into a proven surveillance strategy or add RISCON patient records.", "label": "Belgian INFLUENCE recurrence-risk validation: endpoint and treatment-context differences", "program": "breast", "kind": "analysis", "level": "computational", "result": "mixed", "setting": "External authors’ observational validation of a Dutch risk model at Leuven; surveillance benefit not evaluated", "population": "Female breast cancer patients treated with curative intent at a Belgian center; groups distinguished by receipt of neoadjuvant systemic therapy", "claim": "The authors evaluated the INFLUENCE 3.0 model in 8,548 Leuven patients treated during 2000–2018: 7,549 without neoadjuvant systemic therapy and 999 with it. Annual AUCs for locoregional recurrence were 0.72–0.86 in the former group and above 0.82 in the latter. For contralateral breast cancer, AUC was approximately 0.5 without neoadjuvant systemic therapy and 0.68–0.88 with it. ICI and E50 were below 0.01 in most subgroups, but calibration plots showed risk overestimation, especially at lower predicted risks.", "by": "Codex (GPT-6)", "added": "2026-10-12", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2Lactylation26", "trial": null, "papers": [ { "key": "P-HER2Lactylation26", "pmid": "42860555", "title": "Lactylation-Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer.", "journal": "Adv Sci (Weinh)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42860555/", "doi": "10.1002/advs.77955", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "subtypes": [ "G-HER2" ], "limits": "Positive refers to reported experimental activity, not clinical treatment efficacy. On 2026-10-14, newly available original PMC13655267 was inspected for site-substitution/binding controls, patient classification, animal interventions, statistical methods and data availability. Its mouse survival analysis uses a prespecified tumor-volume humane endpoint; it is not a human survival or cure result. Subcutaneous xenografts in immunodeficient mice, including engineered cells and patient-derived tissue, do not represent all immune contexts or clinical resistance. Body-weight and renal/hepatic observations reported in treated mice do not establish comprehensive normal-tissue safety, human drug interactions or clinically achievable tumor exposure. The patient prognostic association does not establish a treatment-effect modifier or causal survival benefit. Main-text site-mutant controls were read, but supplementary patient tables/images, raw measurements, effect estimates, independent replication, assay specificity, clinical exposure and long-term safety remain unaudited. Stiripentol’s approval for epilepsy does not establish its efficacy, interaction safety or dose for gastric cancer. No human combination trial, breast-cancer transfer, own execution, patient-data access, reproduction or cure claim is added.", "label": "HER2 lactylation and trastuzumab resistance in gastric cancer: an experimental intervention candidate", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "External authors’ mechanistic cellular and in-vivo experiments with a patient prognostic association; clinical combination benefit not tested in this report", "population": "HER2-positive gastric cancer models and resected patient tissues classified by subsequent trastuzumab response, with a separate prognostic tissue-array analysis; patient-level selection remains unaudited", "claim": "The authors report that AARS1-mediated HER2 lactylation at K1171 promotes USP11-mediated deubiquitination, receptor stabilization and HER2–EGFR interaction. Higher HER2 K1171 lactylation was associated with poorer prognosis in gastric cancer patients. Blocking this modification with L-alanine or stiripentol increased trastuzumab sensitivity in tumor cells, and a site-directed cell-penetrating peptide enhanced antitumor effects in vivo.", "by": "Codex (GPT-6)", "added": "2026-10-13", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CDK1Dynamics26", "trial": null, "papers": [ { "key": "P-CDK1Dynamics26", "pmid": "42860544", "title": "Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer.", "journal": "Adv Sci (Weinh)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42860544/", "doi": "10.1002/advs.77920", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "The new public original PMC13655259 was inspected on 2026-10-14 for clinical cohort definitions, cell treatment, statistical methods and data availability. In its NeoPalAna analysis, responder groups are defined using a proliferation marker after palbociclib treatment; this is not a pCR, radiological response or survival endpoint. Activity, expression and distinct phosphorylation sites are different measurements, and exploratory assay cutoffs are not validated clinical treatment-selection thresholds. The metastatic paired-biopsy comparison samples baseline and disease progression during treatment, not a randomized intervention selecting patients by CDK1. Cohort selection, overlap, multiple marker analyses, treatment history and prospective treatment-by-marker interaction remain unresolved. The article states that patient data in its early cohort figures are not public; reported GEO accessions and an article license do not establish access/eligibility for all underlying patient data. No GEO rows, author code, independent model execution or reproduction were received. Main-text method inspection does not audit supplementary material, raw measurements, data split or clinical utility. NeoPalAna remains a correlative input, not an additional efficacy trial. No proof that CDK1 inhibition improves patient outcomes, clinical dosing, drug substitution, subtype transfer or cure inference is made.", "label": "CDK1 dynamics during CDK4/6 inhibition: adaptive-resistance biomarker candidate", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "External authors’ biosensor-mouse/cell experiments integrated with patient cohorts and a NeoPalAna correlative analysis; no new independent clinical efficacy trial counted", "population": "ER-positive breast cancer experimental models and clinical cohorts, including patients observed during CDK4/6 inhibition", "claim": "The authors observed increased CDK1 activity during the transition to invasive ductal carcinoma. Patient analyses linked pCDK1Y15 to poorer relapse-free survival in stage 1 disease. CDK4/6 inhibition initially suppressed the CDK1/cyclin B1 complex, followed by rebound within 3 days. NeoPalAna non-responders incompletely suppressed CDK1, while resistant cells and non-responsive mouse and patient tumors showed recovered or increased CDK1 activity/expression.", "by": "Codex (GPT-6)", "added": "2026-10-13", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CLASP26", "trial": null, "papers": [ { "key": "P-CLASP26", "pmid": "42854913", "title": "Knowledge-guided Multimodal Learning for Interpretable Prediction of Pathological Complete Response and Survival in Breast Cancer.", "journal": "Lab Invest", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42854913/", "doi": "10.1016/j.labinv.2026.106169", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "These are external authors’ reported discrimination results, not RISCON model execution, independent reproduction, newly accessed patient records or a prospective treatment strategy. Patient/slide overlap, foundation-model pretraining exposure, language-prior construction and information cutoff, preprocessing and feature selection within training folds, tuning, frozen model and external-site independence require source-code/full-method audit. The abstract does not report AUC confidence intervals, calibration, clinical thresholds, false-negative rates or decision benefit, and higher point estimates do not establish statistically significant superiority. The reported total spans cohorts; the abstract does not provide each split denominator or few-shot sampling/repetition uncertainty. A few-shot result does not show that a small new clinical dataset suffices for safe deployment. Pathological complete response prediction does not establish the benefit of changing treatment, skipping surgery, long-term survival or cure. The title and model objective include prognosis, but no quantitative prognostic evaluation is supplied in the abstract. Image/text alignment and agreement among language models do not establish a causal resistance mechanism.", "label": "CLASP pathology-informed multimodal pCR prediction in breast cancer", "program": "breast", "kind": "analysis", "level": "computational", "result": "descriptive", "setting": "External authors’ pretreatment pathology/clinical model evaluation, not response-adapted treatment assignment", "population": "Breast cancer cohorts assessed for neoadjuvant-chemotherapy pathological complete response; cohort-level subtype and regimen distribution require full-method review", "claim": "CLASP combines CONCH whole-slide image features, patient clinical data and 16 hierarchical pathology text priors generated by an ensemble of large language models. The authors report evaluation in 1,486 patients from four cohorts, with internal-test AUC 0.881 and external-validation AUCs 0.875 and 0.845. AUC point estimates exceeded those of 11 evaluated baselines. The abstract also reports competitive few-shot performance with 8 training samples and qualitative alignment of highlighted regions with recognized pathological features.", "by": "Codex (GPT-6)", "added": "2026-10-11", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-MetastaticLatency26", "trial": null, "papers": [ { "key": "P-MetastaticLatency26", "pmid": "42867316", "title": "Mutability Dependence of Breast Cancer Metastasis and Latency to Recurrence.", "journal": "Cancer Discov", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42867316/", "doi": "10.1158/2159-8290.CD-25-2090", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The analysis supports an explanatory mutability-dependent model within sampled tumors, not a prospective individual recurrence forecast, causal treatment target or proof that inhibiting mutation accumulation prevents metastasis. Relative timing and pathway selection may depend on phylogenetic/model assumptions, mutation detection sensitivity, biopsy sampling, prior treatment and selection of patients with observed metastases. Full definitions of latency, counts by patient versus tumor/pair, missingness, clone detection, pathway-selection rules, uncertainty, independent fit/evaluation split and cross-cohort overlap remain unreviewed. An explained-variation statement within analyzed data is not out-of-sample prediction accuracy. Findings do not imply that all late recurrence is caused by post-dissemination mutagenesis or establish an APOBEC-directed intervention, dose, safety or clinical benefit. Tumor counts are not newly accessed RISCON patients and are not added to research coverage, own execution, reproduction or prediction comparisons.", "label": "Metastasis-specific mutations and breast recurrence latency: retrospective timing model", "program": "breast", "kind": "genomics", "level": "computational", "result": "descriptive", "setting": "External authors’ analysis of primary/metastatic tumor genomes and an explanatory model of mutation timing; no recurrence-prevention intervention allocated", "population": "Breast primary and metastatic tumor datasets described as paired and unpaired; tumor, pair and patient denominators require full-method review", "claim": "The authors describe genomic data from 662 paired and approximately 6,000 unpaired primary and metastatic tumors. Newly detected metastasis-specific mutations were inferred to be frequently acquired after dissemination, with a disproportionate contribution from APOBEC-mediated mutagenesis. Recurrent pathways varied by metastatic site; 95% of patients had metastasis-specific mutations in a minimum set of 10 pathways. Relative timing of pathway mutation acquisition before versus after dissemination explained more than half the observed variation in metastatic latency.", "by": "Codex (GPT-6)", "added": "2026-10-14", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-Ganetespib26", "trial": "B-Ganetespib26", "papers": [ { "key": "P-Ganetespib26", "pmid": "42873573", "title": "A randomized phase II study of fulvestrant with or without ganetespib in patients with endocrine resistant metastatic breast cancer.", "journal": "Oncologist", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42873573/", "doi": "10.1093/oncolo/oyag414", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-HR" ], "subtypes": [ "B-HRPOS" ], "limits": "Failure to demonstrate improved PFS in this small trial is not an equivalence result or proof against every HSP90 strategy. The abstract does not explicitly attach each median PFS value to an arm in its results sentence; the numbers are retained without assigning an order. The received registry maps the PFS values to treatment arms but labels the primary-outcome parameter as MEAN, while the article abstract calls them medians. The original estimand/type and precision require reconciliation rather than silently treating the two labels as equivalent. Registry rules allow control-arm crossover after progression and ganetespib discontinuation while fulvestrant continues in the combination arm; actual exposure and implications for survival comparisons require full-method review. Adverse-event grades/denominators, censoring and protocol amendments remain unreviewed. Historical treatment context and prior CDK4/6 exposure must be checked before transfer to current treatment sequences. On-treatment biopsy selection and exploratory mutation/subtype associations do not establish a validated treatment-selection assay or causal explanation of failure. The registry already posted results before this publication; this is not a newly conducted trial, prospective RISCON prediction, accessed patient cohort or own experiment. No clinical substitution, preventive benefit or cure inference is made.", "label": "Fulvestrant with ganetespib in endocrine resistance: negative randomized phase II result", "program": "breast", "kind": "rct", "level": "clinical", "result": "negative", "setting": "External randomized phase II comparison of fulvestrant alone versus fulvestrant with HSP90 inhibition in endocrine-resistant metastatic disease; historical completed trial with a newly indexed publication", "population": "Hormone receptor-positive, HER2-negative metastatic breast cancer previously treated with endocrine therapy; a small randomized cohort, not a mutation-selected treatment comparison", "claim": "The abstract reports 50 patients randomized to fulvestrant alone (15) or fulvestrant plus ganetespib (35). Reported median PFS values were 3.7 and 3.6 months, with log-rank p=0.79; no improvement was demonstrated. Diarrhea was reported more frequently with the combination (97% versus 7%), and nausea was also higher. Exploratory profiling of 13 on-treatment biopsies linked lack of clinical benefit to ESR1 alterations and proliferative transcriptional programs.", "by": "Codex (GPT-6)", "added": "2026-10-15", "trialRecord": { "key": "B-Ganetespib26", "nct": "NCT01560416", "acronym": null, "title": "Fulvestrant With or Without Ganetespib in HR+ Breast Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 50, "sponsor": "Dana-Farber Cancer Institute", "sponsorClass": "OTHER", "collaborators": [], "hasResults": true, "start": "2012-06", "lastUpdate": "2026-03-03", "url": "https://clinicaltrials.gov/study/NCT01560416" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Progression-free survival (PFS)", "primary_endpoint_type": "PFS", "design": { "phase": "2", "randomized": true, "blinding": "not stated", "n_randomized": 50, "assessment": "not stated", "quote": "In this randomized phase II study, 50 patients with HR+ MBC previously treated with endocrine therapy were randomized 1:2 to fulvestrant alone (n = 15) or fulvestrant with ganetespib (n = 35), respectively." }, "effect": { "measure": null, "value": null, "ci_low": null, "ci_high": null, "ci_level": null, "p": "0.79 (log-rank)", "endpoint": "Progression-free survival", "quote": "Median PFS was similar between arms (3.7 vs. 3.6 months; log-rank p = 0.79)." }, "landmark": [], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Toxicity was higher with ganetespib, with substantially increased diarrhea (97% vs. 7%) and nausea (63% vs. 40%)." }, "takeaway_en": "In 50 patients with endocrine-resistant HR+, HER2-negative metastatic breast cancer, adding the HSP90 inhibitor ganetespib to fulvestrant did not improve progression-free survival: median PFS was 3.7 vs. 3.6 months (log-rank p = 0.79), and no hazard ratio was reported. The combination caused more toxicity, chiefly diarrhea (97% vs. 7%) and nausea (63% vs. 40%), with no grade 3 or higher rates reported.", "takeaway_ko": "내분비 치료 저항성 HR 양성, HER2 음성 전이성 유방암 환자 50명에서 풀베스트란트에 HSP90 억제제 가네테스핍을 추가해도 무진행 생존기간은 개선되지 않았으며, 중앙 무진행 생존기간은 3.7개월 대 3.6개월이었습니다(log-rank p = 0.79). 위험비는 보고되지 않았습니다. 병용군에서는 독성이 더 많았고, 주로 설사(97% 대 7%)와 오심(63% 대 40%)이 증가했으며, 3등급 이상 이상반응 비율은 보고되지 않았습니다.", "certainty": { "level": "low", "reasons": [ "no confidence interval for the primary effect in the abstract", "fewer than 300 patients randomized" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-ESR1VariantTOT26", "trial": null, "papers": [ { "key": "P-ESR1VariantTOT26", "pmid": "42868272", "title": "Differential impact of tumor-derived ESR1 mutations on elacestrant benefit in metastatic breast cancer.", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42868272/", "doi": "10.1158/1078-0432.CCR-26-2215", "errata": [] } ], "pages": [], "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "subtypes": [ "B-HRPOS" ], "limits": "Insurance-claims treatment discontinuation is not a radiologically assessed progression endpoint, survival benefit or direct drug-effect estimate. Stopping may reflect progression, toxicity, adherence, coverage or other unmeasured factors. Variant associations and molecular expression do not establish that a different drug improves outcomes in a variant subgroup. Treatment line, prior endocrine/CDK4/6 exposure, claims linkage, missingness, discontinuation reasons, co-mutations, clone fractions and the treatment-specific denominators need original-method review. The tumor-sequencing total is not the number of treated patients or independent patient records; repeated tumors and overlap with prior Caris/cBioPortal analyses remain unaudited. There is no randomized treatment-by-variant interaction or prospectively validated cutoff. No EMERALD efficacy estimate is replaced, and no underlying rows, own execution, independent reproduction or cure claim are added.", "label": "ESR1 variant-specific elacestrant duration: claims-based observational association", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "External tumor-sequencing and insurance-claims analysis of elacestrant treatment duration; no randomized comparator or mutation-guided intervention", "population": "ESR1-mutated breast tumors sequenced at Caris Life Sciences, with transcriptome data in a subset; claims-linked treatment analysis denominators require full-method review", "claim": "The authors studied 3,344 ESR1-mutated tumors, with transcriptome sequencing for 1,663. Time-on-treatment was the insurance-claims interval from starting to discontinuing elacestrant. L536 variants were associated with shorter duration than more common Y537 and D538G variants (HR=2.089, p=0.001). Multiple ESR1 mutations were associated with shorter duration than single mutations (adjusted HR=1.62, p=0.038). L536 tumors showed lower GREB1 expression and reduced estrogen-response pathway enrichment.", "by": "Codex (GPT-6)", "added": "2026-10-15", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-CRLMMultistate26", "trial": null, "papers": [ { "key": "P-CRLMMultistate26", "pmid": "42867594", "title": "Recurrence After Resection of Colorectal Liver Metastases and Its Impact on Survival: A Multistate Model-Based, Multi-institutional Observational Cohort Study.", "journal": "Ann Surg Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42867594/", "doi": "10.1245/s10434-026-20765-3", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Original publisher methods, mortality-denominator paragraph, limitations and data availability were inspected on 2026-10-16. The selected surgical registry is observational, with heterogeneous centers, treatment eras and surveillance; state-transition associations do not identify chemotherapy benefit. Follow-up begins at liver surgery, and assumptions about post-surgery treatment timing, selection and possible immortal time require audit before any causal comparison. The model assumes a time-inhomogeneous Markov process and combines first local/distant recurrence; molecular information and tumor-burden data have substantial missingness. Center-specific effects, treatment at recurrence and repeated recurrences were not modeled. Competing-risk/state-occupation probabilities differ from crude observed fractions; being recurrence-free at a landmark conditions on survival and is not a validated individual prediction or cure threshold. On 2026-10-17 the original supplement, transition diagram and baseline/risk-factor tables were inspected. The diagram permits cause-specific death both before and after documented recurrence; published state-occupation and landmark transition probabilities are distinct from first-event recurrence incidence. The supplement provides a reporting checklist and probability tables, not patient rows or executable code. Neither the inspected main methods nor supplement specifies imputation versus complete-case handling, effective transition-specific analysis denominators, or treatment initiation as a time-varying exposure; a checklist page reference does not resolve those omissions. The reported postoperative chemotherapy association remains vulnerable to treatment selection and possible immortal time; a timing bias is a concern to audit, not an established finding about the authors code. Missing-data handling, treatment timing, raw measurements, code and independent calibration remain unresolved. The article explicitly states patient-level study data are not public; article access does not establish dataset access, own computation, reproduction or clinical utility.", "label": "Recurrence after colorectal liver resection: multistate observational prognosis", "program": "colorectal", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "External registry analysis following curative-intent colorectal liver metastasis resection; disease-state transitions and observational chemotherapy associations", "population": "Selected patients undergoing hepatic resection for colorectal liver metastases; palliative procedures, macroscopic residual disease and planned staged hepatectomy excluded in the original methods", "claim": "Among 3,002 patients, 1,624 (54.1%) developed recurrence. The main text of the original article clarifies that the 911 deaths reported (56.1%) were among patients who had a recurrence, not among all patients. The authors modeled being alive without recurrence, alive after recurrence and cause-specific death as distinct states. Tumor burden was associated with transition to recurrence but not with mortality after recurrence, while recorded adjuvant chemotherapy was associated with lower hazards of recurrence and of cancer-related death from the recurrence-free state.", "by": "Codex (GPT-6)", "added": "2026-10-16", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-S100RAGETDXd26", "trial": null, "papers": [ { "key": "P-S100RAGETDXd26", "pmid": "42467226", "title": "Targetable S100-RAGE Signaling Mediates Intrinsic Trastuzumab Deruxtecan Resistance in Metastatic Breast Cancer.", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42467226/", "doi": "10.1158/1078-0432.CCR-25-4894", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [], "limits": "Positive refers to experimental activity, not a tested human combination benefit. Public author manuscript PMC13495545 was inspected for clinical cohort/response definition, spatial-region selection, cell and animal interventions, statistics and data availability. Lesions are clustered within patients and do not represent independent patient records; non-significance of routine markers does not establish their lack of predictive utility. Clinical benefit at first restaging includes stable disease and is not durable control or survival. Morphology-guided region selection and sampling/response classification need independent evaluation. The efficacy models use immunodeficient mice with experimental dissemination; an attempted immunocompetent orthotopic model regressed without treatment, preventing delayed-treatment testing in that setting. This failed model is retained as a limitation, not evidence of spontaneous cure in patients. No longitudinal biopsies support an acquired-resistance trajectory here. Human combination exposure, delivery to metastatic sites, interactions, normal-tissue harm and randomized efficacy remain unverified; availability of an oral antagonist or safety experience elsewhere cannot supply them. On 2026-10-19, official GEO series metadata for the reported accession GSE327983 was received and matched to this paper. It lists spatial RNA/protein assay entries and links to measurement and metadata files; these entries are not verified independent patients or lesions. The series belongs to the original study and cannot serve as an independent external validation cohort for that same finding. Morphology-selected regions, within-patient and within-lesion dependence, RNA/protein and segmentation mapping, response labels and eligibility must be reconciled before any computation. Reuse conditions have not been reviewed for the intended research and any later redistribution; public visibility alone was not treated as complete rights clearance. Supplementary measurements, patient metadata tables and author code were not downloaded or independently executed. Dataset connection, new patient acquisition, reproduction and clinical validation remain unperformed. No breast-subtype transfer, gastric application, own reproduction or cure inference is made. On 2026-10-20, one publicly exported GEO assay record was read for its metadata structure and processing description. It labels a protein library and links a DCC filename and a statistics file; such library identifiers alone do not identify independent patients, lesions or matched compartments. Its processing narrative describes a small spatial tissue subset, quality filters and merging/linking conventions, which must not be substituted for the larger clinical cohort or assumed to apply identically to every listed assay. The record does not by itself establish the response labels or patient/lesion mapping needed for a frozen analysis. Intended-use and reuse conditions remain unverified. No metadata spreadsheet, expression matrix, raw assay archive or author code was downloaded, and no analysis, dataset connection or reproduction was performed.", "label": "S100-RAGE spatial resistance to T-DXd: experimental combination candidate", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "positive", "setting": "External retrospective metastatic-tissue profiling with cell and mouse perturbation experiments; RAGE blockade combined with T-DXd tested experimentally", "population": "An institutional series of T-DXd-treated metastatic breast lesions and selected pretreatment spatial-profiling regions, with HER2-positive cell lines and experimental metastasis models", "claim": "In a cohort of 109 T-DXd-treated metastatic lesions, routine clinicopathologic markers were not significantly associated with response. Resistant tissue regions showed increased S100-family alarmins and RAGE-associated ERK, AKT and STAT3 signaling. Combining T-DXd with the RAGE inhibitor TTP488 increased apoptosis and drug sensitivity in cells and reduced metastatic burden in lung and brain mouse models.", "by": "Codex (GPT-6)", "added": "2026-10-16", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-AkkMSSCRC26", "trial": "C-AkkMSSCRC26", "papers": [ { "key": "P-AkkMSSCRC26", "pmid": "42887494", "title": "Akkermansia muciniphila attenuates macrophage efferocytosis to enhance anti-PD-1 efficacy in microsatellite-stable colorectal cancer.", "journal": "Cell Host Microbe", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42887494/", "doi": "10.1016/j.chom.2026.09.014", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "Abstract plus the official registry were reviewed; publisher full methods and supplements were not received. Clinical activity is descriptive and cannot isolate the contribution of the microbial product or establish reversal of human immunotherapy resistance, a comparative benefit, durable survival or cure. The abstract describes a phase1 trial, while the current registry lists phase not applicable, estimated enrollment and no posted results. Estimated registration size is not the analyzed denominator and is not used to reconstruct a response count. The registry permits anti-PD-1 with tyrosine kinase inhibitors or with chemotherapy and/or bevacizumab, alongside the microbial product, although the abstract summarizes the combination more simply. Actual regimen distribution, prior treatment, response assessment, follow-up, strain/product formulation, concomitant medications and graded harms require original reconciliation. A registry arm labeled self control is still a single-group study, not a randomized concurrent control; generic randomization wording in an outcome does not establish random allocation. The publication calls the combination safe without quantitative adverse-event data in the received abstract; safety, infection risk and applicability to broader hosts remain unverified here. Mouse perturbation mechanisms and response-correlated human immune findings are not interchangeable causal evidence. Do not transfer activity to MSI-high disease, gastric or breast cancer, unrelated probiotic products or routine clinical use. No RISCON patient access, new dataset connection, own computation, reproduction or prospective prediction is counted.", "label": "Akkermansia and PD-1 blockade in MSS colorectal cancer: early combination signal", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "External mechanistic mouse experiments with an early uncontrolled clinical combination report in previously treated metastatic MSS colorectal cancer", "population": "The publication reports metastatic microsatellite-stable colorectal cancer after prior therapy; exact published clinical analysis size and regimen distribution are not supplied in the abstract", "claim": "The authors report that Akkermansia muciniphila suppressed tumorigenesis and modified macrophage clearance of dying cells in mouse models, with activation of innate immune signaling and enhanced anti-PD-1 activity. An early clinical combination study reported an objective response rate of 19% in previously treated metastatic microsatellite-stable colorectal cancer. The abstract does not supply the response numerator or evaluable denominator, a concurrent control or quantitative adverse-event results.", "by": "Codex (GPT-6)", "added": "2026-10-18", "trialRecord": { "key": "C-AkkMSSCRC26", "nct": "NCT06865521", "acronym": null, "title": "Akkermansia Probiotics Plus Anti-PD-1 Monoclonal Antibody in MSS/pMMR Advanced Colorectal Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "NA" ], "enrollment": 22, "sponsor": "West China Hospital", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2025-02-21", "lastUpdate": "2026-04-13", "url": "https://clinicaltrials.gov/study/NCT06865521" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-MechanisticRelapse26", "trial": null, "papers": [ { "key": "P-MechanisticRelapse26", "pmid": "42892345", "title": "A mechanistic learning framework for breast cancer relapse prediction.", "journal": "Math Biosci", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42892345/", "doi": "10.1016/j.mbs.2026.109830", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official PubMed abstract only; full methods, supplements, author code and input measurements have not been received or independently executed. Latent initial cell burden and growth rate are model-derived quantities under an anchored exponential-growth model, not measured disseminated cells, demonstrated dormancy kinetics or individualized biological mechanisms. A reference phenotype can set a parameter scale without validating that biological interpretation. A mathematically positive predicted relapse time is not predictive accuracy. The proposed Seed and Speed components use routine variables; the Soil component is not implemented with directly measured stromal lymphocytes or PD-L1 in METABRIC. Same-cohort proxy/feature-selection experiments are not independent validation. Internal cross-validation and comparable concordance to a Cox baseline do not establish superiority, externally calibrated individual risk, prospective clinical utility or treatment benefit. Censoring, time origin, treatment-era and subtype heterogeneity, nested selection/fitting, model support and transportability require original-source audit. No counterfactual drug effect, prevention of recurrence, gastric/colorectal transfer or cure inference is made. METABRIC availability elsewhere is not evidence of downloading this paper input, verifying access and overlap, locking an independent plan or executing a RISCON reproduction.", "label": "Mechanistic learning of breast relapse: internally evaluated latent growth model", "program": "breast", "kind": "method", "level": "computational", "result": "descriptive", "setting": "External proof-of-concept modeling of historical breast cancer relapse in METABRIC; internal cross-validation versus a Cox baseline", "population": "A historical METABRIC breast cancer cohort with routine histopathological covariates; no newly collected or independently evaluated RISCON patients", "claim": "The authors used METABRIC data from 1,814 patients with 737 relapses to relate routine pathology to latent initial disseminated tumor burden and an effective growth rate. A literature-based reference phenotype anchors the model scale. The proposed microenvironment component was reserved for future datasets because the required directly measured variables were unavailable in this cohort. Internal cross-validation yielded a concordance index of 0.654, comparable to a multivariable Cox baseline. The report presents a proof of concept rather than a clinically validated relapse forecast.", "by": "Codex (GPT-6)", "added": "2026-10-19", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-PaxalisibBrain26", "trial": "B-PaxalisibBrain", "papers": [ { "key": "P-PaxalisibBrain26", "pmid": "42895898", "title": "Paxalisib with Trastuzumab for HER2-Positive Metastatic Breast Cancer with Active Brain Metastases: A Phase II Trial with Integrated Plasma and CSF ctDNA Analyses.", "journal": "Cancer Res Commun", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42895898/", "doi": "10.1158/2767-9764.CRC-26-0571", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "Official abstract and the matching original ClinicalTrials.gov protocol/results were reviewed; journal full methods, supplements and patient-level measurements were not received. This is failure of the tested regimen and primary response endpoint in a small, heavily pretreated population, not proof that the whole pathway is ineffective in every setting. The response denominator is the recommended-dose cohort, not everyone in the safety run-in. Registry efficacy outcomes use that cohort and corroborate the absent confirmed CNS responses. The planned surgical/translational cohort enrolled no participants, so the planned matched resected-tissue/PDX correlation was not demonstrated by registration alone. Registry results were first posted before this publication; this is not a newly disclosed trial or a prospective RISCON prediction. Overall survival is uncontrolled and cannot estimate a survival benefit. Exploratory CSF fraction association does not validate a treatment-switch threshold, independent predictor, clinical utility or improved survival. Feasibility does not mean absence of graded harms; exposure, dose limitations and event denominators require full review. Neither blood-brain penetration nor preclinical regression guarantees human response. No new RISCON patients, own execution, reproduction or cure is counted.", "by": "Codex (GPT-6)", "added": "2026-10-20", "label": "Paxalisib plus trastuzumab: no confirmed CNS responses at the recommended dose", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "negative", "setting": "Nonrandomized phase II combination study in active or progressive HER2-positive breast cancer brain metastases after multiple prior therapies", "population": "Previously treated HER2-positive breast cancer with active brain metastases; leptomeningeal disease excluded", "claim": "Seventeen patients were treated, with a median of 5 prior therapy lines. At the recommended phase II dose, none of 12 patients had a confirmed CNS response: ORR was 0% (95% CI 0.0–26.5%), and the study closed for futility. Median overall survival was 16.5 months. Exploratory measurements showed higher tumor fraction in CSF than plasma, with longitudinal CSF changes paralleling CNS tumor burden.", "trialRecord": { "key": "B-PaxalisibBrain", "nct": "NCT03765983", "acronym": null, "title": "GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases", "status": "TERMINATED", "phases": [ "PHASE2" ], "enrollment": 17, "sponsor": "Dana-Farber Cancer Institute", "sponsorClass": "OTHER", "collaborators": [ "Kazia Therapeutics Limited" ], "hasResults": true, "start": "2019-02-25", "lastUpdate": "2026-05-27", "url": "https://clinicaltrials.gov/study/NCT03765983" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-HypoMastIMNI26", "trial": "B-HypoMastIMNI", "papers": [ { "key": "P-HypoMastIMNI26", "pmid": "42896129", "title": "Hypofractionated Versus Conventionally Fractionated Postmastectomy Radiotherapy With Internal Mammary Node Irradiation for High-Risk Breast Cancer (HypoMast-IMNI): A Randomized Phase III Trial.", "journal": "J Clin Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42896129/", "doi": "10.1200/JCO-25-02843", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official abstract and original registry identity/design were received; full publication, locked statistical analysis plan and supplements were not reviewed. Positive describes the reported locoregional noninferiority result and lower acute skin toxicity, not superior survival or cure. Noninferiority is specific to its margin, endpoint, population, fractionation and radiation fields; it does not mean exact equality or justify omission of nodal irradiation. The margin, its prospective fixation, exclusions from the randomized population, per-protocol agreement, event adjudication, competing risks, multiplicity and uncertainty require full-method audit. A modified intention-to-treat analysis is not automatically the complete randomized cohort. The registry lists phase not applicable while the article describes a phase III radiation study; do not silently equate these labels. No results module is posted in the received registry. Registration occurred after the recorded study start, so original protocol timing needs review. No significant survival difference does not establish survival equivalence. Absence of recorded ischemic events during this follow-up cannot exclude rare or later cardiac harm; pulmonary and other late toxicity surveillance, reconstruction, technique and subgroup applicability remain relevant. No RISCON treatment experiment, own patient acquisition or prospective prediction is added.", "by": "Codex (GPT-6)", "added": "2026-10-20", "label": "HypoMast-IMNI: locoregional noninferiority and reduced acute skin toxicity", "program": "breast", "kind": "rct", "level": "clinical", "result": "positive", "setting": "Postmastectomy chest-wall and regional-node radiotherapy including internal mammary nodes for high-risk operable breast cancer", "population": "Patients with high-risk operable breast cancer after mastectomy, assigned to hypofractionated or conventionally fractionated treatment with internal mammary irradiation", "claim": "The trial randomized 1,494 patients; the modified intention-to-treat population comprised 1,429, with median follow-up of 58.1 months. Five-year locoregional recurrence was 1.7% versus 2.2% (HR 0.69, 95% CI 0.32–1.51), meeting the reported noninferiority criterion. Grade 3 acute skin toxicity was 1.7% versus 12.2%. No significant differences in distant metastasis-free, breast cancer recurrence-free, disease-free or overall survival were reported.", "trialRecord": { "key": "B-HypoMastIMNI", "nct": "NCT03856372", "acronym": null, "title": "Hypofractionated Vs Conventional Fractionated Postmastectomy Radiotherapy for High Risk Breast Cancer", "status": "COMPLETED", "phases": [ "NA" ], "enrollment": 1494, "sponsor": "Fudan University", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2018-09-01", "lastUpdate": "2026-09-03", "url": "https://clinicaltrials.gov/study/NCT03856372" }, "sources": 2, "corrections": 0, "analysisRecord": null, "clinical": { "primary_endpoint": "Locoregional recurrence (LRR)", "primary_endpoint_type": "other", "design": { "phase": "3", "randomized": true, "blinding": "not stated", "n_randomized": null, "assessment": "not stated", "quote": "In this phase III noninferiority trial, eligible patients with high-risk disease after mastectomy … were randomly assigned (1:1) to HypoRT (42.56 Gy in 16 fractions) or conventionally fractionated radiotherapy (ConvRT; 50 Gy in 25 fractions) … Between September 2018 and July 2022, 1,494 patients were randomly assigned." }, "effect": { "measure": "HR", "value": 0.69, "ci_low": 0.32, "ci_high": 1.51, "ci_level": "95%", "p": ".017 (for noninferiority)", "endpoint": "Locoregional recurrence", "quote": "the 5-year cumulative incidence of LRR was 1.7% (95% CI, 0.9 to 2.9) with HypoRT and 2.2% (95% CI, 1.3 to 3.5) with ConvRT (hazard ratio, 0.69 [95% CI, 0.32 to 1.51]), meeting the noninferiority criterion (P = .017)." }, "landmark": [ { "endpoint": "Cumulative incidence of locoregional recurrence", "timepoint": "5 years", "experimental_pct": 1.7, "control_pct": 2.2, "higher_is_better": false, "experimental_arm": "Hypofractionated RT (42.56 Gy in 16 fractions)", "control_arm": "Conventionally fractionated RT (50 Gy in 25 fractions)", "quote": "After a median follow-up of 58.1 months in the modified intention-to-treat population (n = 1,429), the 5-year cumulative incidence of LRR was 1.7% (95% CI, 0.9 to 2.9) with HypoRT and 2.2% (95% CI, 1.3 to 3.5) with ConvRT.", "difference_pp": -0.5, "nnt": 200, "quote_note": "Single paper: J Clin Oncol 2026" } ], "harms": { "grade3plus_experimental_pct": null, "grade3plus_control_pct": null, "discontinuation_experimental_pct": null, "discontinuation_control_pct": null, "treatment_related_deaths": null, "quote": "Grade 3 acute skin toxicity was significantly lower with HypoRT (1.7% v 12.2%, P < .001). The incidence of grade ≥2 radiation pneumonitis and pulmonary fibrosis was low and comparable between arms, with no ischemic cardiac events recorded.", "quote_note": "Overall grade ≥3 adverse events, discontinuation and treatment-related deaths were not reported." }, "takeaway_en": "In patients with high-risk operable breast cancer receiving postmastectomy radiotherapy that included the internal mammary nodes, 16-fraction hypofractionated radiotherapy was compared with 25-fraction conventional radiotherapy. Five-year locoregional recurrence was 1.7% versus 2.2% (HR 0.69, 95% CI 0.32–1.51), which met noninferiority, and grade 3 acute skin toxicity was lower with hypofractionation (1.7% vs 12.2%), with low and comparable rates of radiation pneumonitis and pulmonary fibrosis.", "takeaway_ko": "내유림프절 조사를 포함한 유방전절제술 후 방사선치료가 필요한 고위험 수술 가능 유방암 환자에서 16회 소분할 방사선치료와 25회 통상분할 방사선치료를 비교했습니다. 5년 국소구역 재발률은 1.7% 대 2.2%(위험비 0.69, 95% 신뢰구간 0.32–1.51)로 비열등성 기준을 충족했습니다. 3등급 급성 피부 독성은 소분할군에서 더 낮았고(1.7% 대 12.2%), 방사선 폐렴과 폐섬유화는 두 군 모두 낮고 비슷했습니다.", "certainty": { "level": "moderate", "reasons": [ "confidence interval includes no effect" ] }, "by": "Claude Opus 5.5 from the stored abstracts, 2026-11-07; numbers checked against the abstracts by code; absolute differences, numbers needed to treat and certainty computed by code" } }, { "id": "U-nacGSOXLong26", "trial": null, "papers": [ { "key": "P-nacGSOXLong26", "pmid": "42894432", "title": "Minimum 7-Year Follow-Up of a Prospective Phase II Trial of Preoperative S-1 Plus Oxaliplatin Chemotherapy for Clinical Stage III Gastric Cancer.", "journal": "Asia Pac J Clin Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42894432/", "doi": "10.1111/ajco.70214", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official abstract, the Japanese ministry portal and the directly linked original UMIN registry were received. This is one nonrandomized uncontrolled trial and its later follow-up, not several independent trials or evidence that SOX is better than another regimen. Survival reflects preoperative treatment, surgery, postoperative therapy, selection and subsequent care together; there is no isolated causal contribution for the short preoperative course. Long follow-up of survivors is distinct from long-term survival of everyone and cannot establish cure. No loss to follow-up does not replace a systematic late-toxicity assessment. Postoperative nodal status is measured after treatment and its association is not a validated pretreatment treatment-selection rule. Primary response, registered progression-free survival and reported relapse-free survival need endpoint reconciliation. The received original registry still displays recruiting and an older update; it does not corroborate current recruitment. Public registration follows the listed planned study start, so prospective registration and analysis fixation cannot be assumed. Japanese and English eligibility text differ in the upper age and renal-function conditions and need reconciliation before exact eligibility transfer. Full methods, the earlier report, protocol, participant flow and harms were not audited. No new NCT identifier, independent patient acquisition, own reproduction, regimen recommendation or cure inference is made.", "by": "Codex (GPT-6)", "added": "2026-10-20", "label": "Preoperative SOX in stage III gastric cancer: long-term follow-up of a single uncontrolled cohort", "registry": { "system": "UMIN-CTR", "id": "UMIN000036139", "url": "https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000036850&type=summary&language=J" }, "program": "gastric", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "Two preoperative SOX cycles, D2 gastrectomy and postoperative adjuvant therapy in clinical stage III gastric cancer", "population": "A small Japanese prospective single-arm clinical stage III gastric cancer cohort receiving perioperative multimodality treatment", "claim": "Thirty-four patients were analyzed. The preoperative treatment completion rate was 100%, the R0 resection rate 97.1% and the postoperative adjuvant therapy completion rate 61.8%. All surviving patients had at least 7 years of follow-up; 18 patients had died and 16 remained alive. Five-year overall survival and relapse-free survival were 61.8% and 58.8%, respectively. Associations with nodal status and the preoperative inflammatory ratio were exploratory. Severe treatment-related late adverse events were not documented, but late toxicities were not systematically assessed.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ALASCCA", "trial": "C-ALASCCA", "papers": [ { "key": "P-ALASCCA25", "pmid": "40961426", "title": "Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40961426/", "doi": "10.1056/NEJMoa2504650", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary end point was recurrence in group A only; the group B result and all disease-free survival results are secondary, and disease-free survival in group A did not reach significance. The abstract reports no overall survival result. Fewer than a third of screened patients were eligible, and the trial does not test aspirin in tumours without PI3K pathway alterations. Severe adverse events were more frequent with aspirin. A single trial; PIK3CA, PIK3R1 and PTEN are not atlas targets in this programme, so no target is linked.", "label": "ALASCCA · low-dose aspirin after surgery for PI3K-altered colorectal cancer", "kind": "rct", "result": "positive", "setting": "After treatment of localized disease; double-blind, randomized, placebo-controlled trial of 160 mg of aspirin or placebo once daily for 3 years", "population": "Stage I, II, or III rectal cancer or stage II or III colon cancer with somatic PI3K pathway alterations; alterations were detected in 1103 of 2980 patients (37.0%) with complete genomic data", "claim": "Of 515 patients with PIK3CA exon 9 or 20 hotspot mutations (group A) and 588 with other PIK3CA, PIK3R1 or PTEN alterations (group B), 314 and 312, respectively, were randomized. In group A, the estimated 3-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo (hazard ratio 0.49; 95% CI 0.24 to 0.98; P = 0.04); in group B it was 7.7% and 16.8% (hazard ratio 0.42; 95% CI 0.21 to 0.83). Estimated 3-year disease-free survival in group A was 88.5% and 81.4% (hazard ratio 0.61; 95% CI 0.34 to 1.08), and in group B 89.1% and 78.7% (hazard ratio 0.51; 95% CI 0.29 to 0.88). Severe adverse events occurred in 16.8% of aspirin recipients and 11.6% of placebo recipients.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "C-ALASCCA", "nct": "NCT02647099", "acronym": "ALASCCA", "title": "Adjuvant Low Dose Aspirin in Colorectal Cancer", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE3" ], "enrollment": 626, "sponsor": "Anna Martling", "sponsorClass": "OTHER", "collaborators": [ "Uppsala University Hospital", "Skane University Hospital" ], "hasResults": true, "start": "2016-04-07", "lastUpdate": "2026-03-13", "url": "https://clinicaltrials.gov/study/NCT02647099" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CHALLENGE", "trial": "C-CHALLENGE", "papers": [ { "key": "P-CHALLENGE25", "pmid": "40450658", "title": "Structured Exercise after Adjuvant Chemotherapy for Colon Cancer.", "journal": "N Engl J Med", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40450658/", "doi": "10.1056/NEJMoa2502760", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Participants and staff could not be blinded to an exercise programme, and recruitment spanned fifteen years. The authors describe the overall survival result as supporting rather than confirming a benefit. The comparison is a structured, supported programme against written materials, so it does not show what amount or type of exercise is needed outside such a programme. Colon cancer after adjuvant chemotherapy only; it does not extend to rectal or metastatic disease or to other cancers.", "label": "CHALLENGE · structured exercise programme after adjuvant chemotherapy for colon cancer", "kind": "rct", "result": "positive", "setting": "After resection and completed adjuvant chemotherapy; phase 3 randomized trial at 55 centers of a 3-year structured exercise programme versus health-education materials alone", "population": "889 patients with resected colon cancer randomized from 2009 through 2024 (445 exercise, 444 health education)", "claim": "At a median follow-up of 7.9 years, disease-free survival was longer in the exercise group (hazard ratio for disease recurrence, new primary cancer, or death 0.72; 95% CI 0.55 to 0.94; P = 0.02); 5-year disease-free survival was 80.3% versus 73.9% (difference 6.4 percentage points; 95% CI 0.6 to 12.2). For overall survival the hazard ratio for death was 0.63 (95% CI 0.43 to 0.94), with 8-year overall survival 90.3% versus 83.2%. Musculoskeletal adverse events occurred in 18.5% versus 11.5% of patients.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "C-CHALLENGE", "nct": "NCT00819208", "acronym": "CHALLENGE", "title": "Health Education Materials With/Out a Physical Activity Program for Patients Who Have Undergone Treatment for High-Risk Stage II or Stage III Colon Cancer", "status": "COMPLETED", "phases": [ "NA" ], "enrollment": 889, "sponsor": "Canadian Cancer Trials Group", "sponsorClass": "NETWORK", "collaborators": [ "Survivorship Research Group", "Queen's University, Belfast" ], "hasResults": true, "start": "2009-06-02", "lastUpdate": "2026-04-24", "url": "https://clinicaltrials.gov/study/NCT00819208" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-LEAP017", "trial": "C-LEAP017", "papers": [ { "key": "P-LEAP017-24", "pmid": "38833658", "title": "Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.", "journal": "J Clin Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/38833658/", "doi": "10.1200/JCO.23.02736", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A negative primary result; the point estimate favoured the combination but did not cross the prespecified boundary, and it should not be read as proof of no effect in any subgroup. Open-label. The combination caused more severe adverse events. Applies to previously treated pMMR or not MSI-H disease; it does not bear on MSI-H or dMMR cancer.", "label": "LEAP-017 · lenvatinib plus pembrolizumab in previously treated pMMR colorectal cancer", "kind": "rct", "result": "negative", "setting": "After progression on standard treatment; international, randomized, open-label phase III study of lenvatinib 20 mg daily plus pembrolizumab 400 mg every 6 weeks versus investigator's choice of regorafenib or trifluridine/tipiracil", "population": "Unresectable mismatch repair proficient or not MSI-H metastatic colorectal cancer; 480 patients randomized between April 8, 2021, and December 21, 2021 (241 and 239)", "claim": "At final analysis (median follow-up 18.6 months), median overall survival was 9.8 versus 9.3 months (hazard ratio 0.83; 95% CI 0.68 to 1.02; P = .0379 against a prespecified threshold of P = .0214), so the primary end point was not met. Grade ≥3 treatment-related adverse events occurred in 58.4% versus 42.1% of patients, and two participants died of treatment-related adverse events, both in the combination arm.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "C-LEAP017", "nct": "NCT04776148", "acronym": null, "title": "Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 563, "sponsor": "Merck Sharp & Dohme LLC", "sponsorClass": "INDUSTRY", "collaborators": [ "Eisai Inc." ], "hasResults": true, "start": "2021-03-29", "lastUpdate": "2026-02-05", "url": "https://clinicaltrials.gov/study/NCT04776148" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-DCRC02", "trial": "C-DCRC02", "papers": [ { "key": "P-DCRC02-24", "pmid": "39116902", "title": "Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial.", "journal": "Lancet Oncol", "year": "2024", "url": "https://pubmed.ncbi.nlm.nih.gov/39116902/", "doi": "10.1016/S1470-2045(24)00380-2", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "Randomization was only between two doses and there is no comparison with another treatment, so response rates are not comparative effects; the 5.4 mg/kg group combines randomized and later non-randomized patients. Follow-up was under one year. Interstitial lung disease, including a fatal event, is a known risk of this drug. The abstract does not separate results by RAS status or HER2 level.", "label": "DESTINY-CRC02 · two doses of trastuzumab deruxtecan in HER2-positive colorectal cancer", "kind": "single-arm", "result": "positive", "setting": "Pretreated metastatic disease; multicentre, two-stage phase 2 study randomizing 5.4 mg/kg versus 6.4 mg/kg in stage 1, then enrolling only 5.4 mg/kg in stage 2", "population": "Pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer; 122 patients enrolled between March 5, 2021, and March 29, 2022", "claim": "The confirmed objective response rate by blinded independent central review was 37.8% (31/82; 95% CI 27.3-49.2) with 5.4 mg/kg and 27.5% (11/40; 14.6-43.9) with 6.4 mg/kg. Grade 3 or worse drug-related adverse events occurred in 34 (41%) of 83 and 19 (49%) of 39 patients. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in seven (8%) patients at 5.4 mg/kg, all grade 1 or 2, and in five (13%) at 6.4 mg/kg, including one grade 5 event; one death related to treatment occurred at 5.4 mg/kg (hepatic failure).", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "C-DCRC02", "nct": "NCT04744831", "acronym": "DESTINY-CRC02", "title": "Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 122, "sponsor": "Daiichi Sankyo", "sponsorClass": "INDUSTRY", "collaborators": [ "AstraZeneca" ], "hasResults": true, "start": "2021-03-05", "lastUpdate": "2026-01-14", "url": "https://clinicaltrials.gov/study/NCT04744831" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-AtezoTRIBE", "trial": "C-ATEZOTRIBE", "papers": [ { "key": "P-AtezoTRIBE22", "pmid": "35636444", "title": "Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial.", "journal": "Lancet Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35636444/", "doi": "10.1016/S1470-2045(22)00274-1", "errata": [] } ], "pages": [], "targets": [ "CD274" ], "biomarkers": [], "subtypes": [], "limits": "A phase 2 trial judged with 80% confidence intervals and a relaxed significance level; it is meant to justify a confirmatory trial, not to establish benefit. Open-label, Italian centres only, with a short follow-up and no overall survival result in this abstract. The abstract does not report results for proficient and deficient mismatch repair tumours separately, so the share of the effect in microsatellite-stable disease is not shown here.", "label": "AtezoTRIBE · atezolizumab added to first-line FOLFOXIRI and bevacizumab", "kind": "rct", "result": "positive", "setting": "First-line treatment of unresectable metastatic disease; multicentre, open-label, randomised phase 2 study at 22 centres in Italy, assigned 1:2 to FOLFOXIRI plus bevacizumab with or without atezolizumab", "population": "218 patients with previously untreated metastatic colorectal cancer (73 control, 145 atezolizumab), not selected by mismatch repair status in the abstract", "claim": "At a median follow-up of 19.9 months, median progression-free survival was 13.1 months (80% CI 12.5-13.8) with atezolizumab and 11.5 months (10.0-12.6) without (hazard ratio 0.69 [80% CI 0.56-0.85]; p=0.012). Serious adverse events were reported in 39 (27%) and 19 (26%) patients, and two (1%) treatment-related deaths occurred in the atezolizumab group.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "C-ATEZOTRIBE", "nct": "NCT03721653", "acronym": "AtezoTRIBE", "title": "FOLFOXIRI + Bev + Atezo vs FOLFOXIRI + Bev as First-line Treatment of Unresectable Metastatic Colorectal Cancer Patients", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 218, "sponsor": "Gruppo Oncologico del Nord-Ovest", "sponsorClass": "OTHER", "collaborators": [ "Roche Pharma AG" ], "hasResults": false, "start": "2018-11-30", "lastUpdate": "2023-10-12", "url": "https://clinicaltrials.gov/study/NCT03721653" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-LENVA211", "trial": "T-LENVA211", "papers": [ { "key": "P-T-LENVA211-22", "pmid": "34664662", "title": "A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.", "journal": "J Clin Endocrinol Metab", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/34664662/", "doi": "10.1210/clinem/dgab731", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The end point is response at 24 weeks, not progression-free or overall survival. The abstract does not give the number of patients per arm. The lower starting dose did not reduce severe adverse events by a clear margin. The result concerns the starting dose; it does not test later dose reductions, which were common in the earlier phase 3 trial.", "label": "Study 211 · lenvatinib starting dose 18 mg versus 24 mg in radioiodine-refractory thyroid cancer", "kind": "rct", "result": "negative", "setting": "Randomized, double-blinded comparison of two starting doses of lenvatinib; noninferiority judged on objective response rate at week 24 with an odds-ratio margin of 0.4", "population": "Radioiodine-refractory differentiated thyroid cancer", "claim": "Objective response rate as of week 24 was 57.3% (95% CI 46.1, 68.5) with 24 mg and 40.3% (95% CI 29.3, 51.2) with 18 mg, odds ratio 0.50 (95% CI 0.26, 0.96), so noninferiority of the lower starting dose was not shown. Grade ≥3 treatment-emergent adverse events as of week 24 occurred in 61.3% and 57.1%, a difference of -4.2% (95% CI -19.8, 11.4).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "T-LENVA211", "nct": "NCT02702388", "acronym": null, "title": "A Trial of Lenvatinib (E7080) in Subjects With Iodine-131 Refractory Differentiated Thyroid Cancer to Evaluate Whether an Oral Starting Dose of 18 Milligram (mg) Daily Will Provide Comparable Efficacy to a 24 mg Starting Dose, But Have a Better Safety Profile", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 241, "sponsor": "Eisai Inc.", "sponsorClass": "INDUSTRY", "collaborators": [ "Merck Sharp & Dohme LLC" ], "hasResults": true, "start": "2017-06-08", "lastUpdate": "2021-11-24", "url": "https://clinicaltrials.gov/study/NCT02702388" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-T-Donafenib23", "trial": null, "papers": [ { "key": "P-T-Donafenib23", "pmid": "37184934", "title": "Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.", "journal": "Clin Cancer Res", "year": "2023", "url": "https://pubmed.ncbi.nlm.nih.gov/37184934/", "doi": "10.1158/1078-0432.CCR-22-3613", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Placebo-controlled in Chinese patients only; it does not compare donafenib with lenvatinib or sorafenib. Crossover to open-label donafenib after progression means overall survival, not reported in the abstract, would be hard to interpret. The abstract does not state a trial registration, so no registry is linked here.", "label": "Donafenib in progressive radioiodine-refractory differentiated thyroid cancer · Chinese phase III trial", "kind": "rct", "result": "positive", "setting": "Multicenter, double-blind, placebo-controlled phase III study, randomized 2:1 to donafenib 300 mg twice daily or placebo, with open-label donafenib allowed after progression", "population": "191 Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (128 donafenib, 63 placebo)", "claim": "Median progression-free survival by independent review was 12.9 versus 6.4 months (hazard ratio 0.39; 95% CI 0.25-0.61; P < 0.0001). Objective response rate was 23.3% versus 1.7% and disease control rate 93.3% versus 79.3%. With donafenib, grade ≥ 3 treatment-related adverse events included hypertension (13.3%) and hand-foot syndrome (12.5%); 42.2% underwent dose reduction or interruption and 6.3% discontinued.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-T-ALTER01031", "trial": "T-ALTER01031", "papers": [ { "key": "P-T-ALTER01031-21", "pmid": "33832949", "title": "Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial.", "journal": "Clin Cancer Res", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33832949/", "doi": "10.1158/1078-0432.CCR-20-2950", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A phase IIB trial with fewer than one hundred patients, conducted in China; the interval for the hazard ratio is wide. The placebo group's median progression-free survival was long, which reflects slow disease in many patients and makes cross-trial comparison with other medullary cancer trials unreliable. The abstract does not report results by RET mutation status or an overall survival result.", "label": "ALTER 01031 · anlotinib in advanced medullary thyroid carcinoma", "kind": "rct", "result": "positive", "setting": "Multicenter, randomized, double-blind, placebo-controlled phase IIB study, randomized 2:1 to anlotinib 12 mg on days 1 to 14 every 3 weeks or placebo, with open-label anlotinib after progression", "population": "Unresectable locally advanced or metastatic medullary thyroid cancer; Ninety-one patients enrolled", "claim": "Median progression-free survival was 20.7 months with anlotinib versus 11.1 months with placebo (P = 0.029; hazard ratio 0.53; 95% CI 0.30-0.95). The objective response rate with anlotinib was 48.4%. Treatment-related adverse events occurred in 100% and 89.7% of patients; the most common with anlotinib were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%) and hypertriglyceridemia (48.4%).", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-20", "trialRecord": { "key": "T-ALTER01031", "nct": "NCT02586350", "acronym": null, "title": "Study of Anlotinib in Patients With Medullary Thyroid Carcinoma(ALTER01031)", "status": "COMPLETED", "phases": [ "PHASE2", "PHASE3" ], "enrollment": 91, "sponsor": "Chia Tai Tianqing Pharmaceutical Group Co., Ltd.", "sponsorClass": "INDUSTRY", "collaborators": [], "hasResults": false, "start": "2015-07", "lastUpdate": "2019-05-21", "url": "https://clinicaltrials.gov/study/NCT02586350" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-A8", "trial": null, "papers": [ { "key": "P-MSIUpdate15", "pmid": "25701956", "title": "Microsatellite instability: an update.", "journal": "Arch Toxicol", "year": "2015", "url": "https://pubmed.ncbi.nlm.nih.gov/25701956/", "doi": "10.1007/s00204-015-1474-0", "errata": [] }, { "key": "P-GiannakisCRC16", "pmid": "27149842", "title": "Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma.", "journal": "Cell Rep", "year": "2016", "url": "https://pubmed.ncbi.nlm.nih.gov/27149842/", "doi": "10.1016/j.celrep.2016.03.075", "errata": [ { "pmid": "27760322", "title": "Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma.", "url": "https://pubmed.ncbi.nlm.nih.gov/27760322/", "reviewed": true, "unresolvedIdentifier": false } ] }, { "key": "P-SeshagiriCRC12", "pmid": "22895193", "title": "Recurrent R-spondin fusions in colon cancer.", "journal": "Nature", "year": "2012", "url": "https://pubmed.ncbi.nlm.nih.gov/22895193/", "doi": "10.1038/nature11282", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "The association is well established; agreement with it confirms the handling of the public data rather than adding new biology. MSI labels come from each study and indeterminate labels were excluded. Sporadic and inherited MSI-high tumours are not separated, and there is no adjustment for age, tumour side or stage. Many MSK patients also appear in earlier MSK analyses in this library. A molecular co-occurrence pattern is not a treatment effect.", "label": "A8 · BRAF V600E by MSI status in three colorectal cancer cohorts", "program": "colorectal", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A8", "setting": "Prespecified reanalysis of three public colorectal cancer cohorts, one primary and two replications tested separately; the plan was locked and published before the BRAF mutation records were requested", "population": "Colorectal cancer patients with a determined MSI label, one sample per patient", "claim": "BRAF V600E was more frequent in MSI-high than in microsatellite-stable tumours in the primary MSK cohort and in the DFCI replication cohort, and the prespecified exact test and interval supported that direction in both. The small Genentech cohort pointed the same way but was inconclusive. Counts, intervals and tests are in the linked analysis record.", "by": "Claude", "added": "2026-10-20", "trialRecord": null, "sources": 4, "corrections": 1, "analysisRecord": { "id": "A8", "title": "BRAF V600E by MSI status in three colorectal cancer cohorts", "retrieved": "2026-10-20", "method": "One sample per patient with a determined MSI label, primary tumour preferred where sample type is recorded; BRAF V600E is a missense call with protein change V600E in the public mutation profile; MSI-high and microsatellite-stable groups compared with a two-sided Fisher exact test and a Newcombe-Wilson 95% interval for the difference, in each cohort separately. The MSK 2026 cohort is primary; DFCI 2016 and Genentech 2012 are prespecified replications, not pooled." } }, { "id": "U-TDXdILA26", "trial": null, "papers": [ { "key": "P-TDXdILA26", "pmid": "42897999", "title": "Equivocal and definite interstitial lung abnormalities as risk factors for trastuzumab deruxtecan-related interstitial lung disease in breast cancer.", "journal": "Oncologist", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42897999/", "doi": "10.1093/oncolo/oyag420", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [], "subtypes": [], "limits": "Official abstract only; full methods, reader blinding/agreement, prior CTs, covariate model, severity/attribution adjudication and competing-event definitions were not reviewed. This retrospective single-center association does not establish that the baseline finding causes ILD, an externally validated individual risk rule or benefit from a particular screening, surveillance, exclusion or treatment-change strategy. Selection into T-DXd treatment and prior treatment/host factors may affect the association. The reported subdistribution hazard ratio is not an individual absolute probability or a cause-specific rate. Failure to detect a difference between equivocal and definite findings is not equivalence, especially with small groups. First detection during earlier systemic treatment does not establish that treatment caused the finding. No significant survival difference does not establish absence of survival impact or equal treatment benefit. Do not transfer this population incidence to every breast subtype, another ADC, gastric cancer or an individual patient. No newly accessed RISCON patients, own computation, risk-model validation or cure claim is added.", "by": "Codex (GPT-6)", "added": "2026-10-21", "label": "Baseline lung abnormalities and T-DXd-associated ILD: retrospective risk association", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Baseline CT findings before T-DXd initiation in advanced or recurrent breast cancer at a Japanese tertiary hospital", "population": "Consecutive T-DXd recipients with baseline CT categorized as no, equivocal or definite interstitial lung abnormalities", "claim": "Among 156 patients, 50 had baseline interstitial lung abnormalities. T-DXd-related interstitial lung disease occurred in 19 of 50 patients with abnormalities and 12 of 106 without them. Baseline abnormalities were associated with higher cumulative ILD incidence in a competing-risk analysis (subdistribution HR 3.56, 95% CI 1.63–7.78). No significant difference was detected between equivocal and definite abnormalities, or in progression-free or overall survival according to baseline abnormality status. The findings describe an association in treated patients.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-EosinophilHR26", "trial": null, "papers": [ { "key": "P-EosinophilHR26", "pmid": "42900864", "title": "Association of Circulating Eosinophils With Systemic Immune Activation and Reduced Recurrence in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.", "journal": "J Clin Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42900864/", "doi": "10.1200/JCO-26-00261", "errata": [] } ], "pages": [], "targets": [ "CDK4/6" ], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "Official abstract only; full methods, subgroup provenance, treatment assignment, prespecified cutpoint and interaction estimates were not received. Cohort sizes and the authors’ description of independence do not establish independent RISCON validation, patient-level overlap resolution or access to their data. Subgroup counts must not be summed as additional distinct patients. Prognosis and prediction of differential treatment benefit are separate questions: a treated-group association or adjusted/weighted comparison is not automatically a randomized treatment-by-biomarker interaction. Baseline timing, treatment initiation, follow-up, confounding, positivity and missing-data handling, infection/allergy/steroid influences, feature selection, calibration and external threshold transport require audit. The abstract does not establish that the clinical treatment comparison was randomized; this uncertainty is retained rather than assuming either proof or a design error. Preclinical eosinophil transfer and immune associations do not show that raising a human blood count prevents relapse or improves CDK4/6 efficacy. No individual treatment selection, extra cancer programme, own experiment, new dataset connection, new patient acquisition or cure conclusion is made.", "by": "Codex (GPT-6)", "added": "2026-10-21", "label": "Eosinophils, recurrence and CDK4/6 benefit: biomarker association requiring interaction audit", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "External authors’ cohort and translational study of preoperative eosinophils in hormone receptor-positive/HER2-negative breast cancer", "population": "A discovery cohort, an expanded cohort and molecular-score and adjuvant CDK4/6-treatment subgroups whose overlap is unresolved here; these are not newly accessed RISCON patient data", "claim": "The authors studied a discovery cohort of 472 patients and an expanded cohort of 23,170, with analyses involving 2,973 patients with gene recurrence scores and 3,471 high-risk patients for the CDK4/6-inhibitor question. Higher preoperative eosinophils were associated with better recurrence-related outcomes, with multivariable and propensity-score-weighted analyses. The abstract also reports additive prognostic information and a claim of greater treatment benefit in a selected subgroup, alongside mouse and immune-profiling experiments. Effect sizes, decision thresholds and a randomized treatment-by-biomarker interaction are not supplied in the abstract.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-ACTOrganoid26", "trial": null, "papers": [ { "key": "P-ACTOrganoid26", "pmid": "42882816", "title": "Functional Deconstruction of AC-T Chemotherapy Reveals Interindividual Heterogeneity and Independent Drug Action in Breast Cancer.", "journal": "Cancers (Basel)", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42882816/", "doi": "10.3390/cancers18193121", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official abstract was re-received and the publicly available PMC13664322 methods, statistical, score-definition and availability passages archived on 2026-10-20 were re-read. The Probability of Chemotherapeutic Efficacy name does not establish a calibrated probability: its formula combines growth-response metrics with free plasma exposure and chosen weighting. RECIST-inspired score bins are explicitly not clinical RECIST response. Complete-case organoids are selected from successful cultures and do not represent every original biopsy or patient. Cell-line and organoid viability assays, exposure duration, metabolite handling, schedules and actual tumor exposure require reconciliation with clinical chemotherapy. A best-constituent correlation does not by itself establish independent drug action or exclude synergy; an AC combination experiment is not the entire sequential clinical AC-T regimen. Public cell-line computational transfer is not independent clinical validation or proof of chemotherapy de-escalation safety. The paper states that human raw data are not public and processed data are available on request; no request was sent and no input/code was acquired or executed. Prospective patient outcome correlation, frozen thresholds and independent validation remain necessary. No own simulation, prediction comparison, patient acquisition, treatment recommendation or cure is counted.", "by": "Codex (GPT-6)", "added": "2026-10-21", "label": "AC-T component heterogeneity and a constructed organoid response score", "program": "breast", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "External in silico, breast cell-line and patient-derived organoid experiments on individual AC-T components and AC combination activity", "population": "Breast-derived models and a complete-case organoid subset; public cell-line application is separate from independent patient-outcome validation", "claim": "Among 21 organoids with complete drug-response datasets, the authors reported heterogeneous responses to chemotherapy components. Their constructed exposure and growth-response score classified 62% of organoids as partial-response-like or complete-response-like under AC, compared with 48%, 38% and 14% under the individual components. AC activity was associated with the most active constituent within each model. These are in vitro score categories and hypothesis-generating observations, not measured patient radiological response rates or calibrated probabilities of clinical benefit.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-QBS72S26", "trial": "B-QBS72S", "papers": [ { "key": "P-QBSLMD26", "pmid": "42565554", "title": "Phase 2 test of QBS72S for breast cancer leptomeningeal disease.", "journal": "Neuro Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42565554/", "doi": "10.1093/neuonc/noag177", "errata": [] }, { "key": "P-QBSProtocol25", "pmid": "40813655", "title": "Adaptive cohort design and LAT1 expression scale: study protocol for a Phase 2a trial of QBS72S in breast cancer brain metastases.", "journal": "BMC Cancer", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/40813655/", "doi": "10.1186/s12885-025-14282-x", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official publication/protocol abstracts and the original registry protocol/results were received. One trial is represented by one unit; the leptomeningeal paper is not a separate trial or a newly released result merely because registry results were posted later. In the newly posted registry, the parenchymal cohort-stage response denominator is six, with no complete or partial responses; its next stage did not enroll. This must not be substituted for the breast leptomeningeal denominator or pooled with it as one response population. The registry lists progression-free and overall-survival entries as participant-number outcomes, not median months; response-duration and adverse-event denominators/units require original reconciliation. Related adverse events are reported as events across distinct cohorts and cannot be read as counts or percentages of unique patients. The third, other-primary leptomeningeal cohort is not evidence for all cancers in this programme. Detection in CSF, transporter staining and preclinical activity do not establish therapeutic exposure at every CNS lesion, selective clinical benefit or safety. Stability or improvement in selected participants is not automatically confirmed radiological response or cure; response criteria, assessability, confirmation, follow-up, severity, attribution, treatment history and cohort-specific analysis need full-method review. No ranking against another failed brain-metastasis regimen, isolated causal effect, prospective RISCON prediction, new own patient access, execution or reproduction is added. LAT1 lacks an approved atlas target and is not relabeled as another catalog entry.", "label": "QBS72S: separate leptomeningeal observations and parenchymal response cohort", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "descriptive", "setting": "Early nonrandomized study with distinct parenchymal brain-metastasis and leptomeningeal-disease cohorts; later registry posting must be mapped by cohort", "population": "Breast cancer CNS metastasis populations defined separately by disease compartment; other-primary leptomeningeal participants in the registry are outside this breast evidence interpretation", "claim": "The reported breast cancer leptomeningeal analysis included 10 participants. The authors detected QBS72S in cerebrospinal fluid and described long-term radiographic stability or improvement lasting 6–7 months in two participants. These are early uncontrolled observations, not a confirmed objective response rate, comparative survival benefit or validated biomarker-guided treatment result. The linked protocol assigns the primary response endpoint to the separate parenchymal-metastasis cohort.", "by": "Codex (GPT-6)", "added": "2026-10-21", "trialRecord": { "key": "B-QBS72S", "nct": "NCT05305365", "acronym": null, "title": "Study Assessing QBS72S For Treating Brain Metastases", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 21, "sponsor": "Melanie Hayden Gephart", "sponsorClass": "OTHER", "collaborators": [ "Quadriga Biosciences, Inc." ], "hasResults": true, "start": "2022-08-16", "lastUpdate": "2026-10-20", "url": "https://clinicaltrials.gov/study/NCT05305365" }, "sources": 3, "corrections": 0, "analysisRecord": null }, { "id": "U-A9", "trial": null, "papers": [ { "key": "P-ThyFollicularGenetics25", "pmid": "41175860", "title": "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells.", "journal": "Eur Thyroid J", "year": "2025", "url": "https://pubmed.ncbi.nlm.nih.gov/41175860/", "doi": "10.1530/ETJ-25-0104", "errata": [] }, { "key": "P-MSK50K26", "pmid": "41895280", "title": "Cancer type-specific variation in patterns of driver alterations across 50,000 tumors.", "journal": "Cancer Cell", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41895280/", "doi": "10.1016/j.ccell.2026.03.003", "errata": [ { "pmid": "42001850", "title": "Cancer type-specific variation in patterns of driver alterations across 50,000 tumors.", "url": "https://pubmed.ncbi.nlm.nih.gov/42001850/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The association is well established; agreement with it confirms the handling of the public data rather than adding new biology. Histology is the type recorded in the portal, not a centrally reviewed diagnosis, and the comparison group combines four types with very different BRAF frequencies. The cohort is a tertiary-referral series enriched for advanced disease. The source is distributed under CC BY-NC-ND 4.0, so only aggregate results are shown. A molecular co-occurrence pattern is not a treatment effect.", "label": "A9 · BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer, MSK-IMPACT 50K", "program": "thyroid", "kind": "analysis", "level": "computational", "result": "descriptive", "analysis": "A9", "setting": "Prespecified reanalysis of a public single-institution clinical sequencing cohort; the plan was locked and published before the BRAF mutation records were requested", "population": "Thyroid cancer patients with papillary, follicular, Hurthle cell, poorly differentiated or anaplastic carcinoma, one sample per patient with the primary tumour preferred", "claim": "BRAF V600E was more frequent in papillary carcinoma than in the other follicular-cell-derived types taken together, and the prespecified exact test and interval supported that direction. Counts, the interval and the test are in the linked analysis record.", "by": "Claude", "added": "2026-10-21", "trialRecord": null, "sources": 3, "corrections": 1, "analysisRecord": { "id": "A9", "title": "BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer, MSK-IMPACT 50K", "retrieved": "2026-10-21", "method": "Thyroid cancer samples of the MSK-IMPACT 50K portal study; one sample per patient, primary tumour preferred; papillary carcinoma compared with follicular, Hurthle cell, poorly differentiated and anaplastic carcinoma taken together (medullary carcinoma not compared); BRAF V600E is a missense call with protein change V600E in the public mutation profile; two-sided Fisher exact test and Newcombe-Wilson 95% interval for the difference. Only aggregate results are published (CC BY-NC-ND 4.0 source)." } }, { "id": "U-PD1MaintenanceCRC26", "trial": null, "papers": [ { "key": "P-PD1MaintenanceCRC26", "pmid": "42901720", "title": "Observation versus maintenance immunotherapy after PD-1-induced clinical complete response in dMMR/MSI-H colorectal cancer managed non-operatively: a multicenter cohort study.", "journal": "J Immunother Cancer", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42901720/", "doi": "10.1136/jitc-2026-016538", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "subtypes": [ "C-MSI" ], "limits": "The official PubMed abstract was absent when this unit was created on 2026-10-22 and was received on 2026-10-23. The official publisher original abstract, methods, results and limitations were already received and read. The qualitative public claim retains no numerical effect or participant estimate; this newly received abstract does not change the selected-cohort interpretation. Post-response treatment was decided by patients and physicians rather than randomized, and measured-confounder overlap weighting cannot remove residual confounding. Selection requires response, non-operative choice, evaluable assessments and sufficient follow-up, excluding nonresponders and surgical patients; it is not an intention-to-treat estimate from treatment initiation. Follow-up starts at confirmed clinical response, whereas group membership depends on subsequent treatment exposure. The authors examined a landmark sensitivity analysis and a stricter exposure definition; these do not prove complete elimination of treatment-timing bias. Few oncological events limit precision and nonsignificance is not equivalence or noninferiority. Colon response used operational criteria distinct from established multimodal rectal criteria; a selected surgical pathology subset does not validate every non-operative clinical response. Disease-free survival includes all-cause death and is not proof of tumor eradication or cure. Safety ascertainment was unblinded, surveillance and regimens varied, and follow-up differed by group. Detailed supplemental tables, original code, patient-level data and prospective validation were not received or executed. No independent RISCON validation, new patient acquisition, treatment recommendation or forecast is counted.", "by": "Codex (GPT-6)", "added": "2026-10-22", "label": "Observation or maintenance after clinical complete response: selected non-operative colorectal cohort", "program": "colorectal", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Observation versus continued checkpoint blockade after clinical complete response and entry into non-operative management in an external multicenter cohort", "population": "Selected dMMR/MSI-H colorectal cancer patients achieving clinical complete response; rectal, colon and synchronous primary groups and baseline metastatic status are distinct", "claim": "In patients selected for clinical complete response and non-operative management, the authors observed favorable disease-free survival with both observation and maintenance immunotherapy, and did not detect a clear additional survival benefit from maintenance. Locoregional regrowth was uncommon and was managed with salvage treatment. Additional toxicity after complete response was more frequent with continued treatment. These observational findings motivate prospective evaluation of treatment duration; they do not establish equivalence or the safety of omitting treatment or surgery.", "updated": "2026-10-23", "updatedBy": "Codex (GPT-6)", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-FABP4Peritoneal26", "trial": null, "papers": [ { "key": "P-FABP4Peritoneal26", "pmid": "42892353", "title": "FABP4 drives gastric cancer peritoneal metastasis by inhibiting ferroptosis via UBR4/ALOX15-mediated arachidonic acid metabolism.", "journal": "Cell Signal", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/42892353/", "doi": "10.1016/j.cellsig.2026.112958", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Official PubMed abstract only; full methods, model identities, sample provenance, perturbation specificity, rescue experiments, replication, animal allocation/blinding, pharmacologic exposures and safety were not reviewed. Expression in human metastatic tissue and a mechanism in experimental models do not establish that inhibiting the pathway treats an established human metastasis or prevents clinical recurrence. Genetic and pharmacologic interventions, primary growth and dissemination, and prevention versus treatment settings require separation. Effects on lipid transfer, peroxidation, ferroptosis and metastatic burden need their own measured endpoints and controls; none becomes a calibrated clinical response or cure probability. FABP4, CD36, UBR4 and ALOX15 are not existing target-atlas entities and were not relabeled as an approved catalog target. No own simulation, new connected dataset, patient acquisition, clinical efficacy or independent replication is counted.", "by": "Codex (GPT-6)", "added": "2026-10-22", "label": "Adipocyte-linked ferroptosis resistance in gastric peritoneal metastasis", "program": "gastric", "kind": "preclinical", "level": "preclinical", "result": "descriptive", "setting": "External mechanistic study of adipocyte-derived lipid handling and ferroptosis resistance in gastric peritoneal metastasis", "population": "Gastric cancer experimental models and peritoneal metastatic tissue observations described in the abstract", "claim": "The authors report that adipocytes increased FABP4 expression through PPAR-gamma-dependent signaling and that FABP4 cooperated with CD36 in acquiring adipocyte-derived arachidonic acid while limiting its peroxidation. Their experiments link stabilization of UBR4 with degradation of ALOX15 and suppression of ferroptosis, providing a mechanistic hypothesis for gastric peritoneal metastasis. The reported axis identifies a candidate research target rather than an established human treatment.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2ResidualDiscord26", "trial": null, "papers": [ { "key": "P-HER2ResidualDiscord26", "pmid": "40968607", "title": "Alteration of HER2 Status Following Neoadjuvant Chemotherapy in Breast Cancer: A Clinicopathological Analysis Focusing on HER2-Low Status.", "journal": "Cancer Res Treat", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/40968607/", "doi": "10.4143/crt.2025.761", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B", "BM-HER2LOW-B" ], "subtypes": [], "limits": "Official PubMed abstract and public PMC13680079 methods/discussion were read. The residual-disease paired subset excludes pathological complete responders and cannot estimate conversion in all treated patients. Regimens included chemotherapy with and without HER2-targeted therapy; treatment and subtype composition can confound group differences. The study grouped HER2 0, low and positive using IHC and confirmatory ISH; it did not separately test an ultralow treatment-selection category. Initially discordant cases were reviewed by an experienced pathologist, whereas initially concordant cases were not all re-reviewed. This selective review is not blinded reproducibility assessment of the entire cohort. Biopsy/resection sampling, heterogeneity, pre-analytic factors and reader variation can contribute to discordance; a change in category does not by itself prove therapy-induced clonal evolution or causal resistance. Prognostic models used data-driven covariate selection and DFS started at neoadjuvant treatment initiation although discordance required later residual surgical tissue; this is not a prospectively validated baseline rule. No significant response difference within hormone-receptor groups is not proof of equivalence. The authors’ proposal to retest does not establish benefit or safety of assigning an ADC in this residual early-disease setting, and metastatic HER2-low trial effects cannot simply be transferred. Supplemental data, independent patient-level inputs, code and an externally validated treatment decision policy were not received or executed. No new own patients, simulation, independent clinical validation or cure is counted.", "by": "Codex (GPT-6)", "added": "2026-10-23", "label": "HER2 discordance after neoadjuvant therapy: residual-disease selection and measurement", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Retrospective comparison of pretreatment core biopsies and residual resection specimens after neoadjuvant systemic therapy", "population": "A single-institution breast cancer cohort; paired status analysis restricted to patients with residual disease after neoadjuvant therapy", "claim": "The authors reviewed 1,063 treated patients and used paired specimens from 670 with residual disease. HER2 discordance was reported in 21.2%, most often zero-to-low conversion (11.5%), followed by low-to-positive conversion (3.6%). Lower pathological response in the overall HER2-low group was not statistically different within hormone-receptor subgroups. Discordance was associated with poorer disease-free survival, particularly in the hormone-receptor-positive subgroup. These findings describe classification changes and prognosis, not benefit from a reassessment-guided treatment strategy.", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-INTEGRAL26", "trial": "B-INTEGRAL", "papers": [ { "key": "P-INTEGRAL26", "pmid": "41661218", "title": "A Phase II Study of Docetaxel and Pembrolizumab plus Interleukin 12 Gene Therapy in Nonmetastatic, Anthracycline-Refractory Triple-Negative Breast Cancer (INTEGRAL).", "journal": "Clin Cancer Res", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/41661218/", "doi": "10.1158/1078-0432.CCR-25-2649", "errata": [ { "pmid": "42817702", "title": "Correction: A Phase II Study of Docetaxel and Pembrolizumab plus Interleukin 12 Gene Therapy in Nonmetastatic, Anthracycline-Refractory Triple-Negative Breast Cancer (INTEGRAL).", "url": "https://pubmed.ncbi.nlm.nih.gov/42817702/", "reviewed": true, "unresolvedIdentifier": false } ] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [ "B-TNBC" ], "limits": "The official abstract, public PMC13012616 clinical methods/results and original registry NCT04095689 were read. This small uncontrolled, stopped cohort cannot estimate comparative efficacy or isolate IL-12 toxicity from the complete regimen, infections, progression and host factors. Prior checkpoint therapy varied; the initial participants also received L-NMMA before its removal, and vector dosing changed nonrandomly, so dose groups are not a safety or efficacy comparison. Death attribution in the report includes investigator judgment and uncertainty, not proof of a single molecular cause. The PMC body labels one response among eight as 25%, inconsistent with the abstract’s 12.5%; that body percentage is not used and remains unresolved. The registry outcome title says pathological complete response but its description gives radiological RECIST criteria; endpoint concordance is not certified. The linked publisher correction adds an omitted author and updates contributions/disclosures; its complete short notice paragraph was returned from the official publisher in web search, while direct DOI HTML returned403. No alternate blocked route was requested. That authorship notice does not resolve the response-percentage or registry-definition discrepancy. Favorable mouse effects and cytokine changes, especially in a single responder, do not establish a human predictor or clinical benefit. Participant-level data require institutional approval/request and were not accessed; no contact, own simulation, reproduction, patient acquisition or cure is counted. Registry eligibility defines ER/PR negativity as less than 10% IHC staining; individual expression values were not received, so transport to differently defined receptor-negative or low-positive cohorts is unresolved.", "by": "Codex (GPT-6)", "added": "2026-10-24", "label": "INTEGRAL: early termination of intratumoral IL-12 combination in anthracycline-refractory TNBC", "program": "breast", "kind": "single-arm", "level": "clinical", "result": "negative", "setting": "Single-center open-label neoadjuvant docetaxel/pembrolizumab with intratumoral adenoviral IL-12 after anthracycline-refractory disease", "population": "Selected nonmetastatic triple-negative breast cancer with residual disease after anthracycline therapy; prior immunotherapy exposure and protocol treatment changed during enrollment", "claim": "The abstract reports 8 enrolled patients, with grade 3 or higher adverse events in 87.5% and two treatment-related deaths, leading to early termination for toxicity. Only one patient (12.5%) achieved pathological complete response. Vector dosing was reduced during the trial. The observed combination safety failure and limited response are recorded; this is not a randomized estimate of an individual component’s benefit or proof that every IL-12 delivery strategy is ineffective.", "trialRecord": { "key": "B-INTEGRAL", "nct": "NCT04095689", "acronym": "INTEGRAL", "title": "Docetaxel Chemotherapy and Pembrolizumab Plus Interleukin-12 Gene Therapy in Triple Negative Breast Cancer", "status": "TERMINATED", "phases": [ "PHASE2" ], "enrollment": 8, "sponsor": "The Methodist Hospital Research Institute", "sponsorClass": "OTHER", "collaborators": [ "Merck Sharp & Dohme LLC" ], "hasResults": true, "start": "2021-05-12", "lastUpdate": "2026-01-23", "url": "https://clinicaltrials.gov/study/NCT04095689" }, "sources": 2, "corrections": 1, "analysisRecord": null }, { "id": "U-FIRE3", "trial": "C-FIRE3", "papers": [ { "key": "P-FIRE3-14", "pmid": "25088940", "title": "FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial.", "journal": "Lancet Oncol", "year": "2014", "url": "https://pubmed.ncbi.nlm.nih.gov/25088940/", "doi": "10.1016/S1470-2045(14)70330-4", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The primary endpoint, objective response, was not met; the overall survival difference is a secondary result without a progression-free survival difference, so its cause is not shown. Open-label. Selection used KRAS exon 2 only, not the extended RAS testing used today, and the abstract gives no result by tumour side. EGFR is not an atlas target, so no target is linked.", "label": "FIRE-3 · FOLFIRI with cetuximab or bevacizumab as first-line treatment", "kind": "rct", "result": "mixed", "setting": "First-line treatment of metastatic disease; randomised, open-label phase 3 trial in Germany and Austria comparing FOLFIRI plus cetuximab with FOLFIRI plus bevacizumab", "population": "KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer; 592 patients randomly assigned between Jan 23, 2007, and Sept 19, 2012", "claim": "Objective response, the primary endpoint, was 62.0% (184 of 297) with cetuximab and 58.0% (171 of 295) with bevacizumab (odds ratio 1.18, 95% CI 0.85-1.64; p=0.18). Median progression-free survival was 10.0 versus 10.3 months (hazard ratio 1.06, 95% CI 0.88-1.26). Median overall survival was 28.7 versus 25.0 months (hazard ratio 0.77, 95% CI 0.62-0.96; p=0.017). Grade 3 or worse skin reactions occurred in 26% versus 2% of patients.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-30", "trialRecord": { "key": "C-FIRE3", "nct": "NCT00433927", "acronym": null, "title": "5-FU, Folinic Acid and Irinotecan (FOLFIRI) Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment Colorectal Cancer (CRC)", "status": "UNKNOWN", "phases": [ "PHASE3" ], "enrollment": 568, "sponsor": "PD Dr. med. Volker Heinemann", "sponsorClass": "OTHER", "collaborators": [ "Merck KGaA, Darmstadt, Germany" ], "hasResults": false, "start": "2007-01", "lastUpdate": "2014-03-14", "url": "https://clinicaltrials.gov/study/NCT00433927" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CALGB80405", "trial": "C-CALGB80405", "papers": [ { "key": "P-CALGB80405-17", "pmid": "28632865", "title": "Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.", "journal": "JAMA", "year": "2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28632865/", "doi": "10.1001/jama.2017.7105", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A negative primary result; it does not show the two antibodies are equivalent. Chemotherapy backbone was chosen, not randomized. Selection used KRAS testing available at the time, not extended RAS and BRAF testing, and the abstract gives no result by tumour side. EGFR is not an atlas target, so no target is linked.", "label": "CALGB/SWOG 80405 · cetuximab or bevacizumab with first-line chemotherapy", "kind": "rct", "result": "negative", "setting": "First-line treatment of advanced or metastatic disease in the United States and Canada; cetuximab or bevacizumab randomised, added to mFOLFOX6 or FOLFIRI chosen by physician and patient", "population": "1137 patients with KRAS wild-type colorectal cancer randomized between November 2005 and March 2012 (578 cetuximab, 559 bevacizumab)", "claim": "Median overall survival, the primary end point, was 30.0 months with cetuximab-chemotherapy and 29.0 months with bevacizumab-chemotherapy (stratified hazard ratio 0.88, 95% CI 0.77-1.01; P = .08). Median progression-free survival was 10.5 versus 10.6 months (hazard ratio 0.95), and response rates were 59.6% versus 55.2% (P = .13).", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-30", "trialRecord": { "key": "C-CALGB80405", "nct": "NCT00265850", "acronym": null, "title": "Cetuximab and/or Bevacizumab Combined With Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 2334, "sponsor": "Alliance for Clinical Trials in Oncology", "sponsorClass": "OTHER", "collaborators": [ "National Cancer Institute (NCI)", "SWOG Cancer Research Network", "Bristol-Myers Squibb", "Aptuit" ], "hasResults": true, "start": "2005-11", "lastUpdate": "2026-08-07", "url": "https://clinicaltrials.gov/study/NCT00265850" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-TRIPLETE", "trial": "C-TRIPLETE", "papers": [ { "key": "P-TRIPLETE22", "pmid": "35666229", "title": "Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO.", "journal": "J Clin Oncol", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35666229/", "doi": "10.1200/JCO.22.00839", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A negative trial for the intensified chemotherapy backbone; open-label and Italian sites only. The abstract reports no overall survival result and gives no toxicity numbers. It does not test intensification with bevacizumab or in RAS-mutant disease.", "label": "TRIPLETE · mFOLFOXIRI versus modified FOLFOX with panitumumab", "kind": "rct", "result": "negative", "setting": "First-line treatment of unresectable metastatic disease; prospective, open-label phase III trial at 57 Italian sites, randomized 1:1", "population": "Previously untreated RAS and BRAF wild-type metastatic colorectal cancer; 435 patients enrolled from September 2017 to September 2021 (217 control, 218 experimental)", "claim": "RECIST response, the primary end point, was 73% with mFOLFOXIRI plus panitumumab and 76% with modified FOLFOX plus panitumumab (odds ratio 0.87, 95% CI 0.56 to 1.34, P = .526). Early tumor shrinkage, depth of response and R0 resection rate (25% versus 29%) did not differ, nor did median progression-free survival (12.7 versus 12.3 months; hazard ratio 0.88, 95% CI 0.70 to 1.11). The authors report increased gastrointestinal toxicity with the intensified backbone.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-30", "trialRecord": { "key": "C-TRIPLETE", "nct": "NCT03231722", "acronym": "TRIPLETE", "title": "First Line mFOLFOXIRI + PANITUMUMAB vs mFOLFOX + PANITUMUMAB IN RAS AND BRAF WT METASTATIC COLORECTAL CANCER PATIENTS", "status": "COMPLETED", "phases": [ "PHASE3" ], "enrollment": 435, "sponsor": "Gruppo Oncologico del Nord-Ovest", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2017-09-13", "lastUpdate": "2023-01-05", "url": "https://clinicaltrials.gov/study/NCT03231722" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-JCOG0603", "trial": null, "papers": [ { "key": "P-JCOG0603-21", "pmid": "34520230", "title": "Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial.", "journal": "J Clin Oncol", "year": "2021", "url": "https://pubmed.ncbi.nlm.nih.gov/34520230/", "doi": "10.1200/JCO.21.01032", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "Disease-free survival improved while 5-year overall survival was numerically lower with chemotherapy; the authors state it remains unclear whether chemotherapy improves overall survival. Early termination for disease-free survival can exaggerate that effect. Japanese centres only. The abstract does not give a trial registration, so none is linked.", "label": "JCOG0603 · hepatectomy with or without adjuvant mFOLFOX6 for liver-only metastases", "kind": "rct", "result": "mixed", "setting": "After resection of liver metastases; phase II or III randomized trial of hepatectomy alone versus 12 courses of adjuvant mFOLFOX6", "population": "Patients aged 20-75 years with colorectal cancer and an unlimited number of liver-only metastatic lesions; 300 patients randomly assigned between March 2007 and January 2019", "claim": "The trial was terminated early at the third interim analysis because disease-free survival was longer with chemotherapy. With median follow-up of 59.2 months, 5-year disease-free survival was 38.7% with hepatectomy alone and 49.8% with chemotherapy (hazard ratio 0.67, 95% CI 0.50 to 0.92). Updated 5-year overall survival was 83.1% with hepatectomy alone and 71.2% with hepatectomy followed by chemotherapy. Grade 3 or higher neutropenia occurred in 50% of patients in the chemotherapy arm, and one patient died of unknown cause after three courses.", "program": "colorectal", "level": "clinical", "by": "Claude", "added": "2026-10-30", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-T-DABTHY", "trial": "T-DABTHY", "papers": [ { "key": "P-T-DABTHY22", "pmid": "35658604", "title": "Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial.", "journal": "Thyroid", "year": "2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35658604/", "doi": "10.1089/thy.2022.0115", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "A small phase 2 trial with a modified response definition that counts minor responses; it was not powered to show small differences. The abstract does not report progression-free or overall survival. It does not compare either regimen with lenvatinib or other standard treatment, and it says nothing about anaplastic carcinoma.", "label": "Dabrafenib versus dabrafenib plus trametinib in BRAF-mutated radioiodine-refractory thyroid cancer", "kind": "rct", "result": "negative", "setting": "Open-label randomized phase 2 multicenter trial; primary endpoint objective response by modified RECIST (including minor response) within the first 24 weeks", "population": "Adults with BRAF-mutated radioactive iodine refractory differentiated thyroid cancer and progressive disease within 13 months before enrollment; 53 patients enrolled", "claim": "The objective response rate by modified RECIST was 42% (11/26) with dabrafenib versus 48% (13/27) with dabrafenib plus trametinib (p = 0.67). By standard RECIST 1.1 it was 35% (9/26) versus 30% (8/27). There were no treatment-related deaths.", "program": "thyroid", "level": "clinical", "by": "Claude", "added": "2026-10-30", "trialRecord": { "key": "T-DABTHY", "nct": "NCT01723202", "acronym": null, "title": "Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer", "status": "COMPLETED", "phases": [ "PHASE2" ], "enrollment": 53, "sponsor": "Bhavana Konda", "sponsorClass": "OTHER", "collaborators": [ "National Comprehensive Cancer Network" ], "hasResults": true, "start": "2012-11-07", "lastUpdate": "2025-08-24", "url": "https://clinicaltrials.gov/study/NCT01723202" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-NabDDHR26", "trial": "B-NabDDHR", "papers": [ { "key": "P-NabDDHR26", "pmid": "43003936", "title": "Dose-dense neoadjuvant bi-weekly nab-paclitaxel followed by epirubicin-cyclophosphamide versus bi-weekly docetaxel followed by epirubicin-cyclophosphamide in patients with HR+/HER2- early breast cancer: a multicentre, randomised, phase III trial.", "journal": "Breast Cancer Res Treat", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/43003936/", "doi": "10.1007/s10549-026-08091-4", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [ "B-HRPOS" ], "limits": "The positive residual-burden endpoint does not establish a survival benefit, survival equivalence, or cure. The abstract does not quantify high-grade neuropathy by arm. The publication describes a phase III study with 388 enrolled. The ClinicalTrials.gov snapshot instead lists phase 4 and an estimated enrollment of 100. The article calls August 21, 2019 its registration date; ClinicalTrials.gov lists that as the study start and lists December 2, 2019 as the first public posting. The study phase, enrollment and outcome time frames have not been reconciled. The abstract and publisher landing page were read, but the full methods, protocol amendments and analysis plan were not accessible. The direction of the reported DFS hazard ratio is not resolved by the abstract. These reporting discrepancies remain open, without a claim of misconduct.", "label": "Dose-dense nab-paclitaxel versus docetaxel in HR-positive early breast cancer", "program": "breast", "kind": "rct", "level": "clinical", "result": "mixed", "setting": "Neoadjuvant dose-dense taxane followed by epirubicin and cyclophosphamide", "population": "HR-positive/HER2-negative early breast cancer in Chinese hospitals", "claim": "The report enrolled 388 participants, 194 per arm. RCB 0/I was 20.1% with nab-paclitaxel versus 11.34% with docetaxel (P=0.018), while pCR was 15.98% versus 10.31% (P=0.098). Five-year DFS was 90.21% versus 87.11% (P=0.656) and OS was 96.34% versus 95.31% (P=0.274); neither survival comparison demonstrated superiority. Grade 3/4 adverse events were reported in 30% versus 38%, with grade 3/4 peripheral sensory neuropathy reported only in the nab-paclitaxel group.", "by": "Codex (GPT-6)", "added": "2026-11-12", "trialRecord": { "key": "B-NabDDHR", "nct": "NCT04182568", "acronym": null, "title": "Nab-paclitaxel Compared With Docetaxel Followed by Anthracyclines and Cyclophosphamide in the Neoadjuvant Breast Cancer", "status": "UNKNOWN", "phases": [ "PHASE4" ], "enrollment": 100, "sponsor": "Xijing Hospital", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2019-08-21", "lastUpdate": "2019-12-02", "url": "https://clinicaltrials.gov/study/NCT04182568", "retrievedAt": "2026-11-12T00:08:07.506416+00:00", "enrollmentType": "ESTIMATED", "firstPosted": "2019-12-02" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CRPMctDNA26", "trial": null, "papers": [ { "key": "P-CRPMctDNA26", "pmid": "43009710", "title": "Perioperative Circulating Tumor DNA Dynamics in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases.", "journal": "Ann Surg Oncol", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/43009710/", "doi": "10.1245/s10434-026-20869-w", "errata": [] } ], "pages": [], "targets": [], "biomarkers": [], "subtypes": [], "limits": "The full text specifies univariable Cox analyses, nonstandardized sampling and survival measured from surgery even when ctDNA was sampled later. Confounding, selection on test availability, differential surveillance and guarantee-time bias therefore require assessment. Different time-point denominators are not an unselected paired clearance cohort; a negative result does not rule out peritoneal disease. This cohort uses INTERCEPT measurements and must not be counted as independent replication of the parent cohort. A separate ongoing ctDNA-guided study is mentioned by the authors; this retrospective report does not establish benefit from ctDNA-guided surgery or therapy. No patient-level data were acquired or analyzed by RISCON.", "label": "Perioperative ctDNA after cytoreduction for colorectal peritoneal metastases", "program": "colorectal", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Retrospective single-center surgical cohort using a prospective ctDNA database", "population": "Selected patients undergoing cytoreductive surgery for colorectal peritoneal metastases with available perioperative ctDNA", "claim": "Among 87 patients, median follow-up was 26.2 months. ctDNA was detected before neoadjuvant therapy in 22 of 34, after neoadjuvant therapy and before surgery in 10 of 37, and after surgery in 30 of 83. Post-surgical positivity was associated with shorter recurrence-free survival (HR 3.5, 95% CI 2.1-5.9) and overall survival (HR 6.7, 95% CI 2.3-19.7). The pre-surgical overall-survival association had HR 5.73 (95% CI 0.92-35.5; P=0.061), leaving that estimate inconclusive.", "by": "Codex (GPT-6)", "added": "2026-11-12", "trialRecord": null, "sources": 1, "corrections": 0, "analysisRecord": null }, { "id": "U-HER2CR26", "trial": "B-HER2CR", "papers": [ { "key": "P-HER2CR26", "pmid": "43014086", "title": "Ultra-sensitive MRD assessment in long-term complete responders to anti-HER2 therapy in HER2-positive metastatic breast cancer: initial results from HER2-CR study.", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/43014086/", "doi": "10.1016/j.esmoop.2026.108639", "errata": [] } ], "pages": [], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [ "B-HER2POS" ], "limits": "This cohort selects durable responders who survived and remained in response long enough to enroll. Assays were performed retrospectively and some enrolled patients were not evaluable. Repeated samples do not increase the number of independent patients. Negativity at available assessments leaves the interval between samples unobserved. There is no randomized continuation-versus-discontinuation comparison. The study does not establish safe treatment withdrawal, a negative predictive value for future progression, or cure.", "label": "HER2-CR: residual ctDNA in durable responders with metastatic breast cancer", "program": "breast", "kind": "observational", "level": "clinical", "result": "descriptive", "setting": "Prospective blood collection and retrospective ctDNA assay in long-term responders to anti-HER2 treatment.", "population": "Patients with HER2-positive metastatic breast cancer with complete or partial response maintained for at least two years on one anti-HER2 regimen, regardless of current treatment status.", "claim": "Of 48 enrolled patients, 37 were evaluable for ctDNA. Median follow-up after enrollment was 17.8 months. Thirty of the 37 evaluable patients (81%) were ctDNA-negative at every available assessment. One patient progressed despite persistent ctDNA negativity, with the last sample taken 6.8 months before progression.", "by": "Codex (GPT-6)", "added": "2026-11-13", "trialRecord": { "key": "B-HER2CR", "nct": "NCT06663787", "acronym": "HER2 CR", "title": "Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Patients Who Achieved Durable Response to Anti-HER2 Treatment", "status": "ACTIVE_NOT_RECRUITING", "phases": [], "enrollment": 50, "sponsor": "Nagoya City University", "sponsorClass": "OTHER", "collaborators": [], "hasResults": false, "start": "2024-04-01", "lastUpdate": "2026-05-13", "url": "https://clinicaltrials.gov/study/NCT06663787", "retrievedAt": "2026-11-13T00:12:10.854252+00:00", "enrollmentType": "ESTIMATED", "firstPosted": "2024-10-29" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-CA2098M4", "trial": "C-CA2098M4", "papers": [ { "key": "P-CA2098M4", "pmid": "43014085", "title": "Nivolumab and total neoadjuvant treatment for locally advanced rectal cancer: results of a phase II trial (CA209-8M4).", "journal": "ESMO Open", "year": "2026", "url": "https://pubmed.ncbi.nlm.nih.gov/43014085/", "doi": "10.1016/j.esmoop.2026.108617", "errata": [] } ], "pages": [], "targets": [ "PDCD1" ], "biomarkers": [], "subtypes": [], "limits": "The composite requires sustained clinical response for at least twelve months in the nonoperated group, whereas the surgical component uses pathology at resection. Clinical and pathological complete response are different measurements, and the groups were not randomized to surgery. The single-arm design cannot isolate nivolumab effects, establish a cure or show that avoiding surgery improves outcomes. The authors’ attribution of the fatal event does not establish its cause. The abstract does not supply randomized comparative recurrence or safety results.", "label": "CA209-8M4: nivolumab plus total neoadjuvant therapy for rectal cancer", "program": "colorectal", "kind": "single-arm", "level": "clinical", "result": "mixed", "setting": "Total neoadjuvant treatment with chemoradiation followed by chemotherapy and nivolumab for locally advanced rectal cancer.", "population": "Patients in a single-group phase II study of locally advanced rectal cancer, predominantly with microsatellite-stable tumors.", "claim": "Of 29 enrolled patients, 28 were evaluable for the composite response endpoint. The reported 67.9% combined pathological complete response in 6 of 15 operated patients with sustained clinical complete response in 13 nonoperated patients. Grade 3 or higher adverse events during chemoimmunotherapy were reported in 51.7%, including one fatal event that the authors considered most likely related to unresolved chemoradiation toxicity.", "by": "Codex (GPT-6)", "added": "2026-11-13", "trialRecord": { "key": "C-CA2098M4", "nct": "NCT03921684", "acronym": null, "title": "Trial of Nivolumab With FOLFOX After Chemoradiation in Rectal Cancer Patients", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 29, "sponsor": "Baruch Brenner", "sponsorClass": "OTHER", "collaborators": [ "Bristol-Myers Squibb" ], "hasResults": false, "start": "2019-04-10", "lastUpdate": "2026-01-05", "url": "https://clinicaltrials.gov/study/NCT03921684", "retrievedAt": "2026-11-13T00:12:13.982523+00:00", "enrollmentType": "ACTUAL", "firstPosted": "2019-04-19" }, "sources": 2, "corrections": 0, "analysisRecord": null }, { "id": "U-UCI1467", "trial": "B-UCI1467", "papers": [], "pages": [ { "key": "uci-14-67-posted-results-20261112", "title": "UCI 14-67: first posted ClinicalTrials.gov results", "url": "https://clinicaltrials.gov/study/NCT02436993?tab=results", "file": "data/sources/pages/uci-14-67-posted-results-20261112.txt" } ], "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "subtypes": [], "limits": "Treatment allocation followed HER2 status, so disease biology and the assigned agents both differ. The reported PFS estimates describe separate cohorts and cannot establish comparative drug benefit. The PFS analysis populations differ from the enrolled cohorts. The posted complete response and designated toxicity outcomes have descriptions but no numerical results. The separately reported adverse-event module does not establish treatment attribution of deaths. The exact-ID PubMed search found no linked paper.", "label": "UCI 14-67: first posted neoadjuvant results by HER2 status", "program": "breast", "kind": "registry", "level": "clinical", "result": "descriptive", "setting": "Phase II preoperative chemotherapy with different added agents assigned according to HER2 status.", "population": "Patients with breast cancer in two prospectively assigned, nonrandomized cohorts defined by HER2 status.", "claim": "The first registry posting reports 2-year PFS of 68.2% (95% CI 51.7–84.7; 70 analyzed) in the HER2-negative cohort assigned bevacizumab and 90.3% (95% CI 81.1–99.5; 47 analyzed) in the HER2-positive cohort assigned trastuzumab and pertuzumab. Both cohorts received chemotherapy.", "by": "Codex (GPT-6)", "added": "2026-11-13", "trialRecord": { "key": "B-UCI1467", "nct": "NCT02436993", "acronym": null, "title": "Phase II Breast Ca Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab or Bevacizumab", "status": "ACTIVE_NOT_RECRUITING", "phases": [ "PHASE2" ], "enrollment": 120, "sponsor": "University of California, Irvine", "sponsorClass": "OTHER", "collaborators": [], "hasResults": true, "start": "2015-04", "lastUpdate": "2026-11-12", "url": "https://clinicaltrials.gov/study/NCT02436993", "retrievedAt": "2026-11-13T00:12:13.298624+00:00", "enrollmentType": "ACTUAL", "firstPosted": "2015-05-07" }, "sources": 2, "corrections": 0, "analysisRecord": null } ], "pairs": [ { "id": "QP-01", "program": "gxb", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G", "BM-HER2-B" ], "units": [ "U-A1", "U-ToGA", "U-GATSBY" ], "asOf": "2026-09-30", "status": "판단 기록됨", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "title": "유방암 HER2 근거를 위암에 어디까지 쓸 것인가", "question": "유방암에서 축적된 HER2 관련 근거를 위암 연구의 출발점으로 어디까지 활용할 수 있는가?", "judgment": "표적의 존재와 작용 기전까지는 공유 자산으로 쓰되, 약제 계열의 효과는 위암에서 따로 확인된 것만 인정한다. 구조 근거는 이식하고 임상 결론은 이식하지 않는다.", "basis": [ { "claim": "HER2 세포외 영역과 항체 결합 구조는 암종과 무관한 단백질 수준의 근거다.", "units": [ "U-HER2Fab", "U-HER2Pert" ] }, { "claim": "같은 표적에서도 약제 계열별 결과가 두 암종에서 갈렸다. 트라스투주맙과 T-DXd는 위암에서 생존을 늘렸고, T-DM1·퍼투주맙·라파티닙은 늘리지 못했다.", "units": [ "U-ToGA", "U-DG04", "U-GATSBY", "U-JACOB", "U-LOGiC", "U-TyTAN" ] }, { "claim": "HER2 양성 판정 기준 자체가 위암용으로 따로 만들어졌다.", "units": [ "U-Hofmann08", "U-GEAHER2" ] }, { "claim": "자체 분석 A1에서는 ERBB2 증폭군의 공동증폭 비율이 위암 46.6% 대 유방암 7.3%였다. 별도 위암 자료의 CV-A1은 같은 방향을 지지했지만, 새로운 EGC-MSK 위암 자료의 CV-A3은 3/26 대 재사용 METABRIC 비교군 42/298로 판단 불가였다. 두 외부 평가는 유방암 비교군을 공유하며 측정 플랫폼과 암종의 영향을 분리하지 못하므로, 암종 전체의 보편적 차이나 치료 반응으로 확대하지 않는다.", "units": [ "U-A1" ] } ], "objection": "T-DXd는 두 암종에서 모두 성공했으므로, 실패한 세 약제가 약제 설계 문제였을 뿐 암종 차이가 아니라는 해석도 가능하다. 이 해석을 배제할 근거는 아직 없다.", "changesMind": "유방암에서 먼저 성공한 약제가 위암에서도 같은 방향으로 재현된 사례가 셋 이상 쌓이면, 계열 효과의 이식 가능성을 근거 등급을 낮춘 형태로 인정한다.", "next": [ "실패한 세 약제와 성공한 두 약제를 전달 방식(항체·ADC·TKI)으로 갈라 표로 만든다", "ERBB2 증폭 수준이 약제별로 다르게 요구되는지 확인한다" ], "holdStatus": "not_flagged" }, { "id": "QP-02", "program": "gxb", "targets": [ "PIK3CA", "ESR1" ], "biomarkers": [], "units": [ "U-A3", "U-AF3" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "구조 신뢰도만으로 표적 순위를 정하는가", "question": "구조예측 신뢰도는 높지만 암종별 기능 근거가 부족한 표적을 우선 검토 대상으로 올릴 것인가?", "judgment": "올리지 않는다. 구조 신뢰도는 그 좌표를 계산으로 다룰 수 있다는 뜻일 뿐이고, 질환 관련성과는 다른 축이다. 우선순위는 질환 관련성이 있는 표적 안에서 구조 근거로 가른다.", "basis": [ { "claim": "PI3Kα의 예측 평균 신뢰도는 92.4로 이 목록에서 가장 높지만, 임상 근거는 구조가 아니라 PIK3CA 변이 선별에서 나왔다.", "units": [ "U-SOLAR1", "U-INAVO120" ] }, { "claim": "ERα는 예측 신뢰도 낮은 잔기가 46.4%인데도 실험 구조 493건과 3상 근거를 갖췄다.", "units": [ "U-ERago", "U-EMERALD" ] }, { "claim": "예측 모델은 단일 정적 구조를 내고, 리간드 결합 상태에 따른 형태 변화를 그대로 담지 않는다.", "units": [ "U-AF3" ] } ], "objection": "기능 근거가 없는 표적은 아무도 보지 않아서 없는 것일 수 있다. 구조로만 먼저 훑는 탐색을 아예 막으면 새 표적이 나오지 않는다.", "changesMind": "구조 근거만으로 시작해 기능 검증까지 도달한 사례를 이 라이브러리 안에서 확인하면, 탐색 트랙을 따로 만들어 준다.", "next": [ "표적마다 준비도 다섯 축을 따로 표시하고 합산하지 않는다", "질환 관련성 없는 후보는 Evidence Gaps 로 보내 필요한 자료를 적는다" ], "holdStatus": "not_flagged" }, { "id": "QP-03", "program": "gxb", "targets": [], "biomarkers": [ "BM-CLDN18", "BM-PDL1-CPS", "BM-PDL1-TAP" ], "units": [ "U-KN061", "U-IMP131", "U-DB03", "U-DG04" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "치료 반응 비교 전에 환자군 차이부터 맞춤", "question": "치료 반응이 서로 다르게 보고된 연구를 나란히 놓기 전에 어떤 환자군 차이를 먼저 확인해야 하는가?", "judgment": "넷을 먼저 맞춘다. 바이오마커 판정 기준, 치료 차수, 이전 치료 이력, 그리고 비교 대상이 된 대조군이다. 이 넷이 다르면 수치를 같은 축에 올리지 않는다.", "basis": [ { "claim": "CLDN18.2 양성 기준이 항체 연구와 세포치료 연구에서 서로 다르다.", "units": [ "U-SPOTLIGHT", "U-CT041" ] }, { "claim": "같은 약제라도 차수가 바뀌면 결과가 뒤집혔다. 펨브롤리주맙은 1차에서 생존을 늘렸고 2차에서는 늘리지 못했다.", "units": [ "U-KN859", "U-KN061" ] }, { "claim": "대조군이 다르면 같은 방향의 결과도 크기를 비교할 수 없다. T-DXd는 한 연구에서 의사 선택 항암제와, 다른 연구에서 라무시루맙 병용과 비교됐다.", "units": [ "U-DG01", "U-DG04" ] }, { "claim": "동반 항암제가 다른 두 연구에서 같은 바이오마커 집단의 결과가 갈렸다.", "units": [ "U-IMP130", "U-IMP131" ] }, { "claim": "트라스투주맙 데룩스테칸 연구를 암종 간 순위로 묶을 수 없다. 유방암 연구는 트라스투주맙과 탁산 치료 후 인간 표피성장인자 수용체 2 양성 전이성 유방암에서 트라스투주맙 엠탄신을 대조군으로 삼았다. 위암·위식도접합부 연구는 트라스투주맙 치료 후 진행 뒤 생검으로 인간 표피성장인자 수용체 2 양성이 확인된 2차 치료 환자에서 라무시루맙과 파클리탁셀 병용을 대조군으로 삼았다. 유방암 연구의 초기 중앙 판독 무진행생존 결과와 이후 연구자 판독 무진행생존 결과는 판독 주체와 기준일을 함께 적어야 한다.", "units": [ "U-DB03", "U-DG04" ] } ], "objection": "기준을 다 맞추면 비교할 짝이 거의 남지 않는다. 느슨하게 묶어 경향을 보는 편이 실용적이라는 주장도 가능하다.", "changesMind": "기준이 다른 연구들 사이에 일치율을 잰 연구가 나오면, 그 일치율을 달아 같은 축에 올린다.", "next": [ "Contradiction Board 의 각 짝에 이 넷을 칸으로 둔다", "CPS 와 TAP 점수의 일치율 연구를 찾는다", "비교표에 대조군과 판독 주체와 기준일 칸을 둔다" ], "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; source-checked and integrated by Codex (GPT-6)", "by": "Claude · 보완 Muse Spark1.3", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-04", "program": "breast", "targets": [ "CDK4/6", "ERBB2" ], "biomarkers": [], "units": [ "U-PALLAS", "U-GATSBY", "U-RINDBeRG" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "상충 결과가 나왔을 때 가설을 보류함", "question": "유망한 가설과 상충하는 결과가 나왔을 때 어떤 조건에서 보류하거나 기각할 것인가?", "judgment": "일차 평가변수 개선을 입증하지 못하면 해당 가설의 채택을 보류하고, 대상군·중재·비교중재를 명시해 연구 우선순위를 재검토한다. 실패 횟수만으로 자동 기각하거나 약제 계열 전체로 결론을 확대하지 않는다. 설계의 비교 가능성, 효과 추정의 정밀도와 비뚤림을 함께 평가하고, 편익이 입증되지 않은 것과 효과가 없음을 입증한 것을 구분한다.", "basis": [ { "claim": "팔보시클립 보조요법은 두 연구에서 각각 실패했다. 같은 계열의 다른 두 약제는 성공했으므로 계열 효과로 설명되지 않는다.", "units": [ "U-PALLAS", "U-PENELOPEB", "U-monarchE", "U-NATALEE" ] }, { "claim": "위암 HER2에서도 실패가 셋 누적됐다. 전달 방식이 다른 세 약제였다.", "units": [ "U-GATSBY", "U-JACOB", "U-LOGiC" ] }, { "claim": "위암의 1차 병용시험에서 연구자 평가를 이용한 일차 무진행생존은 개선됐지만, 중앙 독립 영상 재평가의 민감도 분석은 그 차이를 뒷받침하지 않았다. 이차 전체 생존의 개선도 입증되지 않았다. 평가자와 평가변수를 구분하지 않은 채 시험 전체를 성공이나 실패로 단순화하지 않는다.", "units": [ "U-RAINFALL" ] }, { "claim": "라무시루맙 불응성 진행 후 라무시루맙 병용은 일차 평가변수인 전체 생존 개선을 입증하지 못했고, 이차 무진행생존 개선만으로 전체 생존 편익을 단정할 수 없다. 위험비와 유의확률은 출처별 불일치가 정정으로 해소되지 않아 사용하지 않는다. 효능분석집단은 무작위배정 전체가 아니며 선별된 사후 연령 비교는 동등성 근거가 아니다.", "units": [ "U-RINDBeRG" ] } ], "objection": "보류 기준을 설계 차이로 설명 가능한지에 두면, 사후 설명을 만들어 실패를 계속 유예할 수 있다.", "changesMind": "보류한 가설이 설계를 고친 연구에서 재현되면 되살린다. 유예 사유는 연구 시작 전에 적어 둔 것만 인정한다.", "next": [ "Negative Findings 에 실패를 전달 방식별로 적는다", "CDK4/6 억제제 보조요법 네 연구(팔보시클립 두 연구, 아베마시클립과 리보시클립 각 한 연구)의 대상군과 평가 시점 차이를 표로 만든다", "출처 간 수치 불일치의 정정 여부와 추정대상을 확인한 뒤 해석을 확정한다." ], "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; source-checked and integrated by Codex (GPT-6)", "by": "Claude · 보완 Muse Spark1.3", "added": "2026-09-28", "holdStatus": "held" }, { "id": "QP-05", "program": "gxb", "targets": [], "biomarkers": [], "units": [ "U-A1", "U-A2", "U-A3", "U-A5" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "새 분석과 재현 중 무엇을 먼저 할 것인가", "question": "새로운 분석을 시작하는 것과 기존 공개 분석을 독립적으로 재현하는 것 중 무엇을 먼저 할 것인가?", "judgment": "계산 절차의 재현과 별도 환자군의 평가를 구분해, 실제 판단에 인용한 관찰부터 검증한다. 완료한 검증의 범위와 남은 불확실성을 기록하고 새 자료·코드·질문에 이전 검증을 자동 적용하지 않는다.", "basis": [ { "claim": "자체 분석 A1과 A3의 계산 재현은 완료됐다. 이는 고정 입력과 계산 결과를 확인한 기록이며 별도 환자군의 생물학적 결과를 새로 확인한 것은 아니다.", "units": [ "U-A1", "U-A3" ] }, { "claim": "A1의 별도 위암·유방암 코호트 평가는 공동증폭의 비교 방향을 지지했다. 위암의 증폭군이 작고 측정 플랫폼이 달라 치료 반응이나 인과 기전까지 입증하지는 못했다.", "units": [ "U-A1" ] }, { "claim": "A2의 외부 코호트 평가는 판단 불가였고, A5는 같은 수집 자료에 적용한 새로운 짝지은 관찰 분석이다. 이를 독립 검증 성공으로 합산하지 않는다.", "units": [ "U-A2", "U-A5" ] } ], "objection": "새 자료에서도 방향이 같으면 신뢰는 높아질 수 있다. 그러나 표본이 작거나 검체 분류와 측정 조건이 다르면 방향의 일치만으로 일반화할 수 없다.", "changesMind": "더 큰 별도 환자군에서 비교 가능한 검체·측정 기준과 사전 정의한 분석을 적용해 불확실성이 줄면 해당 관찰의 판단을 갱신한다. 계산 결과가 달라지면 원자료와 구현부터 재점검한다.", "next": [ "추가 위암 코호트의 환자 중복과 유전자 검사 범위를 확인한다", "ESR1 외부 평가의 표본 크기와 검체 분류 한계를 보완할 자료를 찾는다" ], "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "not_flagged" }, { "id": "QP-06", "program": "gastric", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G", "BM-HER2HET", "BM-pERBB2" ], "units": [ "U-GASTHER3", "U-DG04" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "2차 치료 비교 전에 HER2를 다시 재는가", "question": "위암에서 1차 항HER2 치료 후 2차 치료를 비교할 때, 진행 후 다시 측정한 HER2 상태를 기준으로 삼아야 하는가?", "judgment": "삼아야 한다. 진행 후 재측정을 요구한 연구와 요구하지 않은 연구를 같은 집단으로 묶지 않는다. 재측정 여부를 근거 단위마다 칸으로 남긴다.", "basis": [ { "claim": "1차 치료 후 HER2 양성을 잃은 비율이 29.1%로 보고됐다.", "units": [ "U-GASTHER3" ] }, { "claim": "다른 소규모 관찰에서도 32%에서 양성 소실이 보고됐다.", "units": [ "U-HER2loss16" ] }, { "claim": "종양 내 이질성이 기준 시점 2.9%에서 2차 생검 21.9%로 올라갔다.", "units": [ "U-GASTHER3" ] }, { "claim": "실제로 두 연구가 진행 후 생검으로 중앙 확인을 요구했다. 등록 기준에 그 문장이 있다.", "units": [ "U-DG02", "U-DG04" ] } ], "objection": "재생검이 어려운 환자가 많아 재측정을 요구하면 대상군이 선택적으로 좁아진다. 좁아진 집단의 결과를 전체에 적용하기 어렵다.", "changesMind": "혈액 검사가 조직 판정을 대신할 수 있다는 근거가 쌓이면 기준을 혈액으로 옮긴다. 현재 일치율은 64%다.", "next": [ "근거 단위마다 재측정 요구 여부 칸을 채운다", "혈액 ERBB2 증폭과 조직 판정의 일치율 연구를 더 찾는다" ], "holdStatus": "not_flagged" }, { "id": "QP-07", "program": "gastric", "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "units": [ "U-SPOTLIGHT", "U-CT041" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "판정 기준이 다른 두 대상군을 합치지 않음", "question": "CLDN18.2 양성 기준이 연구마다 다를 때 두 연구의 대상군을 같은 집단으로 다룰 것인가?", "judgment": "다루지 않는다. 판정 기준을 근거 단위의 본문에 적고, 기준이 다른 연구는 지도에서 같은 점으로 합치지 않는다. 두 기준의 일치율이 측정되더라도 그것만으로 같은 환자군이나 같은 치료 효과가 입증되는 것은 아니므로 자동으로 합치지 않는다.", "basis": [ { "claim": "항체 연구는 종양세포 75% 이상에서 중등도 이상의 막 염색을 요구했다.", "units": [ "U-SPOTLIGHT" ] }, { "claim": "세포치료 연구는 염색 강도 2+ 이상, 양성 세포 40% 이상을 기준으로 했다.", "units": [ "U-CT041" ] }, { "claim": "두 기준의 일치율을 직접 평가한 자료는 이 판단의 근거로 아직 연결하지 않았다.", "units": [] } ], "objection": "기준이 달라도 둘 다 같은 단백질을 본다. 임계값 차이를 과장하면 비교가 불가능해진다는 반론이 가능하다.", "changesMind": "같은 검체에서 판정 기준·검사법의 일치도와 불일치 사례를 평가하고, 대상군·치료 차수·중재·평가변수의 비교 가능성까지 확인한 자료가 확보되면 허용할 비교 범위를 다시 판단한다. 일치율만으로 환자군이나 치료 효과의 동등성을 인정하지 않는다.", "next": [ "판정 기준을 Biomarker Atlas 의 CLDN18.2 항목에 두 줄로 적는다", "기준 간 일치율 연구를 검색 대기 목록에 넣는다" ], "updated": "2026-09-30", "updatedBy": "Muse Spark1.3 draft; Codex source correction; Gemini Flash3.8 review", "by": "Claude · 보완 Muse Spark1.3·Codex", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-08", "program": "breast", "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "units": [ "U-PADA1", "U-SERENA6", "U-A2", "U-A5" ], "asOf": "2026-11-07", "status": "판단 기록됨", "title": "진행 전 교체의 이득을 무엇으로 셀 것인가", "question": "ESR1 변이가 영상 진행보다 먼저 혈액에서 잡혔을 때 치료를 바꾸는 전략의 이득을 무엇으로 평가할 것인가?", "judgment": "동일한 진행 전 선별 조건에서 무작위 비교한 치료 교체 전략의 무진행생존 이득은 인정한다. 전체 생존·후속 치료 결과·위해는 각각의 공개 근거에 따라 따로 판단하며, 조직의 변이 검출 차이만으로 교체 전략의 효과나 변이 획득 원인을 설명하는 판단은 보류한다.", "basis": [ { "claim": "혈액에서 ESR1 변이가 검출됐지만 영상 진행이 없는 환자에서 치료를 교체한 두 무작위 연구는 각 비교군에 비해 무진행생존 개선을 보고했다.", "units": [ "U-PADA1", "U-SERENA6" ] }, { "claim": "같은 교체 시험의 확장 분석에서 두 번째 무진행생존은 25.7개월 대 19.1개월(위험비 0.63)이었다. 전체 생존은 아직 보고되지 않았다.", "units": [ "U-SERENA6" ] }, { "claim": "환자를 짝짓지 않고 원발·전이 표본군을 비교한 A2와 같은 환자의 검체를 짝지은 A5는 검출 양상의 관찰이다. 선택한 검체의 순서와 치료 노출이 달라 변이의 획득이나 치료 효과를 직접 검증하지 않았다.", "units": [ "U-A2", "U-A5" ] }, { "claim": "A2의 별도 수집 코호트 평가는 같은 방향의 점추정치를 보였지만 불확실성 때문에 판단 불가로 남았다. 혈액을 이용한 치료 교체 시험과 조직 검체의 비교는 같은 평가변수가 아니다.", "units": [ "U-A2" ] } ], "objection": "전체 생존이 미확정이라는 이유만으로 이미 확인된 무작위 비교의 무진행생존 이득을 부정할 수는 없다. 반대로 그 이득을 장기 생존이나 모든 검사·치료 조합에 일반화할 수도 없다.", "changesMind": "같은 시험의 성숙한 전체 생존, 후속 치료 이후 결과, 삶의 질과 위해가 공개되면 각 평가변수의 판단을 갱신한다. 관찰 분석의 방향만으로 임상 결론을 대신하지 않는다.", "next": [ "치료 교체 시험의 후속 생존·위해 보고를 원래 근거 단위에 연결한다", "검체와 측정 조건을 맞춘 더 큰 별도 환자군에서 ESR1 관찰을 평가한다" ], "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-09", "program": "gastric", "targets": [ "PDCD1", "CD274" ], "biomarkers": [ "BM-PDL1-CPS", "BM-PDL1-TAP" ], "units": [ "U-CM649", "U-RAT305" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "PD-L1 점수는 서로 바꿔 쓸 수 있는가", "question": "약제마다 다른 PD-L1 점수 체계(CPS, TAP)로 정한 대상군을 같은 기준선에서 비교할 수 있는가?", "judgment": "CPS와 TAP을 같은 기준선으로 취급하지 않는다. PD-L1 발현 점수의 선별·분석 역할과 각 약제의 결합 표적을 구분한다. 지도에서는 점수 체계와 절단값을 구분해 두며, 같은 숫자라고 같은 대상군으로 해석하지 않는다.", "basis": [ { "claim": "CheckMate 649는 PD-L1 발현과 무관하게 환자를 모집했으며, 니볼루맙 병용의 일차 전체 생존·무진행생존 비교는 CPS 5 이상 집단에서 평가했다.", "units": [ "U-CM649" ] }, { "claim": "RATIONALE-305는 PD-L1 발현과 무관하게 환자를 모집했으며, 일차 전체 생존을 TAP 5% 이상 집단과 무작위배정 전체 집단에서 각각 평가했다.", "units": [ "U-RAT305" ] }, { "claim": "위암의 니볼루맙·펨브롤리주맙 연구에서는 PD-1을 표적으로 하며 PD-L1 발현은 분석 지표로 쓰인다. 반면 유방암 IMpassion130의 아테졸리주맙은 PD-L1을 표적으로 한다. 선별·분석 지표와 약물 표적의 역할은 구분하며, 이 표적 설명으로 암종별 치료 효과를 이식하지 않는다.", "units": [ "U-KN859", "U-IMP130" ] } ], "objection": "두 점수가 대부분의 환자에서 같은 방향을 가리킨다면 구분이 지나치게 엄격할 수 있다.", "changesMind": "같은 검체에서 CPS와 TAP의 일치도·불일치 사례를 평가하고 검사법·대상군·평가변수에 따른 비교 가능 범위를 확인한 자료가 확보되면 판단을 갱신한다. 일치율만으로 점수 체계나 치료 효과의 동등성을 인정하지 않는다.", "next": [ "Biomarker Atlas 에 점수 체계와 절단값을 칸으로 둔다", "점수 체계 간 일치율 연구를 찾는다" ], "updated": "2026-09-30", "updatedBy": "Muse Spark1.3 draft; Codex source correction; Gemini Flash3.8 review", "by": "Claude · 보완 Muse Spark1.3·Codex", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-10", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2LOW-B", "BM-HR" ], "units": [ "U-DB04", "U-DB06" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "HER2 저발현은 아형이 아니라 발현 수준임", "question": "HER2 저발현(low, ultralow)을 기존 유방암 아형과 나란한 새 아형으로 다룰 것인가, 아형을 가로지르는 속성으로 다룰 것인가?", "judgment": "속성으로 다룬다. 저발현은 HR 양성군과 삼중음성군 모두에 걸쳐 있다. 화면에서는 아형 축과 발현 수준 축을 따로 두고 겹치는 칸을 보여 준다.", "basis": [ { "claim": "저발현 연구 대상의 88.7%는 HR 양성이었고 나머지는 HR 음성이었다.", "units": [ "U-DB04" ] }, { "claim": "다른 연구는 HR 양성군에서 low 와 ultralow 를 함께 받았다.", "units": [ "U-DB06" ] }, { "claim": "판정 지침이 2023년에 개정됐다.", "units": [ "U-ASCOCAP23" ] } ], "objection": "치료 선택을 바꾸는 속성이라면 실무에서는 아형과 다름없이 쓰인다. 구분이 화면만 복잡하게 만든다는 반론이 가능하다.", "changesMind": "저발현 여부가 예후나 생물학에서 독립된 군을 이룬다는 근거가 나오면 아형 축에 올린다.", "next": [ "Breast Cancer 화면에 HR 상태 × HER2 발현 수준 행렬을 둔다", "HR 음성 · ultralow 칸의 근거가 비어 있음을 Evidence Gaps 에 올린다" ], "holdStatus": "not_flagged" }, { "id": "QP-11", "program": "breast", "targets": [ "ERBB2", "TACSTD2" ], "biomarkers": [], "units": [ "U-DB04", "U-TROPiCS02", "U-ADCLow", "U-ADCSequence84" ], "asOf": "2026-10-01", "status": "판단 기록됨", "title": "ADC를 이어 쓴 결과를 무엇으로 추정하는가", "question": "항체-약물 접합체를 차례로 쓰는 경우의 효과를 현재 라이브러리 근거로 추정할 수 있는가?", "judgment": "두 접합체를 모두 받은 환자들의 순차 사용 성적은 관찰 근거로 기록한다. 다만 순서가 무작위 배정되지 않았고 환자 구성과 이전 치료가 달라, 어느 순서가 생존을 늘리는지에 대한 인과 판단은 보류한다. 첫 약제보다 두 번째 약제의 성적이 짧다는 관찰만으로 약제 간 교차 내성이나 특정 순서의 우월성을 확정하지 않는다.", "basis": [ { "claim": "HER2 표적 ADC 와 TROP2 표적 ADC 가 각각 따로 3상에서 효과를 보였다.", "units": [ "U-DB04", "U-TROPiCS02", "U-TROPIONB01" ] }, { "claim": "새로 연결한 후향적 다기관 연구에서는 두 약제를 모두 투여받은 환자들의 두 번째 접합체 사용 성적을 보고했다. 호르몬 수용체 상태에 따라 먼저 사용한 약제가 크게 달랐으므로 순서별 수치를 같은 조건의 비교처럼 읽지 않는다.", "units": [ "U-ADCLow" ] }, { "claim": "별도의 후향적 다기관 연구는 첫 접합체보다 두 번째 접합체의 치료 실패까지 시간이 짧았다고 보고했다. 이 평가변수는 무진행생존과 같지 않으며, 첫 약제와 실제 진료 전체 생존의 연관성도 무작위 순서 비교의 효과 추정치가 아니다.", "units": [ "U-ADCSequence84" ] } ], "objection": "관찰 자료는 실제 순차 사용의 양상과 후속 연구 질문을 보여준다. 그러나 두 약제를 모두 받을 수 있었던 환자만 포함한 선택과 치료 차수·환자 구성의 영향을 충분히 분리하지 못하면 약제 순서의 효과로 돌릴 수 없다.", "changesMind": "순서를 직접 비교한 무작위 연구나 대상군·치료 차수·평가 시작 시점·교란 보정이 명확한 비교 관찰 연구가 들어오면 해당 범위의 판단을 갱신한다. 방법 절에서 확인한 평가변수 차이를 유지하고, 아직 검토하지 않은 정량적 안전성과 보충자료를 따로 확인한다.", "next": [ "프랑스 연구에서 추적 종료 시점에 생존하고 진행이 없는 환자를 제외했다는 문구의 의도와 실제 분석 처리를 확인한다", "두 연구의 정량적 안전성 결과와 보충자료, 교란 보정에 포함한 변수를 확인한다", "호르몬 수용체 상태와 이전 치료를 맞춘 순서 비교 연구를 찾고, 관찰 연관성을 최적 순서로 바꾸지 않는다" ], "updated": "2026-10-01", "updatedBy": "Codex (GPT-6)", "reviewedBy": "Muse Spark1.3 / Gemini Flash3.8", "holdStatus": "held" }, { "id": "QP-12", "program": "gxb", "targets": [], "biomarkers": [], "units": [ "U-AFServer", "U-AF3", "U-AFDB" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "예측 서버 출력을 자동 검색에 연결함", "question": "AlphaFold Server 에서 받은 예측을 표적 후보를 자동으로 거르는 검색 작업에 연결할 수 있는가?", "judgment": "연결하지 않는다. 서버 출력은 도킹이나 스크리닝 도구에 쓸 수 없고 비상업 용도로 한정된다. RISCON Labs 가 비상업 조건에 해당하는지도 확인되지 않았다. 서버는 개별 조회와 해석에만 쓴다.", "basis": [ { "claim": "EMBL-EBI 안내에 비상업 이용, 도킹·스크리닝 도구 사용 금지, 하루 30건 한도가 적혀 있다.", "units": [ "U-AFServer" ] }, { "claim": "AlphaFold 3 모델 가중치는 비상업 기관 또는 그 기관을 위한 비상업 이용에만 제공된다.", "units": [ "U-AF3" ] }, { "claim": "예측 데이터베이스 조회는 이와 별개 기능이며 이 초안에서 실제로 연결돼 있다.", "units": [ "U-AFDB" ] } ], "objection": "연구 목적이면 비상업으로 볼 수 있다는 해석도 있다. 다만 판정 권한은 약관을 낸 쪽에 있다.", "changesMind": "RISCON Labs 의 법적 지위와 이용 목적이 약관상 비상업으로 확인되면 개별 예측 작업만 연다. 스크리닝 연결은 그와 무관하게 열지 않는다.", "next": [ "RISCON Labs 의 지위를 약관 조항에 맞춰 설립자이자 연구소장이 확인한다", "상업 이용이 가능한 다른 예측 도구의 라이선스를 검토한다" ], "holdStatus": "held" }, { "id": "QP-13", "program": "gastric", "targets": [ "CLDN18.2" ], "biomarkers": [ "BM-CLDN18" ], "units": [ "U-A3", "U-AFDB" ], "asOf": "2026-09-30", "status": "판단 기록됨", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6); Muse Spark1.3 and Gemini Flash3.8 review", "title": "동형을 가리지 않은 예측 모델은 쓰지 않음", "question": "CLDN18.2 를 볼 때 데이터베이스의 기본 CLDN18 예측 모델을 그대로 써도 되는가?", "judgment": "쓰지 않는다. 기본 항목은 동형 A1 이고 CLDN18.2 는 동형 A2 다. 두 서열은 1–69번 구간에서 21곳이 다르다. A2 전용 예측 항목과 2026년 실험 구조를 쓴다.", "basis": [ { "claim": "자체 분석 A3에서 두 동형은 길이가 같고 차이는 모두 1–69번 구간 안에 있으며 70번부터 같다. 정형 동형의 위상 주석에 따르면 1–69번 구간은 N-말단 세포질 분절(1–6번), 첫 막관통 나선(7–27번), 첫 세포외 영역(28–80번)의 대부분에 걸친다. 이 주석이 다른 동형에서도 유지되는지는 해당 계산으로 확인하지 않았다.", "units": [ "U-A3" ] }, { "claim": "데이터베이스에는 A2 전용 항목이 따로 있다. 두 항목의 평균 신뢰도는 비슷하다(72.81, 73.12).", "units": [ "U-AFDB" ] } ], "objection": "평균 신뢰도가 비슷하고 70번 이후가 같으므로, 전체 형태를 볼 때는 기본 모델도 충분하다는 반론이 가능하다.", "changesMind": "항체 접촉 부위가 70번 이후라는 사실만으로 기본 모델의 대체 사용을 허용하지 않는다. 검토할 구조의 동형과 서열, 접촉 부위의 대응이 직접 확인되고 해당 분석 목적에 필요한 구조적 대응이 뒷받침되면, 확인된 범위에서 다시 검토한다.", "next": [ "실험 구조에서 항체 접촉 잔기가 1–69번 구간에 드는지 표시한다", "실험 구조의 원논문 공개를 확인한다" ], "holdStatus": "not_flagged" }, { "id": "QP-14", "program": "gxb", "targets": [], "biomarkers": [], "units": [ "U-CT041", "U-A2", "U-Razavi18", "U-monarchE", "U-OlympiA", "U-SOFT", "U-ASTRRA", "U-ATLAS", "U-NSABPB42", "U-SALSA", "U-NATALEE" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "재발과 전이를 반응 연구와 떼어 관리하는가", "question": "초기 치료 반응 이후 남는 재발·전이 문제를 치료 반응 연구와 분리된 연구축으로 관리할 것인가?", "judgment": "분리한다. 진행성 암의 반응·진행을 평가하는 연구와 수술 뒤 재발을 예방하는 연구는 출발점과 평가변수가 다르다. 새 내분비요법 근거를 반영해 재발 예방 안에서도 항암치료 뒤 난소기능 억제를 추가하는 질문과 일정 기간 무질병 상태를 유지한 뒤 약제를 연장하는 질문을 나눈다. 무질병생존, 유방암 관련 사건, 전체 생존을 같은 결과로 합치지 않고 연구별 이득과 위해를 기록한다. 같은 시험의 장기 추적은 침윤성 무질병생존과 전체 생존을 나누어 한 시험으로 센다.", "basis": [ { "claim": "진행성 위암의 세포치료 연구는 진행을, 고위험 조기 유방암의 보조요법 연구는 침윤성 무질병생존 등을 비교한다. 진행성 질환의 성적을 수술 뒤 재발 예방 효과로 옮기지 않는다.", "units": [ "U-CT041", "U-monarchE", "U-OlympiA" ] }, { "claim": "폐경 전 내분비요법 시험은 항암치료 여부가 다른 집단을 포함한다. 별도의 한국 연구는 항암치료 뒤 난소기능이 유지되거나 회복된 환자를 선별했다. 두 연구의 대상과 억제 기간이 달라 수치를 나란히 두어 최적 기간을 정할 수 없다.", "units": [ "U-SOFT", "U-ASTRRA" ] }, { "claim": "타목시펜 연장 시험은 앞선 치료를 마친 뒤 계속 투여할지 비교했고, 수용체 양성 집단에서 후기 재발과 유방암 사망의 감소를 보고했다. 폐색전과 자궁내막암 위해는 함께 남긴다.", "units": [ "U-ATLAS" ] }, { "claim": "폐경 후 아로마타제 억제제 기반 치료를 마친 무질병 집단의 연장 시험은 초기 무질병생존 분석에서 보정된 유의수준을 충족하지 못했다. 후속 추적에서 같은 지표의 차이가 보고됐지만 전체 생존 개선은 입증되지 않았다. 후속 결과가 초기 판정과 사전 분석계획을 지우지는 않는다.", "units": [ "U-NSABPB42" ] }, { "claim": "서로 다른 환자의 원발·전이 검체를 비교한 계산에서는 수용체 유전자 변이 빈도가 달랐다. 이 관찰과 치료 노출에 따른 유전체 연관만으로 개별 환자에게 변이가 생긴 원인이나 재발 예방 전략의 효과를 확정할 수는 없다.", "units": [ "U-A2", "U-Razavi18" ] }, { "claim": "살사는 폐경 후 호르몬 수용체 양성 유방암에서 앞선 내분비요법 5년 뒤 아나스트로졸을 2년 더 쓰는 전략과 5년 더 쓰는 전략을 비교했다. 주분석은 연장치료 첫 2년 동안 재발 없이 연구에 남아 있던 환자부터 시작했다. 총 10년 전략은 총 7년보다 무질병생존 개선을 입증하지 못했고 임상 골절 위험은 더 높았다. 이는 처음 치료와 무치료의 비교가 아니며 유의하지 않은 차이를 동등성으로 바꾸지 않는다.", "units": [ "U-SALSA" ] }, { "claim": "호르몬 수용체 양성 조기 유방암 보조 병용요법 시험의 사전 계획된 5년 추적에서는 침윤성 무질병생존의 이득이 유지되었고 전체 생존은 아직 성숙 중으로 수치상 경향에 그쳐 생존 이득 확정으로 세지 않는다. 중간 분석과 최종 분석과 탐색적 추가 추적과 5년 추적은 같은 시험의 보고로 묶고 별개 시험으로 중복 계산하지 않는다.", "units": [ "U-NATALEE" ] }, { "claim": "유전성 변이 동반 고위험 조기 유방암 보조요법 시험에서는 두 번째 사전 계획 중간분석에서 전체 생존의 유의수준을 충족했고 세 번째 장기 추적은 기술적 갱신으로 지속 양상을 보여주되 새로운 확증 검정으로 세지 않는다. 침윤성 무질병생존과 전체 생존을 나누어 기록하고 같은 시험의 추적을 독립 재현으로 세지 않는다.", "units": [ "U-OlympiA" ] } ], "objection": "재발 예방과 진행성 질환이 생물학적으로 이어지므로 지나치게 나누면 공통 기전을 놓칠 수 있다. 그러나 모집 시점, 폐경 상태, 이전 치료와 평가변수가 다른 시험을 합치면 대상군 차이를 약효 차이로 오해한다. 같은 시험의 장기 추적이나 여러 연구축 연결은 근거를 중복 계산할 이유가 되지 않는다.", "changesMind": "같은 출발 조건과 평가변수로 전략을 직접 비교한 근거가 확보되면 구분을 조정한다. 생존·장기 위해 결과가 갱신되면 해당 시험의 판단을 고치되, 추적 보고를 별도 시험이나 독립 재현으로 세지 않는다.", "next": [ "재발 예방 근거에 모집 시점, 이전 내분비요법, 폐경 상태, 난소기능 확인 조건을 붙인다", "추적 시점별 평가변수와 분석계획을 보존하고 재발·생존·위해를 따로 갱신한다", "위암 복막 전이와 유방암 재발의 연구축을 유지하되 같은 근거의 연결은 한 번만 센다", "연장치료 연구의 무작위 배정 시점과 주분석 기준시점을 구분하고, 재발 관련 결과와 골절 등 장기 위해를 각각 확인한다", "사전 계획된 추적과 기술적 갱신을 구분해 침윤성 무질병생존과 전체 생존의 성숙도를 따로 확인한다" ], "updated": "2026-09-30", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "holdStatus": "not_flagged" }, { "id": "QP-15", "program": "gxb", "targets": [ "ERBB2", "TACSTD2" ], "biomarkers": [], "units": [ "U-DS8201pre16", "U-SGpre15" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "접합체의 작용과 표적 의존성을 구별함", "question": "표적 항체에 세포독성 약물을 연결한 접합체가 종양을 억제하면, 그 종양이 표적의 고유한 신호에 의존한다고 판단할 수 있는가?", "judgment": "접합체의 항종양 기능 근거로 인정하되 표적 신호에 대한 의존성과 구분한다. 항체가 약물 전달에 기여한 결과와 표적 자체를 억제한 결과를 같은 주장으로 묶지 않는다. 이번 전임상 자료로 접합체의 임상 사용 순서를 추정하는 판단은 보류한다.", "basis": [ { "claim": "허투 표적 접합체는 표적 발현에 따른 세포 증식 억제를 보였고 위암 모델에서 종양을 줄였다. 기존 접합체에 둔감한 이식 모델과 허투 발현이 낮은 일부 유방암 이식 모델에서도 활성이 보고됐다.", "units": [ "U-DS8201pre16" ] }, { "claim": "트롭투 표적 접합체는 사람 위암 이식 모델에서 비특이적 대조 접합체보다 큰 항종양 효과를 보였다. 유리 약물과 접합체에 노출된 세포에서 유사한 손상·세포사멸 신호가 관찰됐다.", "units": [ "U-SGpre15" ] } ], "objection": "전달 기능과 표적 신호 억제가 한 약제 안에서 함께 작동할 수 있으므로 둘을 지나치게 분리하면 관찰된 효과를 충분히 설명하지 못할 수 있다. 구분은 어느 한 기전이 없다는 판정이 아니다.", "changesMind": "약물 전달 효과를 구분한 비교 자료에 더해 표적의 유전적 변화가 종양 생존을 좌우한다는 독립된 근거가 연결되면, 해당 모델에 한해 신호 의존성도 별도로 기록한다. 순서 판단은 순서를 직접 비교한 자료가 들어올 때 다시 검토한다.", "next": [ "두 논문의 결합, 세포 손상, 종양 억제 관찰을 각각 어떤 대조군이 뒷받침하는지 정리한다", "표적 의존성 자료와 접합체 순서 비교 자료를 서로 다른 검색 과제로 유지한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "held" }, { "id": "QP-16", "program": "gastric", "targets": [ "CLDN18.2" ], "biomarkers": [], "units": [ "U-ZOLpre24", "U-A3" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "항체 기능으로 동형 판별을 대신하지 않음", "question": "클라우딘18.2 항체의 세포 사멸과 종양 억제 결과가 있으면, 분석에 쓰는 서열의 동형과 임상 염색 기준도 함께 확인된 것으로 볼 수 있는가?", "judgment": "볼 수 없다. 항체 기능, 서열의 동형, 임상 검사 기준은 각각 확인한다. 졸베툭시맙의 위암 모델 결과는 기능 근거에 추가하되 기본 서열을 해당 동형으로 대신 쓰거나 서로 다른 환자 선별 기준을 합치는 근거로 쓰지 않는다.", "basis": [ { "claim": "졸베툭시맙은 클라우딘18.2 양성 세포에서 항체 의존성과 보체 의존성 세포독성을 보였고, 위암 생쥐 모델에서 단독 또는 병용 항종양 활성이 보고됐다.", "units": [ "U-ZOLpre24" ] }, { "claim": "같은 전임상 연구에서 생쥐의 면역관문을 차단하는 항체와의 병용은 각 단독 투여보다 큰 종양 억제를 보였다. 이 결과가 관찰된 대상은 세포와 생쥐 모델이다.", "units": [ "U-ZOLpre24" ] }, { "claim": "저장된 서열 비교에서는 클라우딘18의 두 동형 사이에 차이가 확인됐다. 해당 계산은 서열 비교이며 항체 결합이나 임상 검사 일치율을 측정한 자료가 아니다.", "units": [ "U-A3" ] } ], "objection": "동형을 명시한 세포에서 기능이 관찰됐다면 그 동형을 연구하는 근거로는 충분하다는 반론이 가능하다. 다만 모델에 붙은 동형 이름이 별도로 불러온 구조 파일이나 환자 검사에도 그대로 적용되는지는 다른 확인 사항이다.", "changesMind": "기능 연구의 항원 서열과 검토할 구조의 서열이 직접 대응되는 자료가 확보되면 그 구조에 한해 연결을 인정한다. 임상 선별 기준을 합치는 판단은 같은 검체에서 두 기준의 일치율을 확인한 자료가 있을 때만 다시 연다.", "next": [ "항체 기능 근거에 모델의 항원 동형과 사용한 서열의 출처를 함께 연결한다", "구조 파일의 동형 확인과 임상 염색 기준 일치율 확인을 별도 과제로 남긴다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-17", "program": "breast", "targets": [ "AKT", "CDK4/6" ], "biomarkers": [], "units": [ "U-AZD5363pre12", "U-PD0332991pre09" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "억제제 감수성은 분자 맥락을 붙여 읽는다", "question": "일부 유방암 모델이 신호 경로나 세포주기 억제제에 반응했다는 결과를 같은 표적을 가진 모든 종양의 성질로 확대할 수 있는가?", "judgment": "확대하지 않는다. 반응한 모델과 반응하지 않은 모델의 분자 배경을 함께 기록한다. 경로 억제와 성장 억제를 구분하고, 모델에서 관찰한 감수성 연관성을 환자 선별 검사로 확정하는 판단은 보류한다.", "basis": [ { "claim": "에이케이티 억제제 연구에서는 피아이쓰리케이 촉매 소단위 또는 피텐 변이가 감수성과 관련됐고 라스 변이는 내성과 관련됐다. 유방암 유래 세포주에서 감수성이 상대적으로 자주 관찰됐으나 모든 모델이 반응한 것은 아니다.", "units": [ "U-AZD5363pre12" ] }, { "claim": "세포주기 억제제 연구에서는 일부 허투 증폭 세포를 포함한 에스트로겐 수용체 양성 관강형 세포가 더 민감했고 비관강형·기저형 세포는 더 저항적이었다. 민감한 세포에서는 세포주기 정지와 망막모세포종 단백질의 인산화 억제가 관찰됐다.", "units": [ "U-PD0332991pre09" ] } ], "objection": "여러 모델에서 같은 분자 특징과 반응이 연결되면 선별 가설을 세울 실용적 이유가 있다. 이를 확정된 기준으로 부르지 않는다는 이유로 탐색 가치까지 낮춰서는 안 된다.", "changesMind": "후보 특징을 미리 정한 독립 모델에서 민감군과 저항군의 구분이 재현되면 선별 가설의 근거를 보강한다. 환자 적용 판단은 검사 기준과 치료 결과를 함께 검증한 별도의 임상 자료가 들어오면 갱신한다.", "next": [ "반응군과 비반응군의 유전 배경, 수용체 상태, 측정한 평가변수를 같은 표에 기록한다", "세포주 간 연관성과 사람의 선별 검사 검증을 다른 근거 단계로 구분한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "held" }, { "id": "QP-18", "program": "breast", "targets": [ "PDCD1", "CD274" ], "biomarkers": [], "units": [ "U-PD1Rupp22", "U-PDL1Glyco16" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "면역 차단의 효과와 선별 점수를 나눔", "question": "면역관문 차단의 항종양 효과와 리간드 안정화 기전을 확인하면, 사람 종양의 염색 점수로 반응군을 고르는 기준도 뒷받침되는가?", "judgment": "기전 설명의 근거로 추가하되 환자 선별 기준의 검증으로 보지 않는다. 수용체 차단, 리간드의 단백질 조절, 임상 염색 점수는 각각 다른 관찰이다. 병용으로 얻은 모델의 효과를 어느 한 약제의 임상 효과로 돌리지 않는다.", "basis": [ { "claim": "면역 배경이 맞는 생쥐의 삼중음성 유방암 이식 모델에서 면역관문 차단 항체의 항종양 활성이 관찰됐고, 두 항체의 병용은 유방암 모델에서 활성을 높였다. 항체에 따라 종양 내 면역세포 환경의 변화는 달랐다.", "units": [ "U-PD1Rupp22" ] }, { "claim": "피디엘원 리간드의 당화는 단백질 분해와 면역 억제의 조절에 연결됐다. 기저형 유방암 맥락에서 성장인자 신호를 억제하자 리간드가 불안정해졌고 생쥐 모델에서 티세포 활성과 피디원 차단 효과가 강화됐다.", "units": [ "U-PDL1Glyco16" ] } ], "objection": "기전과 동물 반응이 같은 방향을 가리키면 검사 후보를 탐색하는 출발점으로 쓸 수 있다. 다만 후보를 만들 수 있다는 판단과 특정 점수의 절단값이 검증됐다는 판단은 같지 않다.", "changesMind": "동일한 사람 종양 검체에서 리간드 상태와 임상 검사 점수의 관계를 확인하고, 미리 정한 점수 기준으로 치료 결과를 검증한 자료가 연결되면 선별 근거를 별도로 추가한다.", "next": [ "각 동물 결과에 암종, 숙주의 면역 상태, 단독·병용 구성을 함께 표시한다", "리간드 당화나 안정성이 임상 염색 점수에 어떻게 반영되는지 직접 다룬 자료를 찾는다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-19", "program": "gastric", "targets": [ "FGFR2", "KDR" ], "biomarkers": [], "units": [ "U-FGFR2Xie13", "U-VEGFR2Mashima21" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "종양 축소만으로 작용 위치를 단정하는가", "question": "위암 이식 모델에서 약물로 종양이 억제됐을 때, 그 효과를 종양세포 자체의 표적 의존성과 숙주 혈관의 변화 가운데 어디에 귀속할 것인가?", "judgment": "종양 크기만으로 귀속하지 않는다. 증폭된 수용체의 유전적 억제가 암세포 성장을 바꾼 자료와 숙주 유래 혈관 신호를 차단한 자료를 나누어 기록한다. 두 결과의 효과 크기를 표적 우열의 공통 척도로 쓰지 않는다.", "basis": [ { "claim": "섬유아세포 성장인자 수용체가 증폭된 위암 모델에서는 약물 억제뿐 아니라 해당 유전자의 발현을 낮추는 접근에서도 성장 억제가 관찰됐다. 비증폭 모델에서는 같은 약물의 종양 성장 억제가 관찰되지 않았다.", "units": [ "U-FGFR2Xie13" ] }, { "claim": "혈관내피 성장인자 수용체 차단 연구에서는 위암 이식 생쥐의 혈중 성장인자가 증가했고 그 증가분은 숙주에서 유래했다. 성장인자를 함께 중화하자 수용체 항체 단독보다 항종양 효과가 커졌으며 혈관생성 억제와 관련된 변화가 관찰됐다.", "units": [ "U-VEGFR2Mashima21" ] } ], "objection": "종양세포와 숙주 혈관의 변화는 실제로 서로 영향을 주므로 작용 위치를 완전히 분리하기 어려울 수 있다. 구분은 상호작용을 부정하려는 것이 아니라 어떤 자료가 어느 부분을 직접 뒷받침하는지 밝히기 위한 것이다.", "changesMind": "서로 다른 모델에서 종양세포와 숙주의 기여를 구분한 결과가 재현되고 종양 억제와 연결되면 각 기전의 적용 범위를 넓힌다. 유전자 증폭과 단백질 발현을 같은 선별 조건으로 보는 판단은 별도의 대응 자료가 있을 때 검토한다.", "next": [ "위암 기능 근거마다 종양세포와 숙주 중 실제로 조절하거나 측정한 대상을 적는다", "증폭된 수용체의 유전적 의존성과 숙주 혈관 반응을 각각 독립 검증할 자료를 찾는다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "not_flagged" }, { "id": "QP-20", "program": "gxb", "targets": [ "ERBB2", "CD274" ], "biomarkers": [], "units": [ "U-FLOT4", "U-KATHERINE", "U-IMP030", "U-CREATEX", "U-EA1131", "U-ACTSGC", "U-JACCROGC07", "U-ARTIST2", "U-PRODIGY", "U-TOPGEAR", "U-ARTIST" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "수술 전후의 성적은 맥락을 맞춰 읽음", "question": "위암의 수술 전후 항암요법과 수술 후 보조요법, 선행치료 뒤 잔존 유방암의 보조요법, 수술부터 시행한 유방암의 보조요법 결과를 하나의 재발 방지 성적으로 비교할 수 있는가?", "judgment": "같은 성적으로 합치지 않는다. 암종과 아형, 수술 전 치료 여부, 잔존 질환에 따른 선별, 대조군, 평가변수를 먼저 기록한다. 각 무작위 연구 안에서 얻은 결론은 유지하되 연구 사이의 효과 크기로 치료의 우열을 매기는 판단은 보류한다.", "basis": [ { "claim": "원격 전이가 없는 절제 가능한 국소 진행 위암·위식도접합부암 연구에서는 도세탁셀 기반 수술 전후 병용요법이 비교 요법보다 전체 생존을 개선했다. 이 연구는 수술 후 치료만을 비교하거나 선행치료 뒤 잔존 질환만으로 대상을 고른 연구가 아니다.", "units": [ "U-FLOT4" ] }, { "claim": "일본의 2·3기 위암 연구에서는 확대 림프절 절제술을 포함한 수술 뒤 에스원을 투여한 군이 수술만 받은 군보다 전체 생존과 무재발생존에서 나은 결과를 보였다. 최초 보고와 5년 추적은 같은 무작위 시험의 결과이며, 다른 보조요법이나 수술 전후 전략과 직접 비교한 결과는 아니다.", "units": [ "U-ACTSGC" ] }, { "claim": "병리학적 3기 위암의 확대 림프절 절제술 뒤 에스원에 도세탁셀을 더한 군은 에스원 단독군보다 3년 무재발생존과 5년 전체 생존이 개선됐다. 그러나 3년 이후 늦은 재발의 비율은 비슷했다. 장기 보고는 같은 시험의 추적 결과이며, 정정문에서 고친 사건 수를 재발 환자 수로 바꾸어 읽지 않는다.", "units": [ "U-JACCROGC07" ] }, { "claim": "림프절 양성 2·3기 위암의 수술 후 세 요법 비교에서는 에스원 단독, 옥살리플라틴 병용, 여기에 방사선을 포함한 요법의 무질병생존을 평가했다. 옥살리플라틴 병용 두 군 사이에서 방사선 추가의 유의한 개선은 확인되지 않았지만, 이를 동등성이나 모든 방사선 전략의 무효로 읽지는 않는다.", "units": [ "U-ARTIST2" ] }, { "claim": "한국의 절제 가능한 국소 진행 위암·위식도접합부암 연구에서는 확대 림프절 절제술과 수술 후 에스원에 선행 도세탁셀·옥살리플라틴·에스원을 더한 전략이 일차 무진행생존을 개선했고, 장기 추적에서는 이차 평가변수인 전체 생존도 개선됐다. 배정 인원과 치료를 받은 전체 분석 집단은 다르며, 이 결과로 다른 수술 전후 요법보다 우수하다고 판단하지 않는다.", "units": [ "U-PRODIGY" ] }, { "claim": "절제 가능한 위암·위식도접합부암의 수술 전후 항암요법에 수술 전 화학방사선요법을 더한 연구에서는 병리학적 완전반응이 늘었지만 일차 전체 생존의 개선은 확인되지 않았다. 반응 상승을 생존 개선으로 대신 읽지 않으며, 후속 고령자 분석도 별개의 무작위 검증으로 세지 않는다.", "units": [ "U-TOPGEAR" ] }, { "claim": "확대 림프절 절제술 뒤 카페시타빈·시스플라틴에 방사선을 병용한 원래 아티스트 연구는 전체군 일차 무질병생존 개선을 보이지 않았고 장기 전체 생존에서도 차이를 입증하지 못했다. 두 군의 항암 노출도 달랐으므로 동일 항암요법에 방사선만 더한 비교로 단순화하지 않는다. 유리한 하위군은 전체군 음성 결과를 뒤집지 않으며, 아티스트 투는 별도의 시험이다.", "units": [ "U-ARTIST" ] }, { "claim": "선행 항암요법과 트라스투주맙 뒤 유방 또는 겨드랑이에 침윤성 병변이 남은 허투 양성 조기 유방암 연구에서는 트라스투주맙 엠탄신이 트라스투주맙보다 침윤성 무질병생존과 전체 생존을 개선했다. 저장된 보고는 전자의 최종 분석과 후자의 두 번째 중간 분석이다.", "units": [ "U-KATHERINE" ] }, { "claim": "수술을 첫 치료로 받은 2·3기 삼중음성 유방암 연구에서는 수술 후 항암요법에 아테졸리주맙을 더해도 침윤성 무질병생존이 개선되지 않았다. 무용성 중간 분석 뒤 약제 투여가 중단되고 예정 시점보다 이른 최종 분석이 이뤄졌다.", "units": [ "U-IMP030" ] }, { "claim": "허투 음성 잔존 침윤암에서 카페시타빈을 추가한 비교는 무질병생존과 전체 생존 개선을 보고했다. 잔존 삼중음성 암에서 카페시타빈 대신 백금계를 쓴 별도 연구는 비열등성을 입증하지 못했고 중증 독성이 더 많았다. 추가의 이득과 약제 대체의 타당성은 별도 질문이다.", "units": [ "U-CREATEX", "U-EA1131" ] } ], "objection": "이 연구들이 모두 재발과 사망을 줄이려는 수술 전후 치료 연구이므로 함께 검토할 가치는 있다. 다만 목적의 공통성이 대상군과 평가변수의 차이를 없애거나 한 연구의 성공·실패를 다른 상황에 그대로 옮길 근거가 되지는 않는다.", "changesMind": "같은 대상군과 평가변수로 치료 전략을 직접 비교한 결과가 공개되면 해당 맥락에서 상대 효과를 판단한다. 간접 비교는 대상군과 대조군의 연결 가능성을 검토한 자료가 있을 때 범위를 정해 다시 살핀다.", "next": [ "각 수술 전후 연구에 암종·아형, 림프절 절제 범위, 선행치료, 잔존 질환 선별과 대조군을 붙여 정리한다", "전체 생존과 침윤성 무질병생존을 나누고 최종·중간 분석 및 조기 중단 여부를 함께 기록한다", "선행 약제 추가와 수술 전·후 방사선 병용을 나누고, 병리 반응과 생존 평가변수의 결론이 같은지 따로 확인한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-21", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-ctDNAYang20", "U-ctDNAYuan23" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "재발 예측과 치료 이득을 따로 판정한다", "question": "위암 절제 뒤 혈중 순환 종양 유전물질이 재발 위험을 예측하면, 그 검사에 따라 치료를 바꾸는 전략이 생존을 늘린다고 볼 수 있는가?", "judgment": "재발 위험과의 연관성을 뒷받침하는 근거로 인정한다. 그러나 검사 결과에 따라 치료를 바꿨을 때 재발이나 사망이 줄어든다는 판단은 보류한다. 수술 직후와 보조항암요법 뒤의 검출은 측정 시점이 다른 관찰로 남긴다.", "basis": [ { "claim": "완치를 목적으로 절제한 일·이·삼기 위암의 전향적 코호트에서 수술 후 추적 중 순환 종양 유전물질 검출은 더 나쁜 무질병생존 및 전체 생존과 연관됐고, 영상으로 확인되는 재발에 앞선 검출도 보고됐다.", "units": [ "U-ctDNAYang20" ] }, { "claim": "절제 가능한 이·삼기 위암의 다른 전향적 코호트에서는 수술 후와 보조항암요법 후 검출이 각각 재발 위험과 연관됐다. 보조항암요법 뒤 잔존 신호는 해당 코호트에서 더 나은 재발 예측 성능을 보였다.", "units": [ "U-ctDNAYuan23" ] }, { "claim": "두 연구는 표지자 상태와 임상 경과를 관찰한 코호트다. 검사에 따라 치료를 바꾸는 전략과 바꾸지 않는 전략을 무작위로 비교해 재발이나 생존의 차이를 확인한 결과는 아니다.", "units": [ "U-ctDNAYang20", "U-ctDNAYuan23" ] } ], "objection": "독립된 전향적 코호트에서 위험 연관성이 반복되면 개입 연구의 대상을 정할 가치가 커진다. 다만 위험을 더 일찍 알게 된다는 사실만으로 그 뒤의 치료가 결과를 개선한다고 단정할 수는 없다.", "changesMind": "검사에 따른 개입 전략을 사전에 정하고 적절한 대조군과 비교해 재발·생존 및 위해를 평가한 결과가 확보되면 임상적 유용성을 별도로 판단한다. 검출률이나 위험 예측 성능의 개선만으로 이 판단을 바꾸지는 않는다.", "next": [ "각 코호트의 병기, 채혈 시점, 검사 방법, 보조치료 이력과 예측한 결과를 나누어 기록한다", "위험 연관성을 평가한 관찰 연구와 검사 기반 개입의 결과를 평가한 비교 연구를 별도 목록으로 관리한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "held" }, { "id": "QP-22", "program": "breast", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-cTRAKTN" ], "asOf": "2026-09-28", "status": "판단 기록됨", "title": "혈액 신호가 개입의 기회를 보장하는가", "question": "조기 삼중음성 유방암에서 혈중 순환 종양 유전물질을 검출하면, 영상으로 확인되는 전이 이전에 치료를 시작할 기회가 확보된 것으로 볼 수 있는가?", "judgment": "검출 자체가 개입 기회를 보장하지는 않는다. 검출 시점, 그때 시행한 병기 검사, 실제 개입에 도달한 인원을 따로 기록한다. 이 연구에서 드러난 실행 가능성의 제약은 인정하되 소수의 투여 결과만으로 약제의 재발 방지 효능이 확정적으로 실패했다는 판단은 보류한다.", "basis": [ { "claim": "선행항암요법 뒤 잔존 질환이 있는 조기 삼중음성 유방암 환자와 보조항암요법을 받은 이·삼기 환자를 포함한 연구에서 혈액 신호를 전향적으로 추적했다. 개입군에 배정된 검출 환자는 병기 검사를 받았고, 재발이 확인되지 않은 경우 펨브롤리주맙 투여를 제안받았다.", "units": [ "U-cTRAKTN" ] }, { "claim": "개입군으로 배정된 32명 가운데 23명은 신호 검출 시점의 병기 검사에서 이미 전이가 확인됐다. 이 분모는 전체 혈액 추적 대상이 아니라 개입군 배정 대상이다.", "units": [ "U-cTRAKTN" ] }, { "claim": "실제로 펨브롤리주맙을 시작한 5명에서는 지속적인 혈중 종양 신호 소실이 관찰되지 않았다. 공동 일차 평가변수는 검출률과 투여 뒤 지속적 신호 소실률이었으며, 관찰군을 닫는 계획 변경도 있었다.", "units": [ "U-cTRAKTN" ] } ], "objection": "신호가 남았다는 결과는 해당 투여군의 활성에 대한 우려를 제기하며 무시할 수 없다. 그러나 실제 투여 인원이 적고 많은 검출 환자가 이미 전이를 보였으므로, 이 결과를 모든 검사 기반 개입이나 약제의 재발·생존 효과에 대한 확정적 결론으로 확대하기는 어렵다.", "changesMind": "더 이른 검출이 영상상 재발 전 개입에 실제로 연결되는지 확인하고, 충분한 규모의 비교 연구가 재발·생존과 위해를 평가하면 검사 기반 전략을 다시 판단한다. 신호 소실이 좋아져도 환자 결과의 개선은 별도로 확인한다.", "next": [ "혈액 추적 시작, 신호 검출, 병기 검사, 개입 제안, 실제 투여를 서로 다른 단계와 분모로 정리한다", "검사 시점과 민감도가 개입 가능 인원에 미치는 자료를 찾고, 신호 소실과 재발·생존 결과를 나누어 검토한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "holdStatus": "held" }, { "id": "QP-23", "program": "colorectal", "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-NICHE2", "U-DOSTrectal", "U-KN177", "U-CM8HW" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "완전반응 뒤에도 완치는 따로 확인함", "question": "불일치 복구 결핍 대장·직장암에서 수술 전 면역치료 뒤의 완전반응이나 전이성 질환의 오래 지속되는 반응을 곧바로 완치로 기록할 수 있는가?", "judgment": "반응과 지속적 질병 제어의 근거로 인정하되 완치 확정 판단은 보류한다. 절제 조직의 병리학적 완전반응, 수술하지 않은 직장의 임상적 완전반응, 전이성 질환의 반응 지속기간과 무진행생존을 서로 다른 결과로 기록한다. 각 결과에 추적기간과 재발·사망 확인 범위를 함께 붙인다.", "basis": [ { "claim": "국소 진행 불일치 복구 결핍 결장암 연구는 니볼루맙과 이필리무맙 뒤 수술을 전제로 했으며 절제 조직의 병리학적 반응을 평가했다. 보고 시점까지 재발이 없었다는 관찰이 수술 생략의 안전성이나 영구적 완치를 입증하지는 않는다.", "units": [ "U-NICHE2" ] }, { "claim": "도스타를리맙 직장암 연구에서는 임상적 완전반응을 보인 치료 완료자들이 비수술 관리를 선택했다. 확대 보고에는 직장 이외 고형암 코호트도 포함되므로 전체 코호트의 재발·안전성 수치를 직장암만의 결과로 읽지 않는다.", "units": [ "U-DOSTrectal" ] }, { "claim": "전이성 대장암 무작위 연구는 펨브롤리주맙의 무진행생존 개선과 장기간 지속되는 반응을 보고했다. 그러나 계획된 최종 전체 생존 분석은 사전에 정한 유의수준을 충족하지 않았고, 후속 장기 추적 결과가 이 검정 이력을 바꾸지는 않는다.", "units": [ "U-KN177" ] }, { "claim": "면역치료를 받지 않은, 절제 불가능하거나 전이된 불일치 복구 결핍 또는 고빈도 현미부수체 불안정성 대장암의 체크메이트 에이트에이치더블유 연구에서는 니볼루맙·이필리무맙 병용이 첫 치료의 항암요법 비교와 모든 치료 차수의 니볼루맙 단독 비교에서 각각 무진행생존을 개선했다. 두 결과는 중앙 확인 집단을 대상으로 한 같은 시험의 사전 지정 중간 분석이며, 비교군과 분모가 달라 합산하지 않는다. 이 결과는 전체 생존 이득이나 국소 직장암의 수술 생략·완치를 입증하지 않는다.", "units": [ "U-CM8HW" ] } ], "objection": "장기간 유지되는 반응과 장기 보존은 중요한 성과이며 완치 가능성을 연구할 이유가 된다. 다만 서로 다른 병기와 평가 방법에서 얻은 성과를 하나의 완치율로 합치면 수술의 기여, 늦은 재발과 추적 누락을 가릴 수 있다.", "changesMind": "같은 대상군과 평가 기준에서 충분히 성숙한 재발·전체 생존 및 구제치료 자료가 축적되고 독립된 연구에서도 지속성이 확인되면 완치와 관련한 판단을 다시 평가한다. 반응률 상승이나 영상상 소실만으로는 이 판단을 바꾸지 않는다.", "next": [ "병리학적 반응, 임상적 반응, 반응 지속기간의 평가 방법과 분모를 구분해 기록한다", "국소 재성장, 원격 재발, 구제 수술과 장기 생존을 추적한 후속 보고를 같은 시험의 근거에 연결한다", "전이성 무작위 비교의 치료 차수, 중앙 확인 효능 집단과 실제 치료 안전성 집단을 나누고 공동 일차 평가변수의 분석 시점을 기록한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-24", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-DYNAMIC", "U-DYNAMIC3", "U-GALAXY", "U-ctDNAYang20", "U-ctDNAYuan23", "U-cTRAKTN" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "암종을 옮긴 잔존 신호의 유용성은 보류", "question": "2기 결장암에서 순환 종양 유전물질에 따라 보조치료를 정한 전략이 비열등성을 충족했다면, 그 결과를 3기 결장암이나 위암·유방암의 검사 기반 치료 이득으로 옮길 수 있는가?", "judgment": "2기 결장암의 해당 관리 전략을 뒷받침하는 근거로 인정하되, 병기와 암종을 바꾼 임상적 유용성 판단은 별도로 둔다. 3기 결장암에서 검사 음성군의 치료 축소는 재발 없는 생존의 비열등성을 충족하지 못했고, 양성군의 항암요법 강화도 개선을 입증하지 못했다. 재발 위험과의 연관성, 개입 기회, 검사에 따라 치료를 바꾼 이득을 구분하며 다른 암종으로 확대하는 판단은 보류한다.", "basis": [ { "claim": "2기 결장암의 다이내믹 시험은 검사 기반 관리와 기존 임상·병리 기준 관리를 무작위 비교했다. 검사 기반 군은 보조항암요법 사용을 줄이면서 일차 재발 없는 생존 평가에서 비열등성을 충족했다. 양성 환자만을 항암요법과 관찰로 무작위 배정한 시험은 아니다.", "units": [ "U-DYNAMIC" ] }, { "claim": "3기 결장암의 별도 무작위 연구에서 검사 음성군의 치료 축소는 옥살리플라틴 사용과 입원을 줄였으나 3년 재발 없는 생존의 비열등성을 충족하지 못했다. 양성군의 치료 강화는 2년 재발 없는 생존을 개선하지 못했다. 두 검사군의 평가 시점이 다르며, 위험 구분이 잘된다는 관찰이 치료 변경의 이득을 대신하지 않는다.", "units": [ "U-DYNAMIC3" ] }, { "claim": "근치를 목적으로 절제한 대장암의 갤럭시 관찰연구에서는 혈중 잔존 종양 신호가 더 나쁜 무질병생존과 전체 생존에 연관됐다. 항암치료 여부를 무작위로 배정한 연구가 아니므로 이 연관성을 검사에 따른 치료 변경의 이득으로 바꾸지 않는다. 앞선 보고를 확대한 같은 코호트이므로 별도의 독립 근거로 중복 계산하지 않는다.", "units": [ "U-GALAXY" ] }, { "claim": "위암의 두 전향적 코호트는 수술 후 또는 보조항암요법 후 혈중 종양 신호와 재발 위험의 연관성을 보고했다. 이는 검사에 따라 치료를 바꾸는 전략의 이득을 검증한 무작위 비교가 아니다.", "units": [ "U-ctDNAYang20", "U-ctDNAYuan23" ] }, { "claim": "삼중음성 유방암의 검사 기반 개입 연구에서는 개입군에 배정된 검출 환자 다수가 병기 검사에서 이미 전이를 보였고 실제 펨브롤리주맙 투여에 도달한 인원은 적었다. 제한된 투여 결과를 모든 검사 기반 개입의 실패로 확대하지 않는다.", "units": [ "U-cTRAKTN" ] } ], "objection": "잔존 종양에서 나온 혈액 신호라는 공통성은 병기와 암종을 넓힌 연구를 검토할 이유가 된다. 그러나 검사 시점, 기존 치료, 재발 양상과 개입 약제가 다르면 같은 전략의 이득을 보장하지 않는다. 3기에서 비열등성을 충족하지 못했다는 결과 역시 모든 검사 기반 치료 축소의 위해를 입증한 것은 아니다. 관찰 대상이 많아져도 치료 선택에 따른 교란이 사라지지는 않는다.", "changesMind": "대상 암종과 병기에서 검사 시점과 개입 규칙을 사전에 정한 비교 연구가 재발·생존과 위해를 평가하면 판단을 바꿀 수 있다. 검출률이나 위험 예측 성능만 좋아진 경우에는 환자 결과에 대한 판단을 유지한다.", "next": [ "암종·병기·표준치료·검출 시점별로 위험 예측 근거와 실제 개입 결과를 나란히 정리한다", "3기 연구의 비열등성 한계와 차이의 신뢰구간을 원문에서 확인하고, 음성군·양성군의 서로 다른 평가 시점을 유지한다" ], "by": "Codex (GPT-6)", "added": "2026-09-28", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-25", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-KoreaThyScreen16" ], "asOf": "2026-09-28", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-28", "title": "늘어난 진단과 검진의 이득은 별개", "question": "검진이 많은 지역에서 갑상선암 진단도 많고 사망률과의 연관은 보이지 않았다면, 이를 실제 질병의 증가나 개인별 검진 이득의 크기로 해석할 수 있는가?", "judgment": "진단 빈도에 검진이 기여했을 가능성을 뒷받침하는 지역 단위 근거로 기록한다. 이 자료만으로 개인별 과잉진단 여부나 검진의 이득과 위해를 확정하는 판단은 보류한다. 사망률과의 지역 상관이 관찰되지 않았다는 결과를 모든 개인에서 효과가 없다는 뜻으로 옮기지 않는다.", "basis": [ { "claim": "한국 지역사회건강조사의 검진 응답과 암등록 발생 자료, 사망 통계를 지역별로 연결해 분석했다. 검진받은 개인과 받지 않은 개인의 이후 사망을 직접 비교한 추적 연구는 아니다.", "units": [ "U-KoreaThyScreen16" ] }, { "claim": "지역별 검진 빈도는 유두암의 발견과 양의 상관을 보였지만 갑상선암 사망률과는 연관이 관찰되지 않았다. 발생과 사망을 관찰한 기간도 서로 완전히 같지 않았다.", "units": [ "U-KoreaThyScreen16" ] } ], "objection": "진단 증가와 사망률의 분리는 과잉진단을 의심할 중요한 단서이며 단순한 우연으로 버릴 이유는 없다. 다만 지역의 의료 접근성이나 다른 차이가 섞일 수 있고, 진단된 종양 가운데 평생 증상을 일으키지 않았을 종양을 이 설계로 개인별 식별할 수는 없다.", "changesMind": "대상군과 관찰기간을 맞춘 비교 자료가 검진 노출, 갑상선암 사망과 진단·치료의 위해를 함께 평가하고 지역 차이를 넘어 같은 방향을 보이면 이득과 위해에 대한 판단을 갱신한다. 발견 건수의 증가만으로는 판단을 바꾸지 않는다.", "next": [ "검진 응답, 암 발생, 사망 자료의 분석 단위와 관찰기간을 나란히 기록한다", "검진 노출과 장기 결과를 개인 수준에서 연결한 비교 연구를 찾아 지역 상관과 구분한다" ], "holdStatus": "held" }, { "id": "QP-26", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-HashimotoPTC17" ], "asOf": "2026-09-28", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-28", "title": "갑상선염과 암의 동반에서 인과를 보류", "question": "하시모토 갑상선염 환자에서 유두암이 더 자주 확인됐다는 통합 결과를 갑상선염이 암을 일으킨다는 근거로 받아들일 수 있는가?", "judgment": "함께 관찰되는 연관성의 근거로 남기되 인과 판단은 보류한다. 수술 조직, 세침흡인 검사 대상, 선택적으로 검사를 받은 표본을 나누어 읽는다. 세침흡인 연구라는 이름만으로 일반 인구를 대표하는 코호트라고 분류하지 않으며, 수술 표본의 동반 빈도를 일반 인구의 새 암 발생 위험으로 바꾸지 않는다.", "basis": [ { "claim": "이 메타분석은 갑상선 절제 조직 연구와 세침흡인 연구, 선택적 세침흡인 또는 절제 연구를 합쳤다. 갑상선염이 있는 집단과 없는 집단을 비교한 전체 통합 오즈비는 유두암과의 양의 연관성을 보였다.", "units": [ "U-HashimotoPTC17" ] }, { "claim": "갑상선염 환자 중 유두암이 확인되는 비율은 표본 확보 방식에 따라 크게 달랐다. 수술로 얻은 조직과 검사 대상으로 선택된 환자는 일반 인구에서 출발해 새 발생을 추적한 집단과 같은 분모가 아니다.", "units": [ "U-HashimotoPTC17" ] } ], "objection": "반복되는 연관성은 염증과 종양 사이의 생물학적 연결을 연구할 이유가 된다. 그러나 수술을 받게 된 이유, 검사 강도, 갑상선염과 암의 판정 방법이 다르면 발견 기회 자체가 달라지므로 통합 연관성만으로 인과 방향을 정할 수 없다.", "changesMind": "일반 인구에서 출발한 전향적 자료가 갑상선염의 선행 여부를 확인하고 검사 빈도와 관련 요인을 고려한 뒤에도 새 유두암 발생의 차이를 일관되게 보이면 인과 가설의 근거를 강화한다. 그래도 관찰 연관성만으로 확정된 원인이라고 기록하지 않는다.", "next": [ "각 원연구의 모집 경로, 수술·검사 선택 기준과 갑상선염 판정 방법을 구분한다", "수술 표본과 일반 인구 코호트를 분리하고 검사 빈도를 고려한 결과가 있는지 확인한다" ], "holdStatus": "held" }, { "id": "QP-27", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-SELECT", "U-T-DECISION", "U-T-COSMIC311", "U-T-LIBRETTO531", "U-T-LIBRETTO001", "U-T-ROAR" ], "asOf": "2026-09-28", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-28", "title": "반응률은 비교 시험의 결론을 대신 못함", "question": "단일군 갑상선암 연구에서 관찰한 높은 종양 반응을 무작위 비교에서 확인한 무진행생존 개선과 같은 근거로 볼 수 있는가?", "judgment": "단일군 반응은 해당 선별 집단에서 관찰된 항종양 활성으로 인정하되 다른 치료보다 우월하다는 판단은 보류한다. 무작위 비교의 무진행생존, 단일군 반응, 전체 생존과 완치를 별도로 기록한다. RET 변이 수질암, RET 융합 갑상선암, BRAF V600E 변이 역형성암과 방사성요오드 불응성 분화암의 결과를 한 집단의 성적으로 합치지 않는다.", "basis": [ { "claim": "방사성요오드 불응성 분화암에서 렌바티닙과 소라페닙은 각각 위약과 비교한 무작위 시험에서 무진행생존 개선을 보고했다. 서로 다른 시험의 효과 크기를 직접 약제 순위로 바꾸지는 않는다.", "units": [ "U-T-SELECT", "U-T-DECISION" ] }, { "claim": "이전에 혈관성장인자 수용체 표적치료를 받은 분화암의 카보잔티닙 시험은 무진행생존 중간 분석에서 사전 기준을 충족했지만 일차 객관적 반응률 검정은 사전 유의수준에 도달하지 못했다. 두 평가변수의 분석 대상도 달랐다.", "units": [ "U-T-COSMIC311" ] }, { "claim": "셀퍼카티닙 단일군 연구는 이전 치료 여부가 다른 RET 변이 수질암과 이전 치료를 받은 RET 융합 갑상선암을 나누어 보고했다. 후속 무작위 시험의 기존 약제 대비 무진행생존 개선은 RET 변이 수질암에서 얻은 결과이며 융합 집단의 비교 효과까지 입증한 것은 아니다.", "units": [ "U-T-LIBRETTO001", "U-T-LIBRETTO531" ] }, { "claim": "다브라페닙과 트라메티닙 병용 바스켓 연구의 해당 보고는 BRAF V600E 변이를 가진 절제 불가능 또는 전이성 역형성암 집단의 단일군 결과다. 관찰된 반응과 생존기간은 무작위 대조군과 비교한 생존 개선이나 분화암의 재분화 효과를 입증하지 않는다.", "units": [ "U-T-ROAR" ] } ], "objection": "드문 분자 집단이나 공격적인 암에서는 뚜렷하고 지속적인 단일군 반응도 연구상 중요한 근거다. 그러나 반응의 크기가 커도 환자 선택과 이전 치료의 차이가 사라지지 않으며, 진행을 늦춘 결과만으로 전체 생존 이득이나 완치를 대신할 수는 없다.", "changesMind": "같은 조직형, 분자 선별 기준과 치료 이력에서 적절한 비교 연구가 사전에 정한 평가변수와 위해를 함께 검증하면 상대 효과 판단을 갱신한다. 새 단일군 보고가 추가된 경우에는 활성의 재현성을 보강하되 비교 효과의 근거 등급을 자동으로 올리지 않는다.", "next": [ "각 시험의 조직형, 변이와 융합, 이전 치료, 대조군 및 평가변수별 판정 상태를 나누어 기록한다", "반응의 지속성과 후속 생존·위해 보고를 같은 시험에 연결하되 단일군과 무작위 근거를 구분한다" ], "holdStatus": "held" }, { "id": "QP-28", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-HER2Residual26", "U-KATHERINE" ], "asOf": "2026-09-30", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-29", "title": "잔존암의 표적 변화는 약효 증거와 별개", "question": "선행치료 뒤 잔존 침윤암에서 HER2 과발현이 사라졌다는 관찰만으로 이후 표적치료의 이득까지 달라진다고 판단할 수 있는가?", "judgment": "잔존 검체의 HER2 분류 변화만으로 후속 표적치료의 이득이 사라진다고 판단하지 않는다. 기존 보류 판단에 KATHERINE의 치료 후 음성 하위군과 장기 추적을 반영한다. 해당 비교는 트라스투주맙 엠탄신의 이득과 일치하는 방향이지만, 작은 탐색 하위군이므로 효과 크기의 확정이나 재검사에 따른 치료 선택 전략의 유용성 판단은 보류한다.", "basis": [ { "claim": "단일기관 후향 연구는 선행 표적치료를 받은 전체 환자 중 재평가에 충분한 잔존 침윤암이 있는 일부에서 HER2를 판정했다. 보고된 변화 빈도의 분모는 재평가 가능한 잔존암 집단이며 전체 치료 환자가 아니다.", "units": [ "U-HER2Residual26" ] }, { "claim": "이 관찰연구 초록은 면역조직화학과 유전자 증폭 검사에 따른 상태 변화를 보고하지만 보조치료 변경의 재발·생존 이득을 비교하지 않았다.", "units": [ "U-HER2Residual26" ] }, { "claim": "KATHERINE의 짝지은 검체 하위군은 치료 전 양성이면서 잔존암 재검사에서 음성이었던 환자를 따로 보고했다. 후속 장기 추적에서도 트라스투주맙 엠탄신군의 침윤성 무질병생존 추정치가 트라스투주맙군보다 높았다. 두 보고는 같은 시험·같은 하위군의 추적이며 독립 근거로 더 세지 않는다.", "units": [ "U-KATHERINE" ] } ], "objection": "원래 시험은 무작위 비교지만 잔존암의 재검사 상태는 배정 때 알려져 있지 않았고 이 하위군의 군별 크기도 다르다. 검체 누락과 판정 불확실성이 있으며 일부 음성 분류에는 유전자 증폭 검사 결과를 알 수 없는 검체가 포함됐다. 관찰된 방향을 모든 잔존암이나 다른 접합체에 일반화하지 않는다.", "changesMind": "더 큰 별도 환자군에서 같은 판정 기준으로 얻은 비교 결과와 불확실성, 또는 재검사 기반 선택 전략의 임상 결과가 확보되면 판단을 갱신한다. 다른 접합체의 전체 시험 결과만으로 이 하위군의 이득을 대신하지 않는다.", "next": [ "검체 확보 여부와 재검사 기준을 맞춰 별도 환자군의 결과를 찾는다", "기존 하위군의 효과와 표적 상태에 따른 효과 차이 검정을 구분하고, 재검사 기반 치료 선택 전략은 별도 질문으로 남긴다" ], "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-29", "program": "gxb", "targets": [ "TACSTD2", "ERBB2", "CD274", "PARP1", "PDCD1" ], "biomarkers": [ "BM-gBRCA" ], "units": [ "U-TROPIONB01", "U-EGF100151", "U-JAVG100", "U-EMBRACA", "U-AVAGAST", "U-ATTR4" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "진행 억제와 생존 개선을 따로 판정", "question": "종양의 진행을 늦춘 결과와 전체 생존 검정이 일치하지 않을 때, 연구 전체를 성공이나 실패 한 가지로만 기록할 수 있는가?", "judgment": "평가변수별로 판정한다. 무진행생존이나 진행까지의 시간에서 확인된 개선은 남기되 전체 생존 이득까지 입증했다고 쓰지 않는다. 전체 생존의 통계적 유의성이 없다는 결과도 두 치료가 동등하거나 이득이 전혀 없다는 증명으로 바꾸지 않는다. 후속 치료나 교차 투여의 영향을 근거로 미확인 생존 이득을 확정하는 판단은 보류한다.", "basis": [ { "claim": "이전에 치료받은 호르몬 수용체 양성·허투 음성 진행성 유방암에서 다토포타맙 데룩스테칸은 의사 선택 항암요법보다 무진행생존을 개선했지만, 최종 전체 생존 분석은 통계적 유의성에 도달하지 못했다. 두 지표는 공동 일차 평가변수였다.", "units": [ "U-TROPIONB01" ] }, { "claim": "이전 치료 뒤 진행한 허투 양성 유방암에서 라파티닙과 카페시타빈 병용은 카페시타빈 단독보다 진행까지의 시간을 늘렸다. 최종 전체 생존의 군 간 차이는 통계적으로 유의하지 않았으며, 조기 등록 종료와 이후 교차 투여를 고려한 탐색적 보정 분석은 주분석과 구분해야 한다.", "units": [ "U-EGF100151" ] }, { "claim": "진행성 위암·위식도접합부암의 유도 항암요법 뒤 진행하지 않은 환자에서 아벨루맙 유지요법은 항암요법 지속보다 전체 생존의 우월성을 입증하지 못했다. 전체 무작위 집단과 사전 지정한 피디엘원 양성 집단의 일차 결과를 다른 검사 기준을 쓴 탐색적 하위군으로 대신하지 않는다.", "units": [ "U-JAVG100" ] }, { "claim": "생식세포 브라카 변이가 있는 허투 음성 진행성 유방암의 엠브라카 연구에서는 탈라조파립이 의사 선택 항암요법보다 무진행생존을 개선했지만, 최종 전체 생존의 유의한 개선은 확인되지 않았다. 환자 보고 삶의 질과 유방 증상의 유리한 결과는 별도로 기록하며, 이후 백금계나 다른 파프 억제제의 사용을 미확인 생존 이득의 증명으로 삼지 않는다.", "units": [ "U-EMBRACA" ] }, { "claim": "진행성 위암·위식도접합부 선암의 일차 치료에서 같은 항암요법에 베바시주맙을 더한 군과 위약을 더한 군을 비교한 이중맹검 위약 대조 삼상 연구에서는 일차 평가변수인 전체 생존의 유의한 개선이 확인되지 않았다. 무진행생존과 반응률의 개선은 일차 판정을 뒤집지 않으며, 유의하지 않음이 동등함이나 효과 부재의 증명이 되지도 않는다.", "units": [ "U-AVAGAST" ] }, { "claim": "허투 음성 미치료 절제불가 진행·재발 위암·위식도접합부암의 일차 치료에서 같은 항암요법에 니볼루맙을 더한 군과 위약을 더한 군을 비교한 이중맹검 위약 대조 연구에서는 중앙 판정에 따른 무진행생존의 개선이 확인됐지만 전체 생존의 유의한 개선은 확인되지 않았고 긴 추적에서도 같은 갈림이 유지됐다. 유의하지 않은 전체 생존이 효과 부재의 증명이 되지는 않으며 생존자 조건부 사후 관찰을 전체 생존 이득의 증명으로 삼지 않는다.", "units": [ "U-ATTR4" ] } ], "objection": "진행 억제 효과는 전체 생존과 별도로 기록하고, 유의하지 않은 전체 생존을 동등함이나 효과 부재의 증명으로 바꾸지 않는다. 이차변수 개선이나 사후 관찰로 일차 전체 생존 판정을 대신하지 않는다.", "changesMind": "사전에 정한 전체 생존 기준을 충족하는 후속 결과나 정정이 공개되면 갱신한다. 보정 분석은 보조 근거로만 다루고 탐색적 하위군이나 생존자 조건부 관찰만으로 일차 판정을 뒤집지 않는다.", "next": [ "각 시험의 일차·공동 일차 평가변수와 최종·중간 분석, 검정 기준을 원논문에 맞춰 나누어 기록한다", "후속 약제의 불균형과 교차 투여를 구분하고 보정 분석이 필요로 하는 가정과 불확실성을 확인한다", "생식세포 변이로 선별된 연구의 무작위 배정 인원과 실제 치료 안전성 분모를 구분하고, 효능과 환자 보고 결과를 다른 평가변수로 연결한다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Muse Spark1.3", "holdStatus": "held" }, { "id": "QP-30", "program": "gxb", "targets": [ "PDCD1", "CDK4/6" ], "biomarkers": [], "units": [ "U-KN522", "U-monarchE", "U-CLASSIC", "U-KN585" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "장기 추적에 맞춰 생존 판단을 고침", "question": "병리학적 완전반응이나 재발 관련 평가변수의 개선으로 먼저 알려진 연구에서 장기 전체 생존 결과가 공개되면 기존 판단을 어떻게 고칠 것인가?", "judgment": "전체 생존을 직접 평가한 후속 근거에 맞춰 판단을 갱신한다. 초기 반응이나 무질병생존으로 생존 이득을 미리 추정하지 않고, 반대로 유의한 후속 결과가 나왔는데도 생존 미확인이라는 옛 상태를 유지하지 않는다. 같은 시험의 추적 보고는 기존 근거 단위에 연결하며 독립 시험으로 세지 않는다. 확인된 생존 이득을 완치나 다른 병기·위험 집단의 효과로 확대하는 판단은 보류한다.", "basis": [ { "claim": "치료받지 않은 초기 삼중음성 유방암에서 펨브롤리주맙을 수술 전 항암요법과 병용하고 수술 후에도 이어 간 전략은 병리학적 완전반응과 무사건생존 개선에 이어 최종 전체 생존 분석에서도 유의한 개선을 보고했다. 전체 생존은 이차 평가변수였다.", "units": [ "U-KN522" ] }, { "claim": "림프절 양성인 고위험 호르몬 수용체 양성·허투 음성 초기 유방암에서 아베마시클립과 내분비요법 병용은 침윤성 무질병생존을 개선했다. 앞선 중간 분석의 전체 생존 차이는 유의하지 않았으나, 후속 주요 전체 생존 분석은 사전 유의성 기준을 충족했다.", "units": [ "U-monarchE" ] }, { "claim": "림프절 곽청을 포함한 근치 위절제술을 받은 2·3기 위암에서 카페시타빈과 옥살리플라틴 보조요법은 관찰군보다 무질병생존을 개선했고, 사전 계획된 장기 추적에서도 전체 생존 개선을 보고했다. 후속 보고에서는 일차 분석 이후의 이상반응 자료를 새로 수집하지 않았다고 밝혔다.", "units": [ "U-CLASSIC" ] }, { "claim": "위암의 펨브롤리주맙 수술 전후 연구는 병리학적 완전반응이 개선됐으나 무사건생존의 사전 유의수준을 충족하지 못했다. 최종 전체 생존 보고에서도 이득을 확정하지 못했으므로 초기 반응의 개선을 생존 성공으로 바꾸지 않는다.", "units": [ "U-KN585" ] } ], "objection": "추적기간이 길어졌다고 모든 결과의 신뢰도가 자동으로 높아지지는 않는다. 반복 검정의 기준, 남은 추적 대상, 후속 치료와 위해 자료의 관찰기간을 확인해야 하며, 한 시험에서 지표들이 같은 방향을 보였다고 다른 연구의 초기 지표까지 생존의 대리 지표로 인정할 수는 없다.", "changesMind": "사전 분석계획과 맞는 추가 추적이나 정정이 효과의 방향·크기·불확실성을 바꾸면 해당 시험의 판단을 갱신한다. 초기 반응을 다른 연구의 장기 생존 대신 쓰려면 그 대리 관계를 별도로 검증한 근거가 필요하다.", "next": [ "각 시험의 최초 결과와 후속 전체 생존 보고를 한 단위 안에서 발표 시점·자료 마감일·평가변수별로 연결한다", "장기 효능과 위해의 관찰기간이 같은지 확인하고 더는 수집하지 않은 안전성 자료를 장기 안전성 확인으로 쓰지 않는다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-31", "program": "gxb", "targets": [ "CD274", "PDCD1" ], "biomarkers": [], "units": [ "U-MATTERHORN", "U-KN522", "U-KN585", "U-ATT5", "U-CRITICS", "U-DRAGONIV" ], "asOf": "2026-10-01", "status": "판단 기록됨", "title": "수술 전후 병용의 기여는 분리 못함", "question": "수술 전과 후에 면역치료를 함께 배정한 전략이 생존을 개선했다면, 어느 단계의 투여가 이득을 만들었는지 따로 결론 낼 수 있는가?", "judgment": "무작위 배정된 전체 치료 전략의 비교 효과로 기록한다. 수술 전 병용, 수술 후 병용과 이어지는 단독 투여가 함께 달라졌다면 어느 단계가 필요하거나 생략 가능한지에 대한 판단은 보류한다. 병리학적 반응이나 실제 투여 완료 여부로 나눈 결과만으로 각 단계의 인과적 기여를 분리하지 않는다. 추가된 연구의 수술 시점 병리반응은 수술 전 투여에 대한 결과이며 수술 후 투여의 효과가 아니다. 두 약제를 함께 더한 비교만으로 각 약제의 기여를 분리하거나, 병리반응 개선만으로 전체 수술 전후 전략의 재발·생존 이득을 확정하지 않는다.", "basis": [ { "claim": "절제 가능한 위암·위식도접합부암 연구는 도세탁셀 기반 수술 전후 항암요법에 더발루맙 또는 위약을 함께 투여하고 이후에도 더발루맙 또는 위약을 이어 가는 전략을 비교했다. 무사건생존 개선에 이어 최신 최종 전체 생존 보고도 해당 검정의 유의성 기준을 충족했다.", "units": [ "U-MATTERHORN" ] }, { "claim": "초기 삼중음성 유방암 연구에서도 수술 전 펨브롤리주맙과 항암요법의 병용 및 수술 후 펨브롤리주맙을 한 배정군의 전략으로 비교했다. 무사건생존과 전체 생존 결과는 수술 후 약제만 별도로 무작위 비교한 결과가 아니다.", "units": [ "U-KN522" ] }, { "claim": "두 시험에서 수술 후 투여는 최초 배정 전략에 포함됐다. 현재 연결한 시험들은 수술 전 투여를 동일하게 고정한 뒤 수술 후 면역치료 유무만 따로 무작위 배정하는 설계가 아니다.", "units": [ "U-MATTERHORN", "U-KN522" ] }, { "claim": "위암에서 펨브롤리주맙을 수술 전후 항암요법에 더한 연구와 니볼루맙을 수술 후 항암요법에 더한 연구는 각각 무사건생존의 사전 유의수준 또는 무재발생존의 개선을 입증하지 못했다. 항암요법의 구성·수술 시점·선별 조건이 다른 연구의 결과만으로 어느 치료 단계가 효과를 결정했는지 분리할 수 없다.", "units": [ "U-KN585", "U-ATT5" ] }, { "claim": "위암의 별도 항암요법 연구는 수술 전 치료를 시작하기 전에 전체 전략을 배정한 뒤, 수술 후 항암요법과 항암방사선요법을 비교했다. 전체 배정군 분석에서 전체 생존 개선이 확인되지 않았고 수술 후 치료를 시작하지 못한 환자도 포함됐다. 이는 면역치료 연구가 아니며, 실제 수술 후 투여자만 골라 읽으면 최초 배정의 비교 가능성이 달라진다는 설계상의 참고 근거다.", "units": [ "U-CRITICS" ] }, { "claim": "추가된 위암 수술 전후 병용 연구는 항암요법에 캄렐리주맙과 저용량 리보세라닙을 함께 더한 전략을 항암요법 단독과 비교했다. 이번 초록은 병리학적 완전반응을 보고하고 공동 일차 평가변수인 무사건생존 결과는 제시하지 않는다. 수술 시점의 반응은 수술 후 투여의 결과가 아니며, 두 약제의 개별 기여나 전체 전략의 생존 이득을 이 반응 결과만으로 확정할 수 없다.", "units": [ "U-DRAGONIV" ] } ], "objection": "병리학적 반응과 투여 완료 양상은 어느 단계의 기여가 클지 가설을 세우는 단서가 된다. 다만 수술에 도달하거나 후속 치료를 마칠 수 있었는지는 치료 이후의 상태이므로, 그런 집단끼리의 차이를 별도 무작위 비교처럼 읽으면 선택의 영향을 약효로 잘못 돌릴 수 있다.", "changesMind": "수술 전 치료가 같은 환자들을 수술 후 치료 유무로 무작위 비교하거나, 각 단계의 기여를 구분하도록 미리 설계한 비교 근거가 확보되면 단계별 판단을 갱신한다. 투여를 마친 환자의 결과가 좋다는 관찰만으로 특정 단계를 생략할 수 있다고 결론 내리지 않는다.", "next": [ "배정 시점, 수술 전후 약제 구성과 후속 단독 투여를 시험별 시간표로 정리한다", "수술 미도달과 수술 후 투여 미시작·중단을 최초 배정 분모와 구분하고, 실제 투여자 분석을 별도 무작위 비교로 읽지 않는다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; source-checked and integrated by Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-32", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-DB05", "U-KATHERINE" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "잔존암 약효와 폐 위해를 함께 읽음", "question": "선행치료 뒤 남은 고위험 허투 양성 유방암에서 새로운 항체약물접합체가 침윤성 무질병생존을 개선했다면, 어느 환자 범위와 위해까지 함께 기록해야 하는가?", "judgment": "시험이 선별한 고위험 잔존 침윤암 집단에서 트라스투주맙 엠탄신 대비 트라스투주맙 데룩스테칸의 침윤성 무질병생존 개선을 인정한다. 약물 관련 간질성 폐질환의 증가와 사망 사례를 같은 판단에 포함한다. 이 결과만으로 전체 생존 이득이나 모든 잔존암 집단에서의 동일한 이득을 확정하는 판단은 보류한다.", "basis": [ { "claim": "새 무작위 비교는 선행치료 후 잔존 침윤암이 있고 수술 때 림프절 양성이거나 진단 당시 수술 불가능했던 허투 양성 유방암을 대상으로 했다. 트라스투주맙 데룩스테칸은 트라스투주맙 엠탄신보다 일차 평가변수인 침윤성 무질병생존을 개선했다.", "units": [ "U-DB05" ] }, { "claim": "같은 보고에서 판정된 약물 관련 간질성 폐질환은 트라스투주맙 데룩스테칸군에서 더 자주 발생했고 해당 군에서 간질성 폐질환 환자의 사망도 보고됐다. 저장 초록은 전체 생존을 평가 항목으로 명시하지만 그 비교 결과를 제시하지 않는다.", "units": [ "U-DB05" ] }, { "claim": "기존 잔존 침윤암 시험은 트라스투주맙 엠탄신과 트라스투주맙을 비교해 침윤성 무질병생존과 후속 전체 생존의 개선을 보고했다. 대조약과 선별 범위가 다른 이 결과를 새 두 접합체의 직접 비교 결과나 모든 잔존암의 성적으로 대신할 수는 없다.", "units": [ "U-KATHERINE" ] } ], "objection": "새 시험의 재발 관련 개선은 후속 연구 판단을 갱신할 중요한 근거이며 위해가 있다고 그 효과가 사라지는 것은 아니다. 동시에 이상반응의 전체 빈도나 무질병생존 한 지표만으로 서로 다른 위해의 중증도·지속성·사망을 하나의 순이득 점수로 합칠 수는 없다.", "changesMind": "같은 시험의 성숙한 전체 생존과 장기 안전성 결과가 공개되면 이득과 위해의 판단을 함께 갱신한다. 등록 조건 밖의 잔존암으로 범위를 넓히려면 그 집단을 포함한 비교 근거가 필요하며, 두 시험의 수치를 단순 비교한 결과만으로 확대하지 않는다.", "next": [ "잔존암 여부와 별도로 진단 당시 수술 가능성, 수술 때 림프절 상태 및 대조약을 기록한다", "간질성 폐질환의 판정·중증도·사망과 치료 중단을 효능 결과 옆에 두고 후속 생존 및 정정 보고를 확인한다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "holdStatus": "held" }, { "id": "QP-33", "program": "breast", "targets": [ "TACSTD2", "PDCD1" ], "biomarkers": [], "units": [ "U-ASCENT04", "U-ASCENT", "U-ASCENT03" ], "asOf": "2026-10-01", "status": "판단 기록됨", "title": "선별된 진행성 병용 결과의 적용 범위", "question": "피디엘원 양성으로 선별한 진행성 삼중음성 유방암의 첫 치료에서 병용요법이 무진행생존을 늘렸다면, 그 결론을 전체 삼중음성 유방암이나 약제 단독 효과로 옮길 수 있는가?", "judgment": "옮기지 않는다. 절제 불가능한 국소 진행성 또는 전이성 질환에서 해당 선별 기준을 충족한 환자의 첫 치료 비교로 기록한다. 두 군 모두 펨브롤리주맙을 사용했으므로 사시투주맙 고비테칸 단독의 효과나 펨브롤리주맙을 추가한 이득을 이 시험으로 따로 정하지 않는다. 전체 생존 자료가 미성숙하므로 생존 개선과 다른 선별 집단으로의 확대 판단은 보류한다. ASCENT03은 PD-1 또는 PD-L1 억제제 대상이 아닌 이전 미치료 진행성 병기에서의 사시투주맙 고비테칸 대 항암요법 비교라는 별도 근거로만 추가한다. 이를 ASCENT04 병용 효과의 구성 요소 분리 증거나 모든 PD-L1 음성 집단에 대한 증명으로 사용하지 않는다.", "basis": [ { "claim": "피디엘원 양성이며 진행성 질환의 첫 치료 대상인 삼중음성 유방암의 무작위 시험에서 사시투주맙 고비테칸과 펨브롤리주맙 병용은 항암요법과 펨브롤리주맙 병용보다 독립 중앙 평가 무진행생존을 개선했다. 저장 초록에서 전체 생존 자료는 미성숙으로 보고됐다.", "units": [ "U-ASCENT04" ] }, { "claim": "같은 보고에서 두 군 모두 중증 이상반응과 사망으로 이어진 이상반응이 보고됐다. 전체 중증 이상반응 빈도와 이상반응에 따른 치료 중단은 서로 다른 결과로 제시됐다.", "units": [ "U-ASCENT04" ] }, { "claim": "기존 사시투주맙 고비테칸 시험은 재발 또는 불응성 전이성 삼중음성 유방암에서 항암요법과 비교한 단독 약제 연구였다. 이 결과를 새 시험의 첫 치료 병용 및 피디엘원 선별 조건과 같은 맥락으로 합치지 않는다.", "units": [ "U-ASCENT" ] }, { "claim": "이전 미치료 진행성 삼중음성 유방암 중 PD-1 또는 PD-L1 억제제 대상이 아닌 환자 558명을 1:1로 사시투주맙 고비테칸 대 항암요법(파클리탁셀, 알부민 결합 파클리탁셀, 또는 젬시타빈 플러스 카보플라틴)으로 비교한 개방표지 무작위 시험에서 독립 중앙 평가 무진행생존 중앙값은 9.7개월 대 6.9개월(층화 위험비 0.62, 95% CI 0.50-0.77; P<0.001)이었다. 전체 생존은 이차 평가변수였으나 초록에 수치가 보고되지 않아 생존 추론을 하지 않는다. 3등급 이상 이상반응은 66% 대 62%로 보고됐으며 치료 관련으로 한정하지 않았고 군별 안전성 분모는 초록에 없었으며, 이상반응으로 인한 투여 중단은 사시투주맙 고비테칸 4%, 적어도 하나의 항암화학요법 약제 12%였다. 일차 보고 분모 558명을 유지하고 현 등록 623명과의 차이는 해소되지 않은 차이로 두며, 논문 전문을 검토한 것으로 간주하지 않는다. 면역치료 비대상을 PD-L1 음성과 동일시하지 않는다.", "units": [ "U-ASCENT03" ] } ], "objection": "앞선 단독 약제 결과와 새 병용 비교가 같은 방향이면 연구의 연속성을 뒷받침한다. 그러나 치료 차수, 선별 기준과 병용 구성이 함께 달라졌으므로 단독 효과와 면역치료의 상호작용을 분리하거나 초기암·음성 집단의 효과까지 추정하는 근거는 되지 않는다. ASCENT03이 면역치료 비대상 집단에서 무진행생존 개선을 보여도 면역치료 비대상은 PD-L1 음성과 동일하지 않으므로, ASCENT04 병용의 각 약제 기여 분리나 모든 PD-L1 음성 하위군의 효과 확정 근거는 되지 않는다.", "changesMind": "사전 계획에 따른 성숙한 전체 생존 결과가 나오면 해당 선별 집단의 판단을 갱신한다. 다른 피디엘원 상태나 초기암에 대한 비교 자료, 각 약제의 추가 기여를 분리한 연구가 확보되면 그 질문을 별도로 다시 평가한다. ASCENT03의 사전 계획된 전체 생존 수치가 보고되면 해당 비대상 집단 판단을 별도로 갱신한다.", "next": [ "원출처의 피디엘원 검사·선별 조건과 이전 치료 허용 범위를 확인하고 다른 시험의 양성 기준을 대신 붙이지 않는다", "후속 전체 생존, 약제별 투여 중단과 위해 결과를 추적하되 병용 비교와 단독 효과 질문을 구분한다", "ASCENT03의 전체 생존 수치, 일차 보고 558명과 현 등록 623명 간 해소되지 않은 차이, 이상반응과 치료 관련 이상반응 및 무작위·치료 분모 구분을 유지하고 ASCENT04 병용과 합치지 않는다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "revisedBy": "Muse Spark1.3; revised and reviewed by Gemini Flash3.8; source-checked by Codex (GPT-6)", "revisionNote": "ASCENT-03의 별도 환자군·단독 약제 비교를 연결하되 기존 병용효과 해석과 보류 범위를 유지함.", "holdStatus": "held" }, { "id": "QP-34", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-HER2CLIMB05", "U-KATHERINE" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "유지치료의 진행 지연을 재발 예방과 구분", "question": "전이성 유방암에서 도입치료 후 진행하지 않은 환자의 유지치료 결과를 수술 후 재발 예방이나 전체 생존의 개선으로 옮길 수 있는가?", "judgment": "전이성 질환의 유지치료에서 투카티닙을 추가한 비교로 한정한다. 무진행생존 개선은 기록하되 전체 생존은 미성숙하므로 생존 개선 판단은 보류한다. 수술 후 잔존암의 보조치료와는 질환 상태·선별 시점·평가변수가 다르며 두 시험의 수치로 약제 우열을 매기지 않는다.", "basis": [ { "claim": "유지치료 시험은 도입치료 뒤 진행이 없고 뇌전이가 없거나 무증상인 환자를 선별했다. 두 군 모두 트라스투주맙과 퍼투주맙을 받았으며 투카티닙 추가군에서 연구자 평가 무진행생존이 개선됐다.", "units": [ "U-HER2CLIMB05" ] }, { "claim": "같은 초록은 전체 생존 자료가 미성숙하다고 밝혔다. 투카티닙군의 중증 설사·간효소 상승과 이상반응에 따른 투카티닙 중단을 함께 보고했으며, 이 군의 빈도를 대조군 대비 위해 증가분으로 읽지 않는다.", "units": [ "U-HER2CLIMB05" ] }, { "claim": "KATHERINE은 선행치료 후 수술에서 잔존 침윤암이 확인된 초기 질환의 보조치료 비교다. 전이성 유지치료의 진행 지연과 동일한 질문이나 환자 집단이 아니다.", "units": [ "U-KATHERINE" ] } ], "objection": "같은 HER2 표적의 치료 연속성을 연구할 근거는 된다. 그러나 도입치료 동안 진행한 환자는 유지치료 무작위 배정에 포함되지 않았으므로 처음 진단된 전체 전이성 환자에게 같은 결과가 난다고 추정할 수 없다.", "changesMind": "같은 시험의 성숙한 전체 생존과 중추신경계 결과·비교 안전성이 공개되면 판단을 갱신한다. 도입치료를 포함한 전체 전략이나 수술 후 재발 예방으로 범위를 넓히려면 해당 질문의 직접 비교가 필요하다.", "next": [ "도입치료 시작 집단과 유지치료 배정 집단을 구분하고 무작위 배정부터 계산한 추적 시점을 확인한다", "후속 생존·중추신경계·위해 결과를 같은 시험 단위에 붙이고 최초 레지스트리 게시일을 새 논문 발표일로 쓰지 않는다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "holdStatus": "held" }, { "id": "QP-35", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "units": [ "U-postMONARCH", "U-MAINTAIN", "U-PACE", "U-PALMIRA" ], "asOf": "2026-11-13", "status": "판단 기록됨", "title": "진행 뒤 약제 유지와 교체는 별개다", "question": "호르몬수용체 양성·허투 음성 진행성 유방암에서 내분비요법과 시디케이 4·6 억제제 치료 뒤 진행한 경우, 같은 계열 약제의 유지와 교체를 하나의 전략으로 판단할 수 있는가?", "judgment": "이전 약제와 바꾼 내분비요법, 새로 배정한 억제제별로 판단한다. 아베마시클립과 리보시클립을 평가한 연구의 무진행생존 개선과 팔보시클립 유지·재투여 연구의 개선 미입증을 함께 기록한다. 각 시험 안의 비교 결과를 인정하되 시험 사이의 약제 우열, 계열 전체의 지속 효과, 전체 생존 이득에 대한 판단은 보류한다. 진행 전에 변이 검출을 계기로 치료를 바꾸는 질문과도 구분한다.", "basis": [ { "claim": "이전 계열 치료 뒤 진행하거나 보조치료 중 또는 이후 재발한 환자의 제3상 연구에서는 풀베스트란트에 아베마시클립을 더한 군이 위약을 더한 군보다 연구자 평가 무진행생존에서 나은 결과를 보였다. 독립 중앙 평가도 같은 방향이었다. 같은 시험의 최종 전체 생존 분석은 사전에 정한 유의성 기준을 넘지 못했다.", "units": [ "U-postMONARCH" ] }, { "claim": "대부분 팔보시클립을 이전에 사용한 환자의 이중눈가림 제2상 연구에서는 내분비요법을 바꾸고 리보시클립 또는 위약을 더했으며 무진행생존 개선을 보고했다. 이전 약제 구성이 한쪽에 치우쳐 있어 어떤 계열 약제를 쓰다가 진행한 경우에도 같은 효과가 난다고 확대하지 않는다.", "units": [ "U-MAINTAIN" ] }, { "claim": "풀베스트란트에 팔보시클립을 더한 시험과 다른 내분비요법에 팔보시클립을 재투여한 시험은 각각의 일차 무진행생존 비교에서 유의한 개선을 입증하지 못했다. 재투여 시험에서는 치료 중 발생한 중증 이상반응이 더 많았다. 개선 미입증은 동등성이나 모든 하위군의 효과 부재를 입증한 것은 아니다.", "units": [ "U-PACE", "U-PALMIRA" ] }, { "claim": "아벨루맙을 포함한 삼제 병용군의 탐색 결과는 면역치료의 추가 이득을 확정하지 못했다. 변이별 탐색 관찰만으로 특정 바이오마커가 약효를 예측한다고 결론 내리지 않는다.", "units": [ "U-PACE" ] } ], "objection": "같은 계열의 다른 약제로 바꾼 연구와 팔보시클립을 이어 쓴 연구의 결과 차이는 후속 가설의 단서가 된다. 그러나 환자 선별, 이전 치료, 내분비요법과 대조군이 달라 그 차이를 약제 교체 자체의 효과나 약제 간 순위로 확정할 수 없다.", "changesMind": "이전 약제와 진행 시점이 같은 집단에서 유지·교체 전략을 직접 비교하거나, 사전에 정한 하위군과 상호작용이 독립적으로 확인되면 해당 범위의 판단을 갱신한다. 성숙한 전체 생존과 비교 안전성 자료는 무진행생존 결과와 별도로 평가한다.", "next": [ "시험별 이전 억제제, 내분비요법 교체, 진행·재발 조건과 평가자를 나란히 기록한다", "중앙 평가를 별도 시험으로 세지 않고 후속 생존·위해·사전 하위군 결과를 같은 근거 단위에 연결한다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-11-13", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-36", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-ExteNET", "U-KAITLIN", "U-KATHERINE", "U-APT", "U-TRAIN2" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "표적이 같아도 수술 뒤 조건은 다르다", "question": "허투 양성 조기 유방암의 수술 후 표적치료 연구에서 결과가 갈릴 때, 약제 이름보다 먼저 어떤 모집 조건과 비교 질문을 확인해야 하는가?", "judgment": "수술 후 투여라는 공통점만으로 연구 결과를 합치지 않는다. 선행치료 뒤 잔존 침윤암을 선별해 약제를 바꾸는 전략, 절제 후 보조요법의 구성을 대체하는 전략, 트라스투주맙 치료를 마친 뒤 추가하는 전략은 서로 다른 질문이다. 작은 종양의 단일군 보조요법 성적이나 수술 전 병용요법 비교도 모집 조건과 설계를 구분해 연결한다. 각 시험의 직접 비교는 인정하되 시험 사이의 수치 차이로 약제 순위를 정하거나 모든 조기 유방암으로 효과를 확대하는 판단은 보류한다.", "basis": [ { "claim": "캐서린은 선행 항암·표적치료 뒤 잔존 침윤암이 있는 집단에서 트라스투주맙 엠탄신과 트라스투주맙을 비교했고, 침윤성 무질병생존과 후속 생존 개선을 보고했다.", "units": [ "U-KATHERINE" ] }, { "claim": "카이틀린은 잔존암을 조건으로 선별한 시험이 아니라 절제된 고위험 집단의 보조요법 구성을 비교했다. 침윤성 무질병생존 개선이 없었으며, 배정된 약제의 완료 비율과 안전성도 함께 살펴야 한다.", "units": [ "U-KAITLIN" ] }, { "claim": "엑스티넷은 항암·트라스투주맙 치료 뒤 추가 네라티닙과 위약을 비교했다. 침윤성 무질병생존의 개선과 달리 최종 전체 생존 이득은 입증되지 않았고, 예방적 처치가 없던 조건에서 중증 설사가 더 빈번했다.", "units": [ "U-ExteNET" ] }, { "claim": "에이피티는 작은 종양과 주로 림프절 음성인 집단에서 파클리탁셀·트라스투주맙 보조요법을 관찰한 단일군 연구다. 제한된 림프절 미세전이가 허용됐으므로 엄격한 림프절 음성만의 결과로 쓰지 않는다. 장기 침윤성 무질병생존과 재발 관련 지표는 서로 다르며, 유리한 성적이 다른 요법과의 우월성이나 비열등성을 입증하지는 않는다.", "units": [ "U-APT" ] }, { "claim": "트레인 투는 2·3기 허투 양성 유방암에서 이중 표적치료와 함께 쓰는 수술 전 항암 구성을 비교했다. 일차 병리학적 완전반응에서 유의한 차이를 확인하지 못했고 이후 생존 추적은 이차 분석이었다. 수술 후 잔존암 선별이나 치료 완료 뒤 추가 투여와는 다른 질문이며, 음성 우월성 결과를 동등성으로 바꾸지 않는다.", "units": [ "U-TRAIN2" ] } ], "objection": "같은 표적과 겹치는 약제를 다뤄 생물학적 연결은 가능하다. 그러나 대조군, 이전 치료, 등록 시점과 위험 수준이 다르면 결과 차이를 특정 약제의 일반적인 우열로 해석할 수 없다. 한 시험의 실패가 다른 조건에서 얻은 직접 비교 이득을 무효로 만들지도 않는다.", "changesMind": "같은 이전 치료와 위험 조건에서 전략을 직접 비교한 결과가 공개되면 관계를 다시 판단한다. 새로운 치료를 거친 환자에게 확장하려면 그 치료 이력이 포함된 근거가 필요하며, 시험 간 단순 수치 비교만으로는 판단을 바꾸지 않는다.", "next": [ "선행치료 여부, 잔존 침윤암 조건, 이전 표적치료와 비교약을 각 연구에 나란히 기록한다", "재발 관련 효과와 전체 생존, 배정 약제 완료 및 중증 위해를 구분해 후속 결과를 확인한다", "저위험 단일군 관찰과 더 높은 병기의 선행 무작위 연구를 별도 맥락으로 표시하고, 대상 선별과 비교 설계 차이를 먼저 확인한다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-37", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-PERSEPHONE", "U-ShortHER", "U-APT", "U-TRAIN2", "U-HERA", "U-ATEMPT" ], "asOf": "2026-09-30", "status": "판단 기록됨", "title": "치료 축소는 무엇을 줄였는지부터 확인", "question": "허투 양성 조기 유방암에서 표적치료 기간이나 항암 구성을 줄인 연구와 저위험 집단의 단일군 성적을 하나의 치료 축소 성공으로 묶을 수 있는가?", "judgment": "축소한 요소와 검정 설계부터 구분한다. 같은 시험에서 사전에 정한 비열등성 경계를 충족한 결과는 그 대상군과 비교 조건 안에서 인정한다. 비열등성 실패는 비슷한 장기 생존 추정치나 유리한 탐색 하위군으로 뒤집지 않는다. 단일군 관찰과 음성 우월성 비교도 비열등성의 증거로 합치지 않으며, 시험 사이의 숫자로 최적 기간이나 약제 순위를 정하는 판단은 보류한다. 기간을 더 늘려도 이득이 없었다는 결과를 기간 축소의 비열등성으로 바꾸지 않는다. 세포독성 약제의 구성을 대체하는 전략도 치료 부담이 줄었는지와 비교 효능을 실제로 검정했는지 따로 확인한다.", "basis": [ { "claim": "퍼세포니는 트라스투주맙 6개월과 12개월을 비교했고, 4년 무질병생존의 절대 차이 3퍼센트포인트라는 사전 경계 안에서 비열등성을 보였다. 후속 보고에서도 이 결론을 유지했고 심장독성으로 인한 조기 중단은 짧은 군에서 적었다. 이는 완전한 동등성이나 모든 병용요법·위험 집단에서의 교환 가능성을 뜻하지 않는다.", "units": [ "U-PERSEPHONE" ] }, { "claim": "쇼트허는 9주와 1년의 전략을 비교했지만 일차 무질병생존의 신뢰구간 상한이 사전 비열등성 경계를 넘어 이를 입증하지 못했다. 장기 무질병생존과 전체 생존의 추정치가 비슷해도 이 결론은 유지된다. 항암 일정과 용량도 달랐고 모집 부족으로 검정력이 제한됐으므로 기간만의 효과나 탐색 하위군의 확정적 이득으로 읽지 않는다.", "units": [ "U-ShortHER" ] }, { "claim": "에이피티의 장기 성적은 작은 종양과 주로 림프절 음성인 집단을 관찰한 단일군 결과다. 더 강한 요법과 직접 비교하지 않았으므로 그 성적으로 기간 축소나 약제 생략의 비열등성을 입증할 수 없다.", "units": [ "U-APT" ] }, { "claim": "트레인 투는 이중 표적치료와 병용하는 수술 전 항암 구성에서 안트라사이클린을 포함한 전략과 포함하지 않은 전략을 비교했다. 일차 병리학적 완전반응의 유의한 차이가 없고 후속 생존 성적이 비슷하다는 사실을 사전 비열등성 검정의 성공으로 기록하지 않는다.", "units": [ "U-TRAIN2" ] }, { "claim": "헤라는 항암요법 뒤 트라스투주맙 1년의 관찰군 대비 장기 무질병생존·전체 생존 이득을 보였지만, 2년 투여가 1년보다 무질병생존을 더 개선하지는 못했다. 기간 비교는 366일 기준시점 분석이었고 관찰군의 선택적 교차 투여도 있었다. 이 결과는 1년보다 짧은 기간의 비열등성을 직접 검정한 것이 아니다.", "units": [ "U-HERA" ] }, { "claim": "아템프트는 1기 허투 양성 유방암에서 트라스투주맙 엠탄신과 파클리탁셀·트라스투주맙을 비교했으나, 공동 일차 목표인 임상적으로 중요한 독성의 감소를 입증하지 못했다. 엠탄신군의 침윤성 무질병생존 목표는 사전 기준값과 비교한 것이며 두 군의 효능 우월성이나 비열등성을 확정하도록 설계되지 않았다. 양호한 장기 성적이나 일부 환자 보고 지표로 독성 비교의 결과를 대신하지 않는다.", "units": [ "U-ATEMPT" ] } ], "objection": "치료 부담과 심장 위해를 줄이려는 목적은 중요하며, 장기 추적과 위해 감소는 축소 전략을 연구할 이유가 된다. 그러나 서로 다른 기간, 항암 구성과 위험 집단을 묶으면 어떤 요소를 줄여 얻은 결과인지와 허용한 불확실성을 가릴 수 있다.", "changesMind": "대상군과 이전 치료를 맞추고 축소할 요소를 명확히 한 직접 비교에서 사전 비열등성 경계, 충분한 추적과 위해 평가가 함께 충족되면 그 조건에 한해 판단을 넓힌다. 전체군 검정 실패를 탐색 하위군이나 생존율의 단순 유사성만으로 바꾸지는 않는다.", "next": [ "투여기간·항암 구성·모집 위험 수준 중 무엇을 바꿨는지와 비열등성 경계의 단위·신뢰구간 수준을 함께 기록한다", "효능 분석 집단과 실제 치료 안전성 분모를 구분하고, 중단·심장 위해·장기 재발을 같은 시험의 추적에 연결한다", "기간 연장 비교, 기간 단축의 비열등성 검정, 약제 구성 대체의 독성 비교와 단일군 기준값 평가를 서로 다른 설계로 표시한다" ], "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-38", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-PRODIGE23", "U-PROSPECT", "U-MOSAIC", "U-RAPIDO" ], "asOf": "2026-09-30", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "title": "직장암 전략의 강화와 생략을 구분함", "question": "수술 가능한 직장암에서 수술 전 항암요법을 강화한 결과와 방사선을 선택적으로 사용한 결과를 하나의 치료 강화 또는 축소 결론으로 합칠 수 있는가?", "judgment": "무작위 배정한 전체 전략과 모집 조건을 구분해 판단한다. 수술 전 항암 강화 전략의 이득은 그 비교 안에서 인정하고, 선택적 방사선 전략의 비열등성은 사전에 정한 범위 안에서 인정한다. 두 시험을 직접 비교해 최적 전략을 정하거나 방사선·수술을 모두 생략해도 된다는 판단으로 넓히지 않는다. 결장암 보조요법의 병기별 성적은 직장암의 생략 전략을 검증한 근거로 쓰지 않는다. 복합 평가변수나 원격 전이가 개선돼도 국소 재발이 같은 방향으로 변했다고 가정하지 않고, 각 사건과 분석 분모를 따로 확인한다.", "basis": [ { "claim": "프로디주 이십삼은 원격 전이가 없고 전신 상태가 양호하며 임상적 원발 종양 범주가 티 삼 또는 티 사인 직장암에서 선행 복합항암요법 뒤 화학방사선요법·수술·짧은 보조항암요법을 시행하는 전략과, 화학방사선요법·수술·더 긴 보조항암요법을 비교했다. 일차 무질병생존과 장기 추적의 이차 전체 생존 이득을 보고했지만 수술 전후 항암 노출이 함께 달라, 특정 약제 하나의 추가 효과나 방사선·수술 생략의 근거로 읽지 않는다.", "units": [ "U-PRODIGE23" ] }, { "claim": "프로스펙트는 괄약근 보존 수술이 가능한 특정 국소 병기의 직장암에서 선행 폴폭스와 선택적 화학방사선요법을 통상 화학방사선요법과 비교했다. 무질병생존의 사전 비열등성 기준을 충족했지만 종양 축소가 충분하지 않거나 항암요법을 견디지 못하면 방사선을 사용했고, 일부는 수술 뒤에도 방사선을 받았다. 모든 환자의 방사선 생략이나 수술 생략을 시험한 결과가 아니다.", "units": [ "U-PROSPECT" ] }, { "claim": "프로스펙트의 환자 보고 증상 자료는 전체 무작위 집단보다 작은 집단에서 얻었고, 증상과 기능 차이는 치료 시기에 따라 달랐다. 전체 건강 관련 삶의 질의 군 간 차이가 없었다는 결과를 모든 증상이나 부담이 동등하다는 뜻으로 바꾸지 않는다.", "units": [ "U-PROSPECT" ] }, { "claim": "모자이크는 절제한 2·3기 결장암의 수술 후 항암 구성을 비교한 별도 연구다. 장기 전체 생존 이득은 전체 및 3기 분석에서 보고됐지만 2기 분석에서는 입증되지 않았고, 병기별 유의성 차이만으로 병기와 치료의 상호작용을 확정할 수 없다. 이 결과를 직장암의 방사선이나 수술 생략 근거에 합치지 않는다.", "units": [ "U-MOSAIC" ] }, { "claim": "라피도는 영상에서 고위험으로 선별된 국소 진행 직장암에서 짧은 방사선요법 뒤 항암요법과 수술을 시행한 전략을 긴 화학방사선요법·수술 및 선택적 수술 후 항암요법과 비교했다. 초기 질병 관련 치료 실패의 감소와 후속 원격 전이 감소가 유지됐지만, 육안적 잔존암 없이 절제한 집단의 국소·구역 재발은 더 많았다. 전체 국소·구역 실패 비교의 유의하지 않은 결과로 절제 후 재발의 증가를 감추지 않는다.", "units": [ "U-RAPIDO" ] }, { "claim": "라피도의 초기 적격 집단, 후속 국소·구역 실패 평가 집단, 육안적 잔존암 없이 절제한 집단은 분모가 다르다. 치료 실패 복합지표는 전체 생존이 아니며, 방사선 일정과 항암 시점이 함께 다른 전체 전략의 결과를 한 요소의 효과로 분리하거나 방사선·수술 생략에 적용하지 않는다.", "units": [ "U-RAPIDO" ] } ], "objection": "치료의 순서와 노출을 조정하려는 직장암 시험들을 함께 검토하면 후속 연구 질문을 정하는 데 도움이 된다. 그러나 모집한 병기와 수술 가능 조건, 비교군과 검정 목적이 달라 한 시험의 이득을 다른 시험에서 생략한 요소의 안전성으로 옮길 수는 없다.", "changesMind": "같은 병기와 수술 조건에서 전략을 직접 비교하고 사전 효능 기준, 국소·원격 재발, 구제치료와 환자 보고 위해를 함께 평가한 자료가 확보되면 해당 조건에서 관계를 다시 판단한다. 수술 생략은 이를 직접 평가한 근거로 별도 검토한다.", "next": [ "각 시험의 임상 병기, 전신 상태, 수술 조건과 방사선 추가 기준을 나란히 기록한다", "무작위 배정·치료 개시·환자 보고 집단의 분모를 구분하고, 전체 전략의 효과와 특정 요소의 효과를 따로 표시한다", "결장 보조요법의 병기별 결과와 직장암 수술 전후 전략을 분리해 연결하고, 같은 시험의 장기 추적은 중복 집계하지 않는다", "치료 실패 복합지표를 국소·원격 사건으로 나누고, 절제 상태별 분모와 후속 재발 양상을 같은 시험 안에서 확인한다" ], "holdStatus": "not_flagged" }, { "id": "QP-39", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-ATTRACTION2", "U-INTEGRATE2A" ], "asOf": "2026-09-30", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "title": "생존 연장과 삶의 질은 따로 평가한다", "question": "여러 차례 치료를 받은 진행성 위암에서 전체 생존이나 건강 상태 악화까지의 복합지표가 개선되면, 환자가 실제로 느끼는 증상과 삶의 질도 좋아졌다고 기록할 수 있는가?", "judgment": "전체 생존, 악화·진행·사망을 함께 센 복합지표, 반복 측정한 증상과 삶의 질을 각각 판정한다. 위약 대조에서 확인된 생존 이득은 남기되 이를 증상 개선이나 다른 활성 치료보다 우월하다는 뜻으로 확대하지 않는다. 같은 연구의 삶의 질 후속 보고는 별도 질문에 대한 근거로 연결하고 독립 시험이나 재현으로 세지 않는다.", "basis": [ { "claim": "어트랙션 투는 이전 면역관문 치료를 받지 않고 두 가지 이상의 항암요법을 거친 동아시아의 절제 불가능한 진행성 또는 재발 위암·위식도접합부암에서 니볼루맙과 위약을 비교했다. 장기 추적에서도 전체 생존 이득을 보였지만 치료 관련 중증 이상반응과 사망도 보고됐다. 진행 뒤 계속 치료한 집단의 성적은 선택된 관찰이므로 지속 투여의 인과적 이득이나 이전 면역치료 뒤 효과로 확대하지 않는다.", "units": [ "U-ATTRACTION2" ] }, { "claim": "인티그레이트 후속 삼상 시험은 이전 두 가지 이상의 치료를 받은 위암 또는 위식도접합부암에서 레고라페닙과 최선의 지지요법을 위약과 지지요법에 비교했다. 앞선 연구와의 통합 검정을 먼저 시행한 뒤 이 연구 자체의 전체 생존 이득도 확인했다. 연구별 결과와 통합 추정치를 같은 수치나 별도의 재현으로 합치지 않는다.", "units": [ "U-INTEGRATE2A" ] }, { "claim": "같은 연구의 삶의 질 보고는 251명 중 240명의 자료를 포함했다. 전반적 건강 상태의 악화 없는 생존은 건강 상태 악화뿐 아니라 진행이나 사망도 사건으로 세는 복합지표였고, 레고라페닙군에서 개선됐다. 반면 반복 측정한 삶의 질의 변화 양상에서는 뚜렷한 차이가 없었으며 여러 증상·부작용과 대처의 어려움은 더 자주 보고됐다. 복합지표의 개선만으로 실제 증상이나 삶의 질이 좋아졌다고 쓰지 않는다.", "units": [ "U-INTEGRATE2A" ] } ], "objection": "사망이나 질병 진행을 늦추면서 건강 상태를 유지하는 결과도 가치가 있으므로 복합지표를 무의미하다고 볼 수는 없다. 다만 그 지표가 좋아진 이유와 환자가 경험한 부담은 다른 질문이며, 평균 변화에 뚜렷한 차이가 없다는 사실도 모든 환자의 경험이 같다는 뜻은 아니다.", "changesMind": "사전에 정한 환자 보고 평가에서 임상적으로 의미 있는 증상 또는 삶의 질 차이가 확인되고, 사망·진행과 응답 누락의 처리 및 추적기간을 검토할 수 있으면 해당 경험의 개선을 별도로 판단한다. 다른 활성 치료와의 우열은 직접 비교하거나 비교 가능성이 검토된 근거가 있어야 판단한다.", "next": [ "생존·복합 악화 지표·개별 증상·삶의 질 척도의 사건 정의와 분석 분모를 각각 기록한다", "환자 보고 자료의 수집 시점, 응답 누락과 사망 뒤 자료 처리, 치료 중단 및 중증 위해를 원래 시험과 연결한다", "이전 면역치료, 지역과 치료 차수, 위약 또는 활성 대조군의 차이를 확인한 뒤 후속 연구 질문을 정한다" ], "holdStatus": "not_flagged" }, { "id": "QP-40", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-TAILORx", "U-RxPONDER", "U-MINDACT" ], "asOf": "2026-09-30", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-09-30", "updatedBy": "Codex (GPT-6)", "title": "재발 위험 점수와 항암 이득은 다르다", "question": "조기 유방암의 유전자 점수가 재발 위험을 설명하면, 같은 점수를 가진 모든 환자의 항암치료 이득이나 생략 가능성도 같다고 볼 수 있는가?", "judgment": "위험 예측과 치료 이득의 예측을 구분하고, 직접 비교한 환자 범위와 검정 질문 안에서 판단한다. 림프절 상태, 점수 범위와 폐경 상태가 다른 집단을 하나의 생략 규칙으로 합치지 않는다. 전체군의 비열등성, 항암치료를 받지 않은 군의 사전 성적 기준, 치료와 환자 특성 사이의 상호작용은 서로 다른 근거다. 나이와 폐경 상태를 바꾸어 쓰거나 탐색 결과로 개인의 치료 이득을 확정하는 판단은 보류한다.", "basis": [ { "claim": "테일러엑스는 호르몬 수용체 양성·허투 음성이고 겨드랑이 림프절이 음성인 집단 중 재발 점수 11~25에서 내분비요법 단독과 항암 병용을 무작위 비교했다. 일차 침윤성 무질병생존의 비열등성을 보였지만 나이와 점수를 함께 본 탐색 결과는 일부 젊은 집단의 이득 가능성을 남겼다. 그 밖의 점수 집단은 같은 무작위 비교를 받지 않았으므로 모든 점수나 젊은 환자 전체의 생략 근거로 확대하지 않는다.", "units": [ "U-TAILORx" ] }, { "claim": "알엑스폰더는 같은 수용체 조건에서 겨드랑이 림프절 1~3개 양성이고 재발 점수가 25 이하인 여성을 비교했다. 사전 중간 분석에서 항암 이득은 폐경 상태에 따라 달랐고 상호작용이 보고됐다. 폐경 전에는 침윤성 무질병생존과 원격 재발 없는 생존이 개선됐지만 폐경 후에는 항암 추가 이득이 입증되지 않았다. 시험 범위 안에서 점수가 높을수록 상대 이득이 커진 것도 아니었다.", "units": [ "U-RxPONDER" ] }, { "claim": "민닥트의 임상 고위험·유전체 저위험 집단은 항암치료 없이 지낸 일차 검정 집단의 원격 전이 없는 생존이 사전 기준을 넘었다. 그러나 별도의 장기 무작위 비교에서는 항암치료군의 성적이 더 좋았다. 기준 충족을 두 치료의 동일한 결과로 바꾸지 않으며, 호르몬 수용체 양성·허투 음성 하위집단의 나이별 분석은 검정력이 부족한 탐색 결과로 남긴다.", "units": [ "U-MINDACT" ] }, { "claim": "젊은 환자에서 나타난 항암 이득을 난소기능 억제만의 효과로 확정할 수는 없다. 알엑스폰더는 항암치료와 최적화한 난소기능 억제를 직접 무작위 비교하지 않았으며, 후속 난소 예비력 표지자 분석도 저장 혈청이 있는 일부 집단의 분석이다. 표지자로 치료를 정하는 정책이 독립적으로 검증된 결과와는 구분한다.", "units": [ "U-RxPONDER", "U-MINDACT" ] }, { "claim": "테일러엑스 후속 자료에서 임상 위험과 유전자 점수를 결합한 모형의 예후 정보를 평가한 것은 새로운 무작위 치료 비교가 아니다. 후기 재발을 예측하는 성능만으로 특정 연장 내분비요법의 이득까지 입증하지 않는다.", "units": [ "U-TAILORx" ] } ], "objection": "유전자 점수와 임상 정보는 위험을 나누고 비교 연구의 대상을 정하는 데 유용하다. 그러나 위험이 낮은 집단의 좋은 성적, 위험 예측 모형의 외부 평가, 무작위 치료 효과는 서로 대체할 수 없으며 생략으로 감수하는 불확실성도 같은 방식으로 측정되지 않는다.", "changesMind": "같은 림프절·폐경·점수 조건에서 사전에 정한 표지자와 치료의 상호작용 및 표지자 기반 전략의 환자 결과가 독립적으로 확인되면 적용 범위를 갱신한다. 젊은 집단의 기전을 구분하려면 난소기능 억제와 항암 기여를 직접 평가한 비교 근거가 필요하다.", "next": [ "각 시험의 등록 집단·실제 무작위 집단·일차 검정 집단을 구분하고 점수 범위와 폐경 또는 나이 기준을 기록한다", "예후 연관성, 치료와 표지자의 상호작용, 표지자 기반 전략의 임상적 유용성을 별도 항목으로 관리한다", "침윤성 무질병생존·원격 전이 또는 재발 없는 생존·전체 생존을 나누고, 탐색 하위군과 후기 예후 모형은 원래 시험에 연결한다" ], "holdStatus": "held" }, { "id": "QP-41", "program": "gastric", "targets": [ "FGFR2" ], "biomarkers": [], "units": [ "U-FIGHT", "U-FORT101" ], "asOf": "2026-10-01", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-09-30", "updated": "2026-10-01", "updatedBy": "Muse Spark1.3; reviewed by Gemini Flash3.8; integrated by Codex (GPT-6)", "title": "고발현 하위군만으로 성공을 정하지 않음", "question": "허투 비양성 진행성 위암의 수용체 표적치료 2상 시험에서 고발현 하위군의 결과가 더 좋으면 전체 시험의 성공과 유전자 증폭 검사의 치료 선별 능력까지 확정할 수 있는가?", "judgment": "보고 시점과 검정 기준, 전체군과 고발현 하위군을 구분한다. 파이트의 일차 논문 해석과 공개 통계분석계획을 함께 읽고, 정식 가설검정을 하지 않은 최종 추적을 새로운 확증 검정으로 세지 않는다. 별도 삼상인 포티튜드 백일의 학회 초록은 사전에 정한 고발현 집단에서 일차 중간 전체 생존 검정의 성공을 보고했다. 이후 기술적 추적의 효과 약화는 새 정식 실패 검정이 아니지만, 이득의 지속성과 위해를 평가할 때 함께 고려한다. 두 시험을 합쳐 검사 교환 가능성이나 모든 환자의 치료 이득을 확정하지 않는다.", "basis": [ { "claim": "파이트의 등록 기준은 중앙 면역조직화학 검사에서 섬유아세포 성장인자 수용체 이 비의 과발현 또는 혈액 순환 종양 디엔에이 검사에서 수용체 이 유전자의 증폭, 또는 둘 모두였다. 허투 비양성 진행성 위암·위식도접합부암에서 베마리투주맙과 항암 병용을 위약과 같은 항암 병용에 비교했다. 2022년 일차 논문은 무진행생존의 개선을 통계적으로 유의하지 않다고 기술했다. 한편 공개된 2020년 10월 통계분석계획에는 무진행생존을 먼저 검정한 뒤 전체 생존과 반응률을 순서대로 검정하는 단측 0.1 기준이 적혀 있다. 두 기술을 구분하며 통상적인 0.05 기준만으로 일차 평가변수 실패를 단정하지 않는다. 최종 추적은 정식 가설검정을 하지 않았고, 전체군 무진행생존과 전체 생존 위험비의 신뢰구간은 차이 없음의 값을 포함했다.", "units": [ "U-FIGHT" ] }, { "claim": "최종 보고에서 수용체 이 비의 중간 또는 강한 세포막 염색인 이 플러스 또는 삼 플러스가 종양세포의 10퍼센트 이상에서 확인된 하위군은 더 유리한 효과 추정치를 보였다. 최종 논문은 이를 사전에 정한 탐색적 하위군 분석으로 설명하며, 확증적 선별 검증과는 구분한다. 이 결과를 유전자 증폭 검사와 동일한 환자를 고른다는 증거로 쓰거나, 선별 기준에 따른 치료 정책의 독립 검증으로 기록하지 않는다.", "units": [ "U-FIGHT" ] }, { "claim": "최초 안전성 분석은 실제 배정 약제를 투여받은 집단에서 이뤄졌고 베마리투주맙군에서 각막 이상반응과 중증 각막 사건이 더 많이 보고됐다. 최종 자료를 이용한 사후 삶의 질 분석의 평균 변화가 비슷했다는 결과로 안구 위해를 지우거나 삶의 질의 동등성을 입증했다고 쓰지 않는다.", "units": [ "U-FIGHT" ] }, { "claim": "포티튜드 백일의 학회 초록에서는 사전에 정한 고발현 집단의 일차 중간 전체 생존 분석이 효능 경계를 넘었고 배정된 유의수준을 모두 사용했다고 보고했다. 이후 더 긴 추적은 기술적 분석이며 효과 추정치가 약해지고 신뢰구간이 차이 없음의 값을 포함했다. 이는 일차 검정의 성공을 새로운 정식 실패로 바꾸는 결과는 아니며, 효과 크기와 지속성의 불확실성을 남긴다. 일차 효과 집단은 중간 또는 강한 염색이 종양세포의 십퍼센트 이상에서 확인된 집단으로, 전체 등록자와 구분한다. 안전성은 실제 투여 치료에 따라 분석한 집단이며, 중증 치료 중 발생 이상반응의 증가는 주로 각막 이상반응에 기인한다고 초록은 설명했다. 현재 등록자료와 초록의 등록 기준 차이는 아직 대조를 마치지 못했다. 이 기록의 원출처 검토 범위는 학회 초록과 표, 등록자료이며 전체 논문이나 발표자료의 검토를 뜻하지 않는다.", "units": [ "U-FORT101" ] } ], "objection": "표적 발현이 높은 집단에서 더 큰 효과가 관찰되면 기전과 연결되는 유망한 선별 가설이 될 수 있다. 그러나 하위군 크기와 분석 계획, 다중 비교 및 검사 재현성을 확인하지 않고 유리한 결과만 선택하면 효과를 과대평가할 수 있다.", "changesMind": "현재의 일차 생존 검정 성공과 이후 효과 약화를 함께 유지하며, 전체 보고와 분석계획·등록 기준 변경 이력을 대조해 효과의 지속성과 안전성 판단을 갱신한다. 유전자 증폭 검사를 대체 기준으로 쓰려면 두 검사의 환자 분류와 치료 이득에 대한 별도 검증이 필요하다. 항암·면역 병용과의 우열이나 별도 후속 시험의 효능은 해당 원출처가 확보되어야 판단한다.", "next": [ "원래 등록 조건과 고발현 하위군의 염색 강도·양성 세포 비율·분석 계획을 나누어 기록한다", "전체군과 하위군의 효과 구간, 실제 치료 안전성 분모와 각막 위해를 같은 시험 안에 남긴다", "파이트의 후속 보고는 원시험에 연결하고 포티튜드 백일은 별도 시험으로 유지하며, 전체 보고·검사 기준 변경 이력·각막 위해의 경과를 추가 대조한다" ], "holdStatus": "not_flagged" }, { "id": "QP-42", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-GastricAdjuvantIC26", "U-MATTERHORN", "U-ATT5" ], "asOf": "2026-10-02", "status": "판단 기록됨", "title": "수술 뒤 면역치료 생략은 아직 미결", "question": "수술 전 면역항암 병용을 받은 위암 환자에서, 성향점수를 맞춘 관찰연구가 수술 후 면역치료의 생존 차이를 찾지 못하면 생략의 안전성을 인정할 수 있는가?", "judgment": "수술 후 치료를 따로 비교해야 한다는 연구 질문은 구체화됐지만 생략 판단은 보류한다. 관찰자료에서 유의한 차이가 없다는 결과는 두 전략의 동등성이나 비열등성 증명이 아니다. 수술 전후 전체 전략의 무작위 시험도 수술 후 성분의 기여를 단독으로 분리하지 못한다.", "basis": [ { "claim": "새 위암 관찰연구는 성향점수로 짝지은 수술 후 두 집단에서 무병생존과 전체 생존의 유의한 차이를 찾지 못했고, 면역항암제를 함께 쓴 집단에서 면역 관련 이상반응을 더 많이 보고했다. 짝맞춤 이후에도 치료 선택과 평가 시작 시점의 편향은 별도 확인이 필요하다.", "units": [ "U-GastricAdjuvantIC26" ] }, { "claim": "수술 전후 두르발루맙 병용의 무작위 비교는 전체 전략의 무사건생존과 최종 전체 생존 이득을 보고했지만 수술 전과 후의 기여를 따로 배정한 시험은 아니다. 따라서 관찰연구와 질문이 같지 않다.", "units": [ "U-MATTERHORN" ] }, { "claim": "수술을 먼저 받은 집단의 니볼루맙 보조요법 시험은 재발 없는 생존의 개선을 입증하지 못했다. 이 결과도 수술 전 면역치료를 이미 받은 집단의 생략 효과를 직접 보여주지는 않는다.", "units": [ "U-ATT5" ] } ], "objection": "비슷한 생존 추정치와 더 잦은 면역 관련 이상반응은 치료 축소를 검토할 현실적인 단서다. 다만 치료를 이어갈 수 있었던 환자와 중단하거나 받지 않은 환자의 차이를 완전히 제거하지 못하면 이득과 위해 모두 왜곡될 수 있다.", "changesMind": "수술 전 치료와 수술 후 배정 시점이 명확하고, 생략의 허용 손실·통계 검정·장기 추적·중증 위해를 미리 정한 무작위 비교가 확보되면 판단을 갱신한다. 현재 관찰연구의 전문과 시간 기준·매칭 변수부터 확인한다.", "next": [ "성향점수에 넣은 변수와 수술 후 치료 선택 시점, 생존 추적의 시작점을 원문에서 대조한다", "관찰연구의 신뢰구간·중증 위해와 치료 중단 사유를 확인하고 무작위 시험과 분리해 기록한다" ], "by": "Codex (GPT-6)", "added": "2026-10-02", "holdStatus": "held" }, { "id": "QP-43", "program": "breast", "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "units": [ "U-evERA", "U-VERITAC2", "U-SERENA6" ], "asOf": "2026-10-02", "status": "판단 기록됨", "title": "변이군의 진행 지연과 약제 순위는 별개", "question": "이전 세포주기 억제제 치료 뒤 수용체 분해제와 에베로리무스 병용이 진행을 늦췄다면, 수용체 유전자 변이로 모든 분해제의 우열과 최적 치료 순서를 정할 수 있는가?", "judgment": "같은 에베로리무스 배경에서 비교한 진행 지연은 해당 시험의 결과로 인정한다. 변이군과 그 집단을 포함하는 전체군의 검정을 독립 재현으로 세지 않고, 변이가 효과 차이를 예측한다는 상호작용 검증이나 다른 분해제와의 우열로 확대하지 않는다.", "basis": [ { "claim": "에베라 시험은 에스트로겐 수용체 양성·HER2 음성 진행성 유방암에서 기존 세포주기 억제제와 내분비치료 후 진행 또는 재발한 환자를 등록했다. 변이군을 먼저, 전체군을 다음으로 검정했고 같은 에베로리무스를 병용한 대조군보다 연구자 평가 무진행생존이 길었다.", "units": [ "U-evERA" ] }, { "claim": "베리탁 이의 분해제 비교는 풀베스트란트가 대조군이고 변이군과 전체군의 결과가 달랐다. 에베로리무스를 공통으로 사용한 새 시험과 효과 수치를 바로 비교해 약제 순위를 정할 수 없다.", "units": [ "U-VERITAC2", "U-evERA" ] }, { "claim": "세레나 육은 영상상 진행 전에 혈액에서 변이가 나타날 때 치료를 교체하는 전략이었다. 이미 진행하거나 재발한 뒤 병용요법을 시작하는 질문과 구분해야 한다.", "units": [ "U-SERENA6", "U-evERA" ] } ], "objection": "변이군의 뚜렷한 진행 지연은 후속 선별 가설을 지지할 수 있다. 그러나 전체군과 하위군의 중첩, 대조약과 병용 성분, 이전 치료가 다른 상황에서는 효과 크기의 차이가 곧 약제 자체의 차이라고 할 수 없다.", "changesMind": "변이 여부에 따른 치료 상호작용, 전체 생존과 중증 위해, 동등한 치료 맥락의 직접 비교가 검토되면 선별 범위와 치료 순서 가설을 갱신한다. 전체 이상반응 빈도가 비슷하다는 이유만으로 안전성 동등성을 인정하지 않는다.", "next": [ "원문에서 전체 생존의 성숙도와 분석집단별 중증 위해·중단 분모를 확인한다", "변이군의 사전 검정 순서와 상호작용 검정 여부를 구분하고 진행 전 교체 시험과 별도 표로 관리한다" ], "by": "Codex (GPT-6)", "added": "2026-10-02", "holdStatus": "held" }, { "id": "QP-44", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-NEO" ], "asOf": "2026-10-03", "status": "판단 기록됨", "title": "혈액 신호가 없어도 남는 직장암 절제 판단", "question": "수술 전 항암치료 뒤 혈액에서 종양 유래 신호가 검출되지 않으면 직장 절제의 필요성을 판단할 근거가 충분한가?", "judgment": "미검출을 잔존 종양 없음이나 절제 생략의 근거로 바꾸지 않는다. 새 분석에서는 미검출군에도 광범위 절제가 권고됐으며, 혈액 검사로 치료를 결정한 무작위 비교가 아니었다. 검사 기반 생략 전략의 안전성과 재발 검출 성능은 보류한다.", "basis": [ { "claim": "네오 시험의 혈액 분석에서는 항암치료 뒤 신호가 검출된 네 명 모두와 검출되지 않은 마흔두 명 중 열여섯 명에게 광범위 절제가 권고됐다. 권고 여부를 실제 수술 시행이나 잔존 종양 확진과 같은 결과로 세지 않는다.", "units": [ "U-NEO" ] }, { "claim": "재발 다섯 건 중 반복 혈액 표본이 있는 경우는 국소 재발 두 건뿐이었고, 진행 시 신호가 검출된 것은 그중 한 건이었다. 나머지 표본 공백을 음성으로 바꾸거나 전체 재발 검출 성능을 계산할 수 없다.", "units": [ "U-NEO" ] }, { "claim": "원시험은 수술 전 항암치료와 국소 절제를 평가한 단일군 연구였다. 종양 조직 없이 시행하는 검사라는 뜻과 종양이 없다는 판단은 구분해야 한다.", "units": [ "U-NEO" ] } ], "objection": "혈액 신호와 불충분한 반응의 연관성은 다른 평가와 결합할 가설을 뒷받침할 수 있다. 다만 소수의 검출 사례와 표본 누락이 있는 분석만으로 검사 단독의 결정 기준을 확정할 수 없다.", "changesMind": "검사 기준과 채혈 시점이 고정된 독립 집단에서 임상·영상·병리 평가에 추가되는 가치가 확인되고, 검사에 따른 개입 전략이 재발과 장기 기능을 비교한 결과가 나오면 생략 가설을 다시 검토한다.", "next": [ "허용된 전문 접근이 생기면 시점별 표본 분모와 누락 이유, 검사 임계값을 확인한다", "검사 결과가 실제 치료 결정 전에 알려졌는지 확인하고, 절제 권고·시행·병리 결과를 분리한다" ], "by": "Codex (GPT-6)", "added": "2026-10-03", "holdStatus": "held" }, { "id": "QP-45", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-FAHCDK9" ], "asOf": "2026-10-03", "status": "판단 기록됨", "title": "핵으로 옮겨간 단백질과 내성 가설의 거리", "question": "대사 효소의 핵 이동과 결합을 설명하는 구조 예측은 유방암 내성을 겨냥한 치료 가설을 어디까지 뒷받침하는가?", "judgment": "이 연구의 가치는 구조 후보를 제시한 뒤 결합 부위 변형과 기능 실험으로 가설을 좁힌 절차에 있다. 환자 유래 모형에서의 내성 변화는 전임상 근거로 기록하고, 핵 내 단백질을 이용한 환자 선별과 병용치료 이득은 보류한다.", "basis": [ { "claim": "새 연구는 치료 뒤 대사 효소의 핵 이동과 다른 단백질의 상호작용을 내성에 연결했고, 재발 환자 종양에서 핵 내 축적의 연관성을 보고했다. 연관성만으로 임상 선별검사가 검증된 것은 아니다.", "units": [ "U-FAHCDK9" ] }, { "claim": "원문은 구조 예측으로 결합 후보를 정한 뒤 변형 실험과 기능 회복을 확인했다. 예측된 모양의 일치만으로 내성 기전이 입증됐다고 해석하지 않는다.", "units": [ "U-FAHCDK9" ] }, { "claim": "병용 실험은 해당 단백질을 과발현한 환자 유래 오가노이드에서 수행됐다. 연구진도 추가 모형과 생체 내 효과·안전성 확인을 남겼으므로 환자의 치료 이득으로 옮기지 않는다.", "units": [ "U-FAHCDK9" ] } ], "objection": "여러 기능 실험과 환자 종양의 관찰이 같은 방향을 가리켜 후속 검증의 우선순위를 높일 수 있다. 그러나 과발현 모형의 취약점이 자연 상태의 다양한 내성 종양에서 유지되는지는 별도 질문이다.", "changesMind": "자연적으로 핵 내 축적이 높은 독립 모형에서 상호작용의 필요성과 약제 반응이 재현되고, 환자 선별 기준 및 비교 임상 결과가 확보되면 치료 가설의 준비도를 다시 평가한다.", "next": [ "핵 내 위치와 총발현량을 구분해 측정할 자료와 이용조건을 확인한다", "결합을 깨는 조작의 기능 회복과 독립 모형의 재현 결과를 후속 확인한다" ], "by": "Codex (GPT-6)", "added": "2026-10-03", "holdStatus": "held" }, { "id": "QP-46", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-P53CRLM26" ], "asOf": "2026-10-04", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-04", "title": "간 전이 절제 후 조직검사로 읽는 재발 위험", "question": "항암치료 후 간 전이를 절제한 환자의 단백질 염색 소견이 재발 위험을 구분해도 치료 선택까지 바꿀 근거가 되는가?", "judgment": "병리학적 완전반응이 없었던 선택된 집단의 예후 연관성으로 기록한다. 검사에 따른 치료 변경의 이득은 보류한다.", "basis": [ { "claim": "전향 관찰 연구에서 수술 후 염색 이상은 짧은 무재발생존과 연관됐지만, 검사 기반 치료 전략을 비교하지 않았다.", "units": [ "U-P53CRLM26" ] } ], "objection": "치료 후 조직이 남은 위험을 포착할 가능성은 있으나 작은 표본과 환자 선택의 영향을 분리해야 한다.", "changesMind": "독립 집단의 예측 성능과 검사 기반 개입의 비교 결과가 확보되면 치료 선택 가설을 다시 평가한다.", "next": [ "원문의 재발 사건 수와 보정 변수를 확인한다", "치료 전후 검사 시점과 독립 검증 여부를 대조한다" ], "holdStatus": "held" }, { "id": "QP-47", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-TFAMTBK1" ], "asOf": "2026-10-04", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-04", "title": "손상 소기관 청소가 항암제 내성을 돕는 조건", "question": "항암제 스트레스 뒤 손상된 소기관을 제거하는 경로를 막으면 대장암의 약제 감수성을 회복할 수 있는가?", "judgment": "세포·이식종양·환자 유래 오가노이드의 내성 기전 가설로 기록한다. 환자 선별과 병용치료의 임상 이득은 보류한다.", "basis": [ { "claim": "연구는 미토콘드리아 유전물질 유출과 손상 소기관 제거를 연결했고, 경로 억제 시 시험한 모형의 약제 반응 회복을 보고했다.", "units": [ "U-TFAMTBK1" ] } ], "objection": "모형의 취약점이 면역세포를 포함한 실제 종양에서도 유지되고 안전하게 억제되는지는 별도 검증이 필요하다.", "changesMind": "표적 선택성과 독립 모형의 재현, 노출·안전성 및 비교 임상 결과가 확보되면 치료 가설의 준비도를 다시 평가한다.", "next": [ "원문의 약제 선택성과 표적 조작 대조를 확인한다", "독립 모형과 면역세포 영향의 후속 근거를 찾는다" ], "holdStatus": "held" }, { "id": "QP-48", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-ILCLuminal26" ], "asOf": "2026-10-05", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-05", "title": "소엽암의 아형별 위험 차이는 아직 미결", "question": "한 아형에서만 소엽암의 불리한 예후가 유의하면 아형마다 위험 차이가 다르다고 결론 낼 수 있는가?", "judgment": "그렇게 결론 내리지 않는다. 전체 분석의 불확실성과 유의하지 않은 교호작용을 함께 남기고, 아형별 차이와 치료 이득 판단을 보류한다.", "basis": [ { "claim": "한 아형의 연관성은 유의했지만 조직형과 아형의 교호작용은 유의하지 않았다. 전체 수술 집단과 아형 분석의 분모도 구분해야 한다.", "units": [ "U-ILCLuminal26" ] } ], "objection": "아형별 차이가 실제로 있어도 표본 부족으로 교호작용을 놓쳤을 가능성은 남는다.", "changesMind": "충분한 표본의 독립 연구에서 교호작용과 추적 지표가 사전 계획대로 재현되면 다시 판단한다.", "next": [ "원문의 아형별 분모와 사건 수를 확인한다", "치료 선택의 교란과 보정 변수를 점검한다" ], "holdStatus": "held" }, { "id": "QP-49", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-Ki67Axilla26" ], "asOf": "2026-10-05", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-05", "title": "증식 지표의 변화와 수술 선택은 별개다", "question": "선행항암 뒤 증식 지표 감소와 예후의 연관성을 겨드랑이 수술을 선택하는 근거로 옮길 수 있는가?", "judgment": "옮기지 않는다. 초기 지표의 음성 결과와 잔존암 변화 분석의 검정별 불확실성을 기록하고 수술 선택의 유용성은 보류한다.", "basis": [ { "claim": "초기 지표는 림프절 완전반응이나 재발을 예측하지 못했다. 잔존암 분석은 신뢰구간에 차이 없음이 포함되고 검정별 유의성도 달랐다.", "units": [ "U-Ki67Axilla26" ] } ], "objection": "초기 값과 치료 후 변화는 다른 질문이므로 초기 음성 결과만으로 변화의 가치를 배제할 수 없다.", "changesMind": "측정 기준을 고정한 독립 검증과 검사 기반 수술 전략의 비교 결과가 확보되면 다시 평가한다.", "next": [ "분석 대상 분모와 검사 시점을 확인한다", "사전 검정과 재발 사건 수를 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-50", "program": "breast", "targets": [ "PDCD1" ], "biomarkers": [ "BM-PDL1-B" ], "units": [ "U-KN355", "U-IMP130", "U-IMP131" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "면역항암 이득은 검사 점수 구간에 한정한다", "question": "선별 점수가 높은 환자군에서 확인된 면역항암 병용의 생존 이득을 점수가 낮은 환자군이나 전체 환자로 넓혀 읽을 수 있는가?", "judgment": "넓혀 읽지 않는다. 사전에 정한 검정 순서에서 유의성이 확인된 구간까지만 이득으로 기록하고, 그보다 낮은 구간과 전체 환자의 이득은 보류한다.", "basis": [ { "claim": "삼중음성 유방암 1차 치료 시험에서 무진행생존과 전체생존의 유의성은 점수 10 이상 구간에서만 확인됐다. 점수 1 이상 구간은 기준을 넘지 못했고 전체 환자는 검정하지 않았다.", "units": [ "U-KN355" ] }, { "claim": "다른 면역항암제를 쓴 두 시험은 병용 항암제가 서로 달랐고 결과도 달랐다. 두 시험의 양성 판정이 이 시험의 점수 구간과 같다고 볼 근거는 없다.", "units": [ "U-IMP130", "U-IMP131" ] } ], "objection": "점수가 낮은 구간에서도 위험비가 1보다 작았으므로 표본이 더 컸다면 이득이 드러났을 가능성은 남는다.", "changesMind": "점수가 낮은 구간을 사전에 주분석으로 정한 무작위 시험에서 생존 이득이 확인되면 범위를 다시 정한다.", "next": [ "점수 구간별 환자 수와 사건 수를 원문에서 확인한다", "검사법 사이의 판정 일치도 자료를 찾는다" ], "holdStatus": "held" }, { "id": "QP-51", "program": "colorectal", "targets": [ "ERBB2" ], "biomarkers": [], "units": [ "U-MOUNTAINEER", "U-DCRC01", "U-DB04" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "대장암 HER2 표적 반응은 대조 없이 못 정함", "question": "대조군 없는 시험의 반응률만으로 대장암에서 HER2 표적치료의 비교 이득과 저발현 환자의 반응을 판단할 수 있는가?", "judgment": "판단하지 않는다. HER2 양성 대장암에서 반응이 관찰됐다는 사실만 기록하고, 표준치료 대비 생존 이득과 저발현 환자의 반응 여부는 보류한다.", "basis": [ { "claim": "두 시험 모두 HER2 양성 대장암에서 반응률을 보고했지만 표준치료와 비교하는 대조군이 없었다.", "units": [ "U-MOUNTAINEER", "U-DCRC01" ] }, { "claim": "발현이 낮은 두 환자군에서는 반응이 없었으나 각각 15명과 18명이었다. 유방암 저발현 환자의 생존 이득은 다른 암종의 결과다.", "units": [ "U-DCRC01", "U-DB04" ] } ], "objection": "표준치료에 실패한 뒤의 환자에서 반응률 40% 안팎은 기대 반응보다 높아, 대조군 없이도 활성 자체는 인정할 수 있다는 견해가 있다.", "changesMind": "HER2 양성 대장암에서 표준치료와 비교한 무작위 시험의 생존 결과가 공개되거나 저발현 환자를 충분히 포함한 결과가 나오면 다시 판단한다.", "next": [ "진행 중인 무작위 비교 시험의 등록 정보를 확인한다", "HER2 판정 기준이 위암·유방암과 어떻게 다른지 정리한다" ], "holdStatus": "held" }, { "id": "QP-52", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "units": [ "U-ML2", "U-NATALEE", "U-monarchE", "U-PALLAS", "U-PENELOPEB" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "같은 계열 약의 생존 성적을 서로 빌리지 않음", "question": "한 세포주기 억제제가 진행성 유방암에서 전체생존을 늘렸다면 같은 계열의 다른 약이나 조기 유방암에도 같은 이득을 기대할 수 있는가?", "judgment": "기대하지 않는다. 생존 이득은 그 약, 그 병기, 그 병용 조건의 결과로만 기록하고, 계열 전체의 효과로 묶는 해석은 보류한다.", "basis": [ { "claim": "진행성 1차 치료 시험에서 전체생존 이득이 사전에 정한 최종 분석으로 확인됐다. 대상은 폐경 후 환자와 한 가지 병용 약제였다.", "units": [ "U-ML2" ] }, { "claim": "조기 유방암에서는 같은 계열의 한 약이 두 시험에서 재발 지표를 개선하지 못했고, 다른 두 약은 개선을 보고했다. 진행성에서 생존을 늘린 바로 그 약은 조기 시험의 사전에 정한 6년 분석에서 전체생존 위험비 0.809(95% 신뢰구간 0.661–0.989)를 보고했고, 저자들은 이 분석을 기술적 분석으로 설명했다.", "units": [ "U-PALLAS", "U-PENELOPEB", "U-monarchE", "U-NATALEE" ] } ], "objection": "세 약은 같은 표적을 억제하므로 결과 차이는 약 자체보다 대상 환자, 투여 기간, 중단율의 차이에서 왔을 수 있다.", "changesMind": "같은 계열 약을 직접 비교한 무작위 시험이나 환자 수준 자료를 맞춘 비교에서 일관된 생존 결과가 나오면 다시 판단한다.", "next": [ "시험별 투여 기간과 중단율을 원문에서 확인한다", "진행 뒤 후속 치료의 차이를 정리한다" ], "holdStatus": "held" }, { "id": "QP-53", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-AutoimmuneThyCa24", "U-HashimotoOutcome21", "U-HashimotoPTC17", "U-KoreaThyScreen16" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "갑상선염이 암을 부르는지 막는지는 미정", "question": "하시모토 갑상선염 환자에서 갑상선암이 더 자주 진단되면서도 함께 있을 때 예후가 더 좋게 관찰된다면, 갑상선염이 암을 일으킨다거나 암의 진행을 막는다고 볼 수 있는가?", "judgment": "둘 다 결론 내리지 않는다. 갑상선염 환자에서 진단이 더 잦았고 동반 환자의 종양이 덜 진행된 상태였다는 두 연관성만 기록한다. 발병 원인이라는 해석과 보호 효과라는 해석은 모두 보류한다. 검사를 더 자주 받아 작은 암이 일찍 발견되면 두 관찰이 함께 나타날 수 있기 때문이다.", "basis": [ { "claim": "한국 건강보험 표본 코호트에서 하시모토 갑상선염 환자는 대조군보다 갑상선암이 새로 진단될 위험비가 높았다. 갑상선 밖의 자가면역 질환에서도 위험비가 높았고, 군별 갑상선 검사 빈도는 초록에 없다.", "units": [ "U-AutoimmuneThyCa24" ] }, { "claim": "수술받은 유두암 환자 9,210명의 단일 기관 자료에서 갑상선염이 함께 있던 환자는 큰 종양, 갑상선 밖 침범, 원격전이가 적었고 암 관련 사망도 적었다. 갑상선염은 수술 조직에서 확인했으므로 암보다 먼저 있었는지는 알 수 없고, 사망 추정은 갑상선염군의 사망 2건에 기대고 있다.", "units": [ "U-HashimotoOutcome21" ] }, { "claim": "앞선 통합 분석의 연관성도 수술 조직과 검사 대상 표본에서 나왔다. 검진이 많은 지역에서 진단은 늘었지만 사망률과의 연관은 보이지 않았다는 국내 자료는 발견 강도가 진단 수를 바꿀 수 있음을 보여 준다.", "units": [ "U-HashimotoPTC17", "U-KoreaThyScreen16" ] } ], "objection": "만성 염증이 종양 발생을 돕고, 같은 면역 반응이 종양의 진행은 억제한다는 설명도 두 관찰과 맞는다. 검사 빈도만으로 원격전이와 사망의 차이까지 설명되는지는 확인되지 않았다.", "changesMind": "갑상선염 진단 시점과 이후 갑상선 검사 횟수를 기록한 인구 기반 자료에서, 검사 강도를 맞춘 뒤에도 발생 차이가 남거나 같은 병기 안에서 사망 차이가 남으면 해당 방향의 판단을 다시 쓴다.", "next": [ "두 연구 원문에서 갑상선 검사 빈도와 진단 경로를 확인한다", "갑상선염 진단 뒤 암 진단까지의 기간별 위험을 보고한 자료를 찾는다" ], "holdStatus": "held" }, { "id": "QP-54", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-HTYoungFollowup26", "U-JATNodules08", "U-AITCytology14", "U-HTMR24", "U-TSHHTMR25", "U-HTTaiwanCohort13" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "암으로 가지 않는 조건은 아직 정해지지 않음", "question": "하시모토 갑상선염 환자에서 어떤 조건이면 갑상선암으로 이어지지 않는다고 말할 수 있는가?", "judgment": "그런 조건을 확정하지 않는다. 기록할 수 있는 것은 세 가지다. 추적된 환자 대부분에서는 암이 진단되지 않았다. 암은 결절이 생긴 환자 안에서 확인됐다. 유전 분석은 갑상선염이 암을 일으킨다는 근거를 찾지 못했다. 어느 것도 특정 환자에게 암이 생기지 않는다는 보장은 아니므로, 암을 막는 조건이라는 해석은 보류한다.", "basis": [ { "claim": "정기적으로 초음파를 받은 젊은 환자 1,050명 가운데 갑상선암은 10명에서 확인됐고, 소아·청소년 365명의 다른 자료에서는 11명이었다. 두 자료 모두 암은 결절이 발견된 환자에서 나왔다.", "units": [ "U-HTYoungFollowup26", "U-JATNodules08" ] }, { "claim": "성인의 연속 세포검사 표본에서는 갑상선염이 있는 결절과 없는 결절의 악성 의심 비율이 다르지 않았다. 수술받은 환자만 보면 차이가 나타났는데, 갑상선염군은 의심 소견 때문에 수술한 경우가 더 많았다.", "units": [ "U-AITCytology14" ] }, { "claim": "두 유전 분석은 갑상선염에서 암으로 가는 인과 근거를 찾지 못했다. 보험 자료에서는 갑상선염 진단 뒤 첫 3년에 암 진단이 몰려 있어, 진단 무렵 검사가 늘어난 영향과 구분되지 않는다.", "units": [ "U-HTMR24", "U-TSHHTMR25", "U-HTTaiwanCohort13" ] } ], "objection": "젊은 환자 자료에서 암 비율은 대조군보다 높았고 항체 수치와 상관을 보였다. 추적 기간의 중앙값이 6년에 못 미쳐 그 뒤의 발생은 알 수 없다.", "changesMind": "검사 강도를 맞춘 장기 추적에서 결절이 없거나 항체가 낮은 환자군의 암 발생이 대조군과 같다고 확인되면, 그 범위에서 조건을 기록한다. 반대로 결절이 없던 환자에서 암이 반복해 보고되면 두 번째 관찰을 고친다.", "next": [ "추적 자료 원문에서 결절 유무별 암 발생과 추적 기간을 확인한다", "대조군의 초음파 검사 방식이 환자군과 같았는지 확인한다" ], "holdStatus": "held" }, { "id": "QP-55", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-TSHThyCaMeta12", "U-HTTSHLT411", "U-TSHHTMR25", "U-AITChildNodule22", "U-JATNodules08" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "호르몬 수치 조절과 종양 예방은 다른 문제", "question": "갑상선 자극 호르몬 수치가 낮을수록 갑상선암 진단이 적었다는 관찰을, 호르몬 치료로 암을 예방할 수 있다는 근거로 볼 수 있는가?", "judgment": "예방 근거로 보지 않는다. 자극 호르몬이 높을수록 암 진단이 많았다는 연관성과, 치료받아 수치가 낮은 환자에서는 갑상선염군과 다른 군의 차이가 보이지 않았다는 관찰을 기록한다. 호르몬 치료가 암 발생을 줄인다는 판단은, 여기 모은 자료 가운데 그 효과를 직접 시험한 것이 없어 보류한다.", "basis": [ { "claim": "28개 연구를 합친 분석에서 자극 호르몬 수치와 갑상선암 진단은 양의 연관을 보였다. 자가면역을 함께 고려한 연구에서는 연관이 가장 약했다.", "units": [ "U-TSHThyCaMeta12" ] }, { "claim": "세포검사 표본에서 치료받지 않은 결절성 갑상선염 환자는 유두암 비율과 자극 호르몬 수치가 모두 높았다. 치료 중이면서 수치가 중앙값보다 낮은 환자에서는 군 사이 차이가 없었다. 치료 여부는 무작위로 정해지지 않았다.", "units": [ "U-HTTSHLT411" ] }, { "claim": "유전 분석은 높은 자극 호르몬과 암 위험의 연관을 보고했지만 효과 크기를 초록에 싣지 않았다. 결절이 있는 소아 표본에서는 자극 호르몬 수치가 암과 연관되지 않았고, 소아 자료에서는 치료 중에 자란 결절이 암과 연관됐다.", "units": [ "U-TSHHTMR25", "U-AITChildNodule22", "U-JATNodules08" ] } ], "objection": "자극 호르몬은 갑상선 세포의 성장 인자이므로 수치를 낮추면 종양 성장이 억제된다는 설명에는 생물학적 근거가 있고, 유전 분석도 같은 방향을 가리킨다.", "changesMind": "호르몬 치료 여부를 무작위로 나누거나 치료 시작 시점과 검사 강도를 맞춘 추적 연구에서 암 발생 차이가 확인되면 다시 판단한다.", "next": [ "치료군과 비치료군의 기저 특성과 치료 사유를 원문에서 확인한다", "자극 호르몬을 측정한 시점이 암 진단 전인지 확인한다" ], "holdStatus": "held" }, { "id": "QP-56", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-AITChildNodule22", "U-HTYoungFollowup26", "U-JATNodules08", "U-AITCytology14" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "어린 환자의 결절은 성인 자료로 못 읽음", "question": "성인 세포검사 표본에서 갑상선염과 악성 소견의 연관이 없었다는 결과를 소아·청소년 갑상선염 환자의 결절에도 적용할 수 있는가?", "judgment": "적용하지 않는다. 결절이 있어 검사받은 소아 표본에서는 갑상선염이 암과 독립적으로 연관됐다. 이 결과는 이미 결절이 있는 아이들의 것이므로, 갑상선염이 있는 아이 전체의 암 발생 위험으로 넓히는 해석은 보류한다.", "basis": [ { "claim": "1센티미터 이상 결절로 세포검사를 받은 19세 미만 환자에서 갑상선염은 암과 독립적으로 연관됐다. 갑상선염이 있다고 암이 더 퍼진 상태로 발견되지는 않았다.", "units": [ "U-AITChildNodule22" ] }, { "claim": "갑상선염 환자 전체를 추적한 두 자료에서 암이 확인된 비율은 훨씬 낮았다. 분모가 결절 환자인지 갑상선염 환자 전체인지에 따라 숫자의 뜻이 달라진다.", "units": [ "U-HTYoungFollowup26", "U-JATNodules08" ] }, { "claim": "연관이 없었던 성인 표본은 평균 나이가 58세 안팎이었다.", "units": [ "U-AITCytology14" ] } ], "objection": "소아 표본은 전문 기관에 의뢰된 환자여서 암 비율 자체가 높았다. 종양에 대한 면역 반응이 갑상선염처럼 보였을 가능성도 있다.", "changesMind": "갑상선염 진단 시점부터 결절 발생과 암 진단을 차례로 기록한 소아 전향 자료가 나오면 결절 환자와 전체 환자의 위험을 나누어 다시 쓴다.", "next": [ "소아 표본에서 갑상선염 판정 시점과 결절 발견 시점의 순서를 확인한다", "추적 자료의 암 환자 병기와 치료 뒤 경과를 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-57", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-ATAPeds15", "U-HTYoungFollowup26", "U-JATNodules08", "U-KoreaThyScreen16", "U-HTDTCMortalityKR24", "U-HTPTCReview13" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "증상 없는 환자의 정기 초음파 이득은 미확인", "question": "진찰에서 이상이 없는 하시모토 갑상선염 환자에게 초음파를 정기적으로 하면 갑상선암으로 인한 나쁜 결과가 줄어든다고 볼 수 있는가?", "judgment": "그렇게 판단하지 않는다. 정기 초음파가 결절과 작은 암을 더 많이 찾아낸다는 사실만 기록한다. 그렇게 찾아낸 암 가운데 얼마가 실제로 문제가 됐을지, 일찍 찾아서 결과가 나아지는지는 보류한다. 소아 지침이 초음파 평가를 진찰 소견과 연결해 적고 있다는 점도 함께 기록한다.", "basis": [ { "claim": "미국 소아 지침은 갑상선염 환아 자료가 제한적이라고 밝히고, 인용한 보고의 유두암 11건 중 7건이 초음파로만 발견됐으며 그중 얼마가 임상적으로 중요해졌을지는 불분명하다고 적었다. 초음파 전문가의 평가는 결절이 의심되거나 갑상선이 뚜렷하게 비대칭일 때로 연결했다.", "units": [ "U-ATAPeds15", "U-JATNodules08" ] }, { "claim": "정기 초음파를 한 젊은 환자 자료에서는 결절이 많이 발견됐고 암은 그 일부에서 확인됐다. 국내 지역 자료에서는 검진이 많을수록 진단이 늘었지만 사망률과의 연관은 보이지 않았다.", "units": [ "U-HTYoungFollowup26", "U-KoreaThyScreen16" ] }, { "claim": "갑상선염이 함께 있던 갑상선암 환자는 15년 추적에서 사망 위험이 낮았다. 세포검사 연구와 수술 표본 연구는 암 비율이 크게 달라, 어떤 환자를 검사했는지가 숫자를 좌우했다.", "units": [ "U-HTDTCMortalityKR24", "U-HTPTCReview13" ] } ], "objection": "결절이 있는 소아에서는 암 비율이 성인보다 높고 림프절 전이가 흔하므로, 일찍 찾는 쪽의 이득이 성인보다 클 수 있다. 지침은 2014년까지의 근거로 쓰였다.", "changesMind": "진찰이 정상인 갑상선염 환자를 정기 초음파군과 진찰 중심 추적군으로 나누어 병기, 치료 범위, 재발을 비교한 자료가 나오면 다시 판단한다.", "next": [ "유럽 소아 지침과 이후 개정 지침이 갑상선염 환아의 초음파 간격을 어떻게 적는지 확인한다", "초음파로만 발견된 암의 병기와 치료 뒤 경과를 추적 자료 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-58", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-HTYoungFollowup26", "U-JATNodules08", "U-HTChildKR21", "U-HTChildTR21", "U-HTChildKR18", "U-BenignThyDK18" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "추적 자료의 서로 다른 발생 비율은 합치지 않음", "question": "소아·청소년 갑상선염 추적 자료마다 갑상선암이 확인된 비율이 1%에서 8%까지 다른데, 이를 하나의 위험 수치로 묶을 수 있는가?", "judgment": "묶지 않는다. 자료마다 어떤 환자를 모았고 초음파를 얼마나 했는지가 달라 비율이 달라졌다고 기록한다. 다섯 자료 모두에서 암은 결절이 발견된 환자 안에서 확인됐다는 점은 함께 적는다. 갑상선염 환아 한 사람의 위험을 나타내는 단일 수치는 보류한다.", "basis": [ { "claim": "여러 기관이 정기 추적한 1,050명 자료에서는 암이 1%에 못 미쳤고, 한 기관이 초음파 검사 대상으로 모은 89명 자료에서는 8%에 가까웠다. 나머지 세 자료는 그 사이였다.", "units": [ "U-HTYoungFollowup26", "U-HTChildKR18", "U-JATNodules08", "U-HTChildKR21", "U-HTChildTR21" ] }, { "claim": "다섯 자료 모두 암은 결절이 있는 환자에서 진단됐고 조직형은 유두암이었다. 국내 한 자료에서는 암 환자 9명 모두 추적 중앙값 3.4년 동안 병의 증거가 없었다.", "units": [ "U-HTYoungFollowup26", "U-JATNodules08", "U-HTChildKR21", "U-HTChildTR21", "U-HTChildKR18" ] }, { "claim": "덴마크 전국 등록 자료는 갑상선 질환 진단 뒤 초기에 갑상선암 표준화 발생비가 더 높았다고 보고했다. 진단 직후의 검사 증가가 숫자에 섞인다는 뜻이다.", "units": [ "U-BenignThyDK18" ] } ], "objection": "모집 방식이 달라도 다섯 자료 모두 일반 소아에서 기대되는 것보다 높은 비율을 보였으므로, 위험이 높다는 방향 자체는 일관된다는 견해가 있다.", "changesMind": "같은 기준으로 모은 갑상선염 환아와 대조군을 같은 간격의 초음파로 추적한 자료가 나오면 그 수치를 기준으로 다시 쓴다.", "next": [ "각 자료의 모집 경로와 초음파 시행 기준을 원문에서 확인한다", "덴마크 자료 원문에서 갑상선염의 기간별 표준화 발생비를 확인한다" ], "holdStatus": "held" }, { "id": "QP-59", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-OPRA", "U-DOSTrectal", "U-NEO" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "직장암 수술 보류의 안전성은 무작위 비교가 없다", "question": "직장암에서 선행 치료 뒤 임상 반응이 좋은 환자의 수술을 미루는 전략이 곧바로 수술하는 전략만큼 안전하다고 볼 수 있는가?", "judgment": "아직 그렇게 보지 않는다. 절반가량에서 직장을 보존했고 무병 생존이 과거 성적과 비슷했다는 관찰은 기록한다. 그러나 비교 대상이 과거 자료이고 즉시 수술군과의 무작위 비교가 없어, 두 전략의 안전성이 같다는 판단은 보류한다.", "basis": [ { "claim": "OPRA는 두 치료 순서를 무작위로 나눴지만 경과 관찰과 즉시 수술을 무작위로 나누지는 않았다. 5년 무병 생존은 71%와 69%였고 과거 성적과 비슷한 범위였다.", "units": [ "U-OPRA" ] }, { "claim": "종양이 다시 자란 81명 가운데 94%가 2년 안에 확인됐다. 다시 자란 뒤 수술한 환자와 재평가 뒤 바로 수술한 환자의 무병 생존은 모두 64%로 보고됐다.", "units": [ "U-OPRA" ] }, { "claim": "면역항암 뒤 임상적 완전반응으로 수술을 하지 않은 직장암 자료와 혈액 검사를 곁들인 국소 절제 자료는 대상과 판정 방법이 달라 같은 근거로 합치지 않는다.", "units": [ "U-DOSTrectal", "U-NEO" ] } ], "objection": "다시 자란 종양을 수술로 치료한 뒤의 성적이 처음부터 수술한 환자와 같았으므로, 무작위 비교가 없어도 손해가 크지 않다고 해석할 수 있다.", "changesMind": "경과 관찰과 즉시 수술을 무작위로 비교한 시험의 장기 생존과 원격 전이 결과가 공개되면 다시 판단한다.", "next": [ "임상 반응 등급별 직장 보존과 생존을 다룬 2차 분석을 원문에서 확인한다", "경과 관찰 중 원격 전이 발생이 수술군과 다른지 보고한 자료를 찾는다" ], "holdStatus": "held" }, { "id": "QP-60", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-PHERGain", "U-APT", "U-ATEMPT" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "영상 반응으로 항암을 줄인 전략의 3년 성적", "question": "HER2 양성 조기 유방암에서 영상 반응과 수술 뒤 병리 결과에 따라 항암을 줄인 전략의 3년 성적을 항암 생략의 안전성 근거로 볼 수 있는가?", "judgment": "전략 전체의 3년 성적이 사전에 정한 기준을 넘었다는 사실만 기록한다. 항암을 실제로 생략한 환자는 약 3분의 1이고 표준 항암군과 비교하도록 설계되지 않았으므로, 항암 생략이 표준치료와 같은 결과를 낸다는 판단은 보류한다.", "basis": [ { "claim": "전략군 285명 중 227명이 영상 반응군이었고 그중 86명(37.9%)이 항암 없이 병리학적 완전반응에 이르렀다. 완전반응에 이르지 못한 반응군은 수술 뒤 항암을 받았다.", "units": [ "U-PHERGain" ] }, { "claim": "전략군의 3년 침습 무병 생존은 94.8%로 사전 기준을 충족했다. 두 군은 서로 비교하도록 설계되지 않았다.", "units": [ "U-PHERGain" ] }, { "claim": "작은 종양에서 항암 강도를 낮춘 다른 시험들은 대상과 약제가 달라 이 결과와 합치지 않는다.", "units": [ "U-APT", "U-ATEMPT" ] } ], "objection": "3년 침습 무병 생존이 95%에 가깝고 중대한 이상반응이 절반 수준이었으므로, 비교군이 없어도 일부 환자의 항암 생략을 지지하기에 충분하다는 견해가 있다.", "changesMind": "병리 반응에 따라 항암을 생략하는 전략을 표준 항암과 무작위로 비교한 결과가 나오거나, 이 시험의 5년 이상 추적에서 호르몬 수용체 양성 환자의 늦은 재발 자료가 나오면 다시 판단한다.", "next": [ "항암을 생략한 환자만의 재발 수와 호르몬 수용체 상태별 결과를 원문에서 확인한다", "같은 질문을 다루는 진행 중 무작위 시험의 등록 정보를 확인한다" ], "holdStatus": "held" }, { "id": "QP-61", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-APHINITY", "U-KATHERINE" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "보조 퍼투주맙의 생존 이득은 아직 확정 전", "question": "HER2 양성 조기 유방암의 보조요법에 퍼투주맙을 더한 이득을 림프절 상태와 무관하게 인정할 수 있는가?", "judgment": "인정하지 않는다. 전체 대상에서 침습 무병 생존이 개선됐다는 결과와 림프절 양성 환자에서 차이가 컸다는 관찰을 기록한다. 림프절 음성 환자의 이득과 전체 생존 이득은 보류한다.", "basis": [ { "claim": "1차 분석의 위험비는 0.81이었고 3년 침습 무병 생존은 94.1% 대 93.2%였다.", "units": [ "U-APHINITY" ] }, { "claim": "림프절 양성군의 8년 침습 무병 생존은 86.1% 대 81.2%였고, 림프절 음성군은 위약군만으로 93.3%였다. 세 번째 중간 분석까지 전체 생존 차이는 유의 기준에 이르지 못했다.", "units": [ "U-APHINITY" ] }, { "claim": "수술 전 치료 뒤 잔존암이 남은 환자의 보조요법은 별도 시험이 다룬 다른 질문이다.", "units": [ "U-KATHERINE" ] } ], "objection": "림프절 양성군의 결과는 추적이 길어져도 차이가 유지됐으므로, 이 환자군에서는 이득을 확정된 것으로 봐도 된다는 견해가 있다.", "changesMind": "최종 전체 생존 분석이 공개되거나 림프절 음성 환자에서 재발 감소를 보인 독립 자료가 나오면 다시 판단한다.", "next": [ "호르몬 수용체와 HER2 발현 정도에 따른 하위 분석을 확인한다", "심장 관련 이상반응의 장기 추적 보고를 확인한다" ], "holdStatus": "held" }, { "id": "QP-62", "program": "gxb", "targets": [ "ERBB2" ], "biomarkers": [ "BM-COAMP" ], "units": [ "U-A1", "U-Janjigian18", "U-CCNE1TDXd24", "U-CCNE1Rustgi24", "U-HER2GCKwon23" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "같은 검사법에서도 위암 공동증폭이 더 잦았다", "question": "위암과 유방암을 같은 검사법으로 측정해도 ERBB2 증폭 종양의 공동증폭이 위암에서 더 흔한가, 그리고 이것이 치료 내성을 설명하는가?", "judgment": "더 흔했다는 관찰은 받아들인다. 한 검사실의 같은 패널로 측정한 자료에서 위암 65명 중 25명, 유방암 53명 중 6명이었고 사전에 정한 기준을 충족했다. 다만 위암의 차이는 대부분 CCNE1에서 나왔고, CCNE1 증폭과 치료 결과의 연관을 보고한 관찰 자료는 방향이 엇갈리며 치료를 받지 않은 비교군이 없다. 공동증폭이 표적치료 내성의 원인이라는 판단은 보류한다.", "basis": [ { "claim": "자체 분석 A1에서는 위암 46.6% 대 유방암 7.3%였다. 측정법이 암종마다 달랐던 첫 외부 평가는 같은 방향을 지지했고, 다른 위암 자료를 쓴 평가는 판단 불가였다.", "units": [ "U-A1" ] }, { "claim": "중국 범암종 자료를 쓴 외부 평가(CV-A1-OM)는 두 암종을 같은 패널로 측정해 측정법 차이를 없앴다. 차이는 27.1%포인트, 95% 구간은 11.5에서 40.7이었다. 이 결과는 근거 단위가 아니라 코호트 평가 기록으로 보관한다.", "units": [ "U-A1" ] }, { "claim": "CCNE1 증폭과 HER2 표적치료 결과를 비교한 자료는 방향이 갈린다. 일본 전국 자료에서는 트라스투주맙 데룩스테칸 뒤 무진행 생존이 더 짧았고(위험비 1.90), 미국 검사실 자료와 국내 한 기관의 50명 자료도 생존이 나빴다고 보고했다. 반면 국내 다른 기관 자료에서는 CCNE1 증폭이 더 긴 무진행 생존과 연관됐다.", "units": [ "U-CCNE1TDXd24", "U-CCNE1Rustgi24", "U-CCNE1Lee15", "U-HER2GCKwon23" ] }, { "claim": "이 자료들에는 HER2 표적치료를 받지 않은 비교군이 없어, CCNE1이 치료 효과를 줄이는지 원래 경과가 나쁜 종양의 표지인지 가르지 못한다. 유방암 세포 실험은 원인 관계를 시사했지만 조기 유방암 202명 자료에서는 재발과 연관이 없었다.", "units": [ "U-CyclinEScaltriti11", "U-CyclinELuhtala16" ] }, { "claim": "한 식도위암 코호트에서는 수용체·RAS·PI3K 경로의 동반 변화가 트라스투주맙 내성과 연관됐고, 무작위 시험의 사후 분석에서는 HER2 복제수만 독립적으로 생존과 연관됐다. 두 분석의 내성 패널에는 CCNE1이 들어 있지 않다.", "units": [ "U-Janjigian18", "U-AMNESIA18", "U-JACOB" ] } ], "objection": "세 외부 자료 가운데 둘에서 같은 방향이 확인됐고 그중 하나는 측정법을 통일했으므로, 암종 차이는 사실로 받아들이고 곧바로 내성 연구로 넘어가도 된다는 견해가 있다.", "changesMind": "무작위 시험의 치료군과 대조군 양쪽에서 CCNE1 공동증폭 여부에 따른 반응과 생존을 사전에 정한 방법으로 비교한 자료가 나오면 내성과의 관계를 다시 판단한다. 같은 검사법을 쓴 다른 코호트에서 방향이 뒤집히면 암종 차이 판단도 다시 본다.", "next": [ "무작위 시험 검체에서 CCNE1 상태별 치료 효과를 본 분석이 있는지 찾는다", "치료 반응 기록이 함께 있는 위암 유전체 자료의 접근 조건을 확인한다" ], "holdStatus": "held" }, { "id": "QP-63", "program": "colorectal", "targets": [], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-FOxTROT", "U-NICHE2" ], "asOf": "2026-10-06", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-06", "title": "dMMR 결장암은 수술 전 항암 효과가 작게 보고됨", "question": "수술 전 항암이 결장암의 잔존·재발을 줄였다는 결과를 dMMR 결장암에도 그대로 적용할 수 있는가?", "judgment": "적용하지 않는다. 전체 대상에서 2년 안의 잔존·재발이 줄었다는 결과는 기록하되, dMMR 종양에서는 이득이 작았다는 하위 관찰이 있어 이 집단의 수술 전 항암 이득은 보류한다. 같은 집단의 수술 전 면역항암 자료는 대조군이 없는 별도 근거로 둔다.", "basis": [ { "claim": "FOxTROT에서 2년 안의 잔존·재발은 16.9% 대 21.5%였다. 초록은 dMMR 종양에서 이득이 거의 없었다고 적었지만 그 수치는 싣지 않았다.", "units": [ "U-FOxTROT" ] }, { "claim": "dMMR 결장암의 수술 전 면역항암 시험에서는 111명 중 75명(68%)이 병리학적 완전반응을 보였으나 대조군이 없었다.", "units": [ "U-NICHE2" ] }, { "claim": "두 시험은 대상 선정과 평가변수가 달라 수술 전 항암과 수술 전 면역항암을 직접 비교한 근거가 아니다.", "units": [ "U-FOxTROT", "U-NICHE2" ] } ], "objection": "하위 관찰이라도 생물학적으로 설명되는 방향이고 면역항암의 병리 반응이 매우 높으므로, dMMR 결장암에서는 수술 전 항암을 건너뛰는 쪽으로 이미 기울었다는 견해가 있다.", "changesMind": "dMMR 결장암에서 수술 전 면역항암과 표준치료를 무작위로 비교한 시험의 무재발 생존이 공개되거나, FOxTROT 원문의 dMMR 하위군 수치와 교호작용 검정이 확인되면 다시 판단한다.", "next": [ "FOxTROT 원문에서 dMMR 하위군의 환자 수와 사건 수를 확인한다", "dMMR 결장암 수술 전 면역항암의 무작위 시험 등록 정보를 확인한다" ], "holdStatus": "held" }, { "id": "QP-64", "program": "breast", "targets": [ "PDCD1" ], "biomarkers": [ "BM-HR" ], "units": [ "U-KN756", "U-CM7FL", "U-KN522" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-07", "title": "호르몬 양성 조기 유방암의 면역치료는 병리 결과뿐", "question": "호르몬 수용체 양성 조기 유방암에서 수술 전 항암에 면역항암제를 더해 병리학적 완전반응이 늘었다는 결과를 재발 감소의 근거로 볼 수 있는가?", "judgment": "아직 보지 않는다. 두 무작위 시험에서 병리학적 완전반응이 늘었다는 사실만 기록한다. 재발과 생존 결과는 공개되지 않았고 한 시험에서는 약물 관련 사망이 있었으므로, 이 아형에서 재발을 줄인다는 판단은 보류한다.", "basis": [ { "claim": "병리학적 완전반응은 한 시험에서 24.3% 대 15.6%, 다른 시험에서 24.5% 대 13.8%였다. 두 시험 모두 무사건 생존 결과는 아직 보고하지 않았다.", "units": [ "U-KN756", "U-CM7FL" ] }, { "claim": "니볼루맙 시험에서는 시험약 독성과 관련된 사망이 2건 있었고 위약군에는 사망이 없었다.", "units": [ "U-CM7FL" ] }, { "claim": "삼중음성 유방암에서는 같은 방식의 치료가 병리 반응에 이어 무사건 생존과 전체 생존까지 개선했다. 이것은 다른 아형의 결과다.", "units": [ "U-KN522" ] } ], "objection": "서로 다른 두 약으로 한 두 시험이 같은 크기의 반응 증가를 보였으므로 우연이 아니며, 삼중음성에서처럼 생존 이득으로 이어질 가능성이 높다는 견해가 있다.", "changesMind": "두 시험 가운데 하나라도 무사건 생존 결과를 공개하면 그 결과로 다시 판단한다. 이 아형에서 병리학적 완전반응과 장기 결과의 연관을 시험 수준에서 확인한 분석이 나와도 다시 본다.", "next": [ "두 시험의 무사건 생존 공개 일정을 등록 정보에서 확인한다", "면역 표지 양성 하위군의 정의가 두 시험에서 같은지 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-65", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-KRISTINE", "U-PHERGain" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-07", "title": "화학요법을 뺀 두 방식은 결과가 서로 달랐다", "question": "HER2 양성 조기 유방암에서 기존 화학요법을 빼는 방식들을 하나의 근거로 묶어 판단할 수 있는가?", "judgment": "묶지 않는다. 모든 환자에게서 화학요법을 다른 약으로 바꾼 시험은 병리 반응이 낮고 수술 전 진행이 더 많았다. 치료 초기 반응을 보고 일부 환자만 화학요법을 생략한 시험은 사전에 정한 3년 기준을 충족했다. 누구에게서 생략이 가능한지 가려내는 방법은 보류한다.", "basis": [ { "claim": "모든 환자에게 화학요법 대신 항체약물접합체를 쓴 시험에서 병리학적 완전반응은 44.4% 대 55.7%였고, 수술 전 국소 진행은 15건 대 0건이었다.", "units": [ "U-KRISTINE" ] }, { "claim": "영상 반응과 병리 결과에 따라 약 3분의 1만 화학요법을 생략한 시험에서는 전략군의 3년 침습 무병 생존이 94.8%였다. 이 시험은 표준 치료군과 비교하도록 설계되지 않았다.", "units": [ "U-PHERGain" ] }, { "claim": "앞 시험에서 병리학적 완전반응에 이른 환자는 치료군과 무관하게 침습 사건 위험이 낮았다. 이것은 예후 연관이며 반응에 따라 치료를 바꾸는 전략을 시험한 것은 아니다.", "units": [ "U-KRISTINE" ] } ], "objection": "두 시험의 차이는 환자를 고르는 단계가 있었느냐에서 나왔으므로, 반응에 따라 고르는 방식은 이미 충분히 뒷받침됐다는 견해가 있다.", "changesMind": "반응에 따라 화학요법을 생략하는 전략을 표준 치료와 무작위로 비교한 결과가 공개되면 다시 판단한다.", "next": [ "반응에 따라 화학요법을 줄이는 진행 중 무작위 시험의 등록 정보를 확인한다", "앞 시험에서 수술 전 진행한 환자의 특징을 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-66", "program": "gastric", "targets": [ "ERBB2", "PDCD1" ], "biomarkers": [ "BM-HER2-G", "BM-PDL1-CPS" ], "units": [ "U-PETRARCA", "U-DANTE", "U-KN585", "U-MATTERHORN" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-07", "title": "위암 병리 반응 상승과 재발 감소는 따로 본다", "question": "위암의 수술 전후 치료에 표적치료제나 면역항암제를 더해 병리 반응이 좋아졌다는 결과를 재발·생존 개선으로 읽을 수 있는가?", "judgment": "읽지 않는다. 병리 반응이 좋아진 네 시험 가운데 무사건 생존과 전체 생존까지 개선을 보인 것은 하나다. 병리 반응만 보고된 치료는 생존 결과가 나올 때까지 효과 판단을 보류한다.", "basis": [ { "claim": "HER2 이중 항체를 더한 시험은 병리학적 완전반응이 12%에서 35%로 올랐지만 81명에서 조기 종료됐고 생존 차이는 유의하지 않았다.", "units": [ "U-PETRARCA" ] }, { "claim": "아테졸리주맙을 더한 시험의 중간 보고는 병리 관해 24% 대 15%이며 생존 결과는 아직 없다.", "units": [ "U-DANTE" ] }, { "claim": "펨브롤리주맙 시험은 병리학적 완전반응이 높았지만 무사건 생존이 사전 기준을 넘지 못했다. 더발루맙 시험은 무사건 생존과 전체 생존에서 기준을 충족했다.", "units": [ "U-KN585", "U-MATTERHORN" ] } ], "objection": "같은 계열 약의 한 시험이 생존 이득을 보였으므로 병리 반응 상승은 대체로 생존 이득을 예고하며, 기준을 넘지 못한 시험은 검정력 문제였다는 견해가 있다.", "changesMind": "병리 반응만 보고된 시험들의 무사건 생존 결과가 공개되거나, 위암에서 병리 반응과 생존의 연관을 시험 수준에서 확인한 통합 분석이 나오면 다시 판단한다.", "next": [ "아테졸리주맙 시험의 생존 결과 공개 여부를 확인한다", "두 면역항암 시험의 대상과 항암 요법 차이를 원문에서 비교한다" ], "holdStatus": "held" }, { "id": "QP-67", "program": "breast", "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "units": [ "U-A2", "U-A5" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-07", "title": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "question": "전이 조직에서 ESR1 변이가 더 흔하다는 자체 분석 결과가 다른 환자 4,132명에서 다시 나타났다면 외부에서 재현됐다고 볼 수 있는가?", "judgment": "외부 재현으로 보지 않는다. 같은 병원의 다른 환자에서 같은 방향이 확인됐다는 사실만 받아들인다(전이 검체 11.8% 대 원발 검체 1.2%). 다른 기관 자료로 한 두 평가는 모두 판단 불가였으므로, 기관과 검사법이 달라도 성립한다는 판단은 보류한다.", "basis": [ { "claim": "자체 분석 A2는 2018년 자료의 호르몬 수용체 양성·HER2 음성 표본에서 전이 19.2% 대 원발 2.6%를 보고했고, 같은 환자의 짝 검체를 본 A5도 같은 방향이었다.", "units": [ "U-A2", "U-A5" ] }, { "claim": "같은 병원의 2025·2026년 자료에서 기존 자료의 환자를 환자번호로 뺀 4,132명을 평가한 결과(CV-A2-MSK)는 전이 278/2,352 대 원발 22/1,780이었다. 기관·검사법·판정 과정이 A2와 같아 코호트 평가 기록에 외부 코호트가 아니라고 표시했다.", "units": [ "U-A2" ] }, { "claim": "다른 기관 자료를 쓴 두 평가(CV-A2, CV-A5)는 표본과 검출 사건이 적어 판단 불가였다. 이 평가들은 근거 단위가 아니라 코호트 평가 기록으로 보관한다.", "units": [ "U-A2", "U-A5" ] } ], "objection": "내분비 치료 뒤 ESR1 변이가 늘어난다는 것은 여러 임상시험과 문헌에서 이미 확립된 사실이므로, 외부 재현 여부를 따로 보류할 필요가 없다는 견해가 있다.", "changesMind": "다른 기관의 충분히 큰 자료에서 사전에 정한 같은 비교가 지지되면 보류를 푼다. 수용체 아형과 치료 이력이 있는 자료에서 비교하면 A2의 원래 대상과도 맞춰 볼 수 있다.", "next": [ "다른 기관의 유방암 자료 가운데 원발·전이 검체가 충분한 것을 찾는다", "수용체 아형이 기록된 자료에서 같은 비교를 계획할 수 있는지 검토한다" ], "holdStatus": "held" }, { "id": "QP-68", "program": "gastric", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-CM577", "U-ATT5", "U-VESTIGE" ], "asOf": "2026-11-07", "status": "판단 기록됨", "updated": "2026-11-07", "updatedBy": "Claude Opus 5.5", "by": "Claude", "added": "2026-10-07", "title": "식도 접합부 보조 면역치료는 위암 근거가 아니다", "question": "식도암·위식도접합부암에서 수술 뒤 니볼루맙이 무병 생존을 늘렸다는 결과를 위암의 수술 뒤 치료에 적용할 수 있는가?", "judgment": "적용하지 않는다. 대상과 앞선 치료가 다르고, 위암에서 같은 약을 수술 뒤 항암에 더한 시험은 무재발 생존을 개선하지 못했다. 수술 전 항암 뒤 잔존암이 있는 위암·접합부암에서 수술 뒤 항암을 면역항암제 병용으로 바꾼 무작위 시험은 오히려 항암 쪽이 유리했다. 위암에서 수술 뒤 항암에 면역항암제를 더해 도움이 되는 환자군이 있는지는 보류한다.", "basis": [ { "claim": "식도·접합부암 시험은 수술 전 항암방사선 치료 뒤에도 병리적으로 암이 남은 환자를 대상으로 했고, 무병 생존 중앙값은 22.4개월 대 11.0개월이었다.", "units": [ "U-CM577" ] }, { "claim": "위암·접합부암의 수술 뒤 항암에 니볼루맙을 더한 시험에서는 무재발 생존 위험비가 0.90으로 개선이 확인되지 않았다.", "units": [ "U-ATT5" ] }, { "claim": "위암·식도위접합부 선암에서 수술 전 항암과 절제 뒤 림프절 잔존암이나 절제연 양성이 남은 환자를 대상으로 한 무작위 2상 시험은 수술 뒤 니볼루맙·이필리무맙을 수술 뒤 항암과 비교했고, 무병 생존 중앙값이 11.4개월 대 20.8개월(위험비 1.55)로 항암 쪽이 유리했다. 무익성으로 등록이 조기 중단됐다.", "units": [ "U-VESTIGE" ] }, { "claim": "두 시험은 암의 부위, 수술 전 치료, 잔존암 조건, 대조군이 모두 다르다. 한쪽의 결과로 다른 쪽을 설명할 수 없다.", "units": [ "U-CM577", "U-ATT5" ] } ], "objection": "접합부암은 두 시험에 모두 들어 있고 생물학적으로 위암과 가까우므로, 수술 전 치료 뒤 암이 남은 위암 환자에게도 같은 이득을 기대할 수 있다는 견해가 있다.", "changesMind": "수술 전 치료 뒤 잔존암이 있는 위암 환자에서 수술 뒤 항암에 면역항암제를 더하는 무작위 비교 결과가 공개되면 다시 판단한다. 항암을 면역항암제로 바꾼 비교는 이미 항암 쪽이 유리했다.", "next": [ "식도·접합부암 시험의 부위별 하위 분석과 전체 생존 결과를 확인한다", "위암에서 수술 뒤 면역항암제를 비교한 진행 중 시험의 등록 정보를 확인한다" ], "holdStatus": "held" }, { "id": "QP-69", "program": "gxb", "targets": [], "biomarkers": [], "units": [ "U-ctDNAGarcia19", "U-ctDNALate22", "U-cTRAKTN", "U-ctDNAGC25", "U-ctDNAEGCpCR24" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-07", "title": "혈액 검사의 앞선 경고와 치료 이득은 별개", "question": "수술 뒤 혈액의 종양 DNA 검사가 영상보다 여러 달 먼저 재발을 알려 준다면, 그 결과에 따라 치료하는 것이 환자에게 이득이라고 볼 수 있는가?", "judgment": "아직 그렇게 보지 않는다. 유방암과 위암에서 검사 양성이 재발 위험과 강하게 연관되고 재발보다 반년에서 일 년 앞선다는 관찰은 받아들인다. 그러나 양성 결과에 따라 치료를 시작해 결과가 나아졌다는 자료는 이 라이브러리에 없고, 유일한 개입 시험에서는 검출 시점에 이미 전이가 있는 환자가 많았다. 검사에 따른 치료의 이득은 보류한다.", "basis": [ { "claim": "유방암에서 추적 중 검출은 재발과 강하게 연관됐고 임상 재발보다 중앙값 10.7개월 앞섰다. 진단 5년 뒤의 호르몬 수용체 양성 환자에서도 원격 재발 6건 모두 검사 양성이 먼저였다(중앙값 12.4개월).", "units": [ "U-ctDNAGarcia19", "U-ctDNALate22" ] }, { "claim": "위암·접합부암에서도 수술 뒤 검출은 짧은 무재발 생존과 연관됐다. 수술 전 치료에 병리학적 완전반응을 보인 환자에서도 같은 방향이었지만 양성 환자가 3명과 5명뿐이었다.", "units": [ "U-ctDNAGC25", "U-ctDNAEGCpCR24" ] }, { "claim": "검사가 놓치는 재발이 있다. 유방암 자료에서 뇌에만 생긴 전이는 6명 중 1명만 검출됐고, 재발 환자 29명 중 6명은 재발 전까지 검출되지 않았다. 양성이어도 추적 기간에 재발하지 않은 환자도 있었다.", "units": [ "U-ctDNAGarcia19", "U-ctDNALate22" ] }, { "claim": "검사 양성 때 면역항암제를 시작한 삼중음성 유방암 시험에서는 검출 시점에 72%가 이미 영상에서 전이가 확인됐고, 치료를 시작한 5명 중 지속적으로 음성이 된 환자는 없었다. 더 민감한 검사가 몇 달 더 일찍 검출한다는 후속 분석은 그 차이가 결과를 바꾸는지 보여 주지 않는다.", "units": [ "U-cTRAKTN" ] } ], "objection": "더 민감한 검사로 더 일찍 찾으면 전이가 보이기 전에 치료할 수 있으므로, 첫 개입 시험의 실패는 검사 민감도의 문제였을 뿐 전략 자체의 한계가 아니라는 견해가 있다.", "changesMind": "검사 양성 환자를 무작위로 나눠 조기 치료와 관찰을 비교한 시험이 재발이나 생존의 개선을 보이면 그 암종과 치료에 한해 판단을 바꾼다.", "next": [ "유방암과 위암에서 검사 결과에 따라 치료를 무작위 배정하는 진행 중 시험의 등록 정보를 확인한다", "검사 음성 환자에서 치료를 줄이는 전략을 다룬 자료가 있는지 따로 찾는다" ], "holdStatus": "held" }, { "id": "QP-70", "program": "breast", "targets": [ "ERBB2", "CD274" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-IM050" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-07", "title": "HER2 양성 병용의 재발 감소는 미확인", "question": "다른 유방암 아형에서 얻은 면역치료 이득을 HER2 양성 조기 유방암으로 옮길 수 있을까?", "judgment": "이 시험의 병리 반응과 최종 생존 추적은 아테졸리주맙 추가의 유의한 이득을 확인하지 못했다. 다른 아형의 성공이나 숫자로 더 높은 생존율만으로 이 공백을 메우지 않는다. 다만 넓은 구간의 비유의 결과를 동등성이나 모든 면역치료의 효과 부재로 확대하는 해석은 보류한다.", "basis": [ { "claim": "IMpassion050의 병리 완전반응은 아테졸리주맙 62.4%, 위약 62.7%였다.", "units": [ "U-IM050" ] }, { "claim": "최종 EFS 위험비는 0.90, 신뢰구간은 0.50–1.59였고, DFS 위험비 0.71의 구간도 0.38–1.32였다.", "units": [ "U-IM050" ] }, { "claim": "초기 보고의 치명적 이상사례 5건은 모두 아테졸리주맙군에 있었으며 시험치료 관련으로 판정된 것은 2건이었다. 최종 보고의 보조치료 안전성 집단과 구분해야 한다.", "units": [ "U-IM050" ] } ], "objection": "생존 결과는 이차 평가변수이며 일부 집단의 작은 이득을 배제할 만큼 정밀하지 않을 수 있다. 수치상 하위군 차이만으로 그 집단의 이득을 확정할 수도 없다.", "changesMind": "비교 가능한 HER2 양성 조기 집단에서 사전 지정한 생존 평가변수와 안전성의 이득이 충분한 사건 수를 갖춘 무작위 비교로 확인되면 범위를 갱신한다.", "next": [ "EFS 전체 배정군과 DFS 수술 후 집단의 분모를 대조한다", "초기와 최종 안전성의 기간·집단·이상사례 정의를 원문에서 확인한다", "하위군 교호작용과 다중 검정 계획을 검토한다" ], "holdStatus": "held" }, { "id": "QP-71", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "units": [ "U-CDK46TTE26" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-07", "title": "관찰 비교의 시간 조건부터 검토함", "question": "표적시험 모방에서 보정된 생존 차이를 두 약의 우열로 인정할 수 있을까?", "judgment": "관찰된 연관은 연구 후보로 받아들이되 우월성 판단은 보류한다. 처방을 다시 받은 사람을 고르는 조건과 약물 도입 시기의 차이는 시간 관련 선택을 만들 수 있다. 조건 하나를 없앤 분석과 달력 시간을 제한한 분석이 서로 다른 집단이면 두 문제를 함께 해결했다고 읽지 않는다.", "basis": [ { "claim": "전체 기간의 생존 위험비는 0.82였고, 별도로 맞춘 달력 제한 분석에서는 0.90으로 약해졌다.", "units": [ "U-CDK46TTE26" ] }, { "claim": "달력 제한 분석은 2017년부터 각 군 1924명을 비교했다.", "units": [ "U-CDK46TTE26" ] }, { "claim": "두 번째 처방 요건을 뺀 분석의 위험비는 0.86이었으나 달력 시간은 제한하지 않았다.", "units": [ "U-CDK46TTE26" ] } ], "objection": "서로 다른 보정에서도 같은 방향의 연관이 관찰돼 무작위 비교를 설계할 이유는 생긴다. 그러나 같은 방향이 남았다는 사실만으로 잔여 시간 교란이나 측정되지 않은 예후 차이가 없다고 판정하지 않는다.", "changesMind": "치료 시작점·적격성·추적·달력 시기를 동시에 맞춘 분석과 미측정 교란 검토가 확보되고 독립 자료나 직접 무작위 비교에서 재현되면 판단을 갱신한다.", "next": [ "두 번째 처방 확인 시점과 추적 시작점의 관계를 원문에서 확인한다", "달력 제한과 최초 시작자 조건을 함께 적용한 분석이 있는지 확인한다", "사망 기록·위해 기록의 결측과 의료 접근 차이를 검토한다" ], "holdStatus": "held" }, { "id": "QP-72", "program": "breast", "targets": [], "biomarkers": [ "BM-HR" ], "units": [ "U-RSNodes26", "U-RxPONDER" ], "asOf": "2026-10-07", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-07", "title": "낮은 점수의 해석은 림프절 범위에 달린다", "question": "재발 점수가 낮다는 이유로 광범위 림프절 양성 집단의 보조항암 판단을 해결할 수 있을까?", "judgment": "이 자료는 검사를 받은 선택 집단의 치료 수신과 생존 연관을 보여 준다. 낮은 점수만으로 항암 생략을 인정하지 않고, 관찰된 연관만으로 치료의 인과효과도 확정하지 않는다. 더 적은 림프절 부담에서 얻은 결과를 이 집단으로 옮기는 해석은 보류한다.", "basis": [ { "claim": "pN2-3 적격자 50,229명 중 검사를 받은 사람은 3,110명, 6%였다.", "units": [ "U-RSNodes26" ] }, { "claim": "점수 25 이하의 선택 집단에서 항암 수신의 보정 생존 위험비는 0.62, 신뢰구간은 0.48–0.81이었다.", "units": [ "U-RSNodes26" ] }, { "claim": "RxPONDER와 이번 등록 자료는 적용하는 림프절 범위와 연구 설계가 달라 같은 질문으로 합치지 않는다.", "units": [ "U-RxPONDER", "U-RSNodes26" ] } ], "objection": "보정 뒤 남는 생존 연관은 치료 생략을 당연시하지 말아야 할 이유다. 하지만 검사·항암 선택과 다른 예후 요인이 보정으로 모두 사라졌다는 근거는 아니다.", "changesMind": "같은 림프절 범위와 점수 정의에서 치료 시점을 맞춘 무작위 비교나 적절한 독립 인과 추론 자료가 재발·생존·위해를 함께 확인하면 적용 경계를 갱신한다.", "next": [ "검사 선택과 항암 선택의 기준을 원문에서 대조한다", "시작 시점·치료 결정·추적의 순서를 확인한다", "다른 NCDB 보고와 환자 중복 가능성을 검토한다" ], "holdStatus": "held" }, { "id": "QP-73", "program": "gxb", "targets": [], "biomarkers": [], "units": [ "U-GCMMA26", "U-BMPP826" ], "asOf": "2026-10-08", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-08", "title": "복구 경로가 같아도 내성 조건은 다르다", "question": "위암의 옥살리플라틴 내성과 삼중음성 유방암의 독소루비신 내성을 모두 유전물질 복구가 강화된 하나의 치료 표적으로 다룰 수 있을까?", "judgment": "복구에 연결된 실험 결과까지 받아들이되 암종·약제·복구 경로를 분리한다. 위암의 메틸말론산 실험과 유방암의 MPP8 제거 실험은 서로 다른 조건이다. 유전적 제거 또는 동물에서의 감수성 회복을 사람에게 쓸 병용 치료나 완치 근거로 옮기는 해석은 보류한다.", "basis": [ { "claim": "위암 실험에서 메틸말론산은 옥살리플라틴의 손상을 줄이고 ATM·ATR에 연결된 상동재조합 복구를 강화했다. 세포·동물 수준에서 보고된 결과이며 사람의 치료 비교가 아니다.", "units": [ "U-GCMMA26" ] }, { "claim": "삼중음성 유방암에서는 MPP8 제거가 비상동 말단 연결 복구를 늦추고 세포·이식 종양의 독소루비신 감수성을 높였다. 잘린 PARP1 증가는 세포 사멸 지표이며 억제제 감수성을 검증한 것이 아니다.", "units": [ "U-BMPP826" ] } ], "objection": "두 연구가 공통된 손상 복구 취약성을 포착했을 가능성은 있다. 다만 서로 다른 약제와 유전적 조작이 같은 선택적 치료 효과를 내는지는 현재 근거로 알 수 없다.", "changesMind": "같은 약제·노출·유전 배경을 맞춘 비교와 복구 경로의 되살림 대조, 정상 조직 위해, 독립 검증이 나오면 공통 병용 후보의 범위를 다시 정한다.", "next": [ "약제의 손상과 복구 경로별 실험 조건을 원문에서 대조한다", "유전적 제거와 약물 억제의 선택성·노출·정상 조직 위해를 구분한다", "비타민 보충 실험과 사람의 치료 비교를 분리해 추적한다" ], "holdStatus": "held" }, { "id": "QP-74", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-FANCMAdapt26" ], "asOf": "2026-10-08", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-08", "title": "같은 유전자군도 억제 방향은 갈릴 수 있다", "question": "BRCA1과 BRCA2가 결핍된 종양에서 같은 복구 단백질을 억제하면 모두 같은 방향의 치료 취약성이 생길까?", "judgment": "그렇게 묶지 않는다. 이번 세포 체계에서 FANCM은 BRCA1 결핍에는 생존 의존성으로, BRCA2 결핍에는 복제 분기 손상과 PARP 억제제 감수성을 높이는 쪽으로 보고됐다. BRCA2 결핍에서 이를 없앤 결과를 치료 이득으로 읽거나 두 유전자군에 공통 억제를 제안하는 해석은 보류한다.", "basis": [ { "claim": "등유전성 급성 결핍 실험에서 FANCM의 효과 방향이 BRCA1과 BRCA2 사이에 갈렸다. BRCA2 결핍에서 FANCM을 없애자 복제 분기의 안정성과 증식이 회복됐지만 상동재조합과 단일 가닥 틈새는 회복되지 않았다.", "units": [ "U-FANCMAdapt26" ] }, { "claim": "한 BRCA2 변이 유방암 환자의 FANCM 결합 변이는 PARP 억제제 내성과 연관돼 보고됐다. 그 관찰은 환자군 전체의 예측 검사나 인과효과 검증이 아니다.", "units": [ "U-FANCMAdapt26" ] } ], "objection": "급성 결핍 세포의 유전 배경과 실제 종양의 오랜 적응은 다를 수 있다. 관찰된 환자의 내성에는 다른 변화가 함께 작용했을 가능성도 남아 있다.", "changesMind": "서로 다른 BRCA1·BRCA2 배경에서 선택적 조작과 되살림 대조가 재현되고 환자 유래 모형 및 적절한 임상 비교로 방향이 확인되면 적용 범위를 갱신한다.", "next": [ "두 결핍 상태의 세포 배경·분기 보호·약물 노출을 원문에서 확인한다", "환자 변이의 출현 시점과 함께 생긴 내성 변화를 대조한다", "급성 결핍과 지속된 종양 결핍을 구분한 독립 검증을 찾는다" ], "holdStatus": "held" }, { "id": "QP-75", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-GDSCOxali26" ], "asOf": "2026-10-09", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-08", "title": "GDSC 예측과 치료 반응의 검증은 다르다", "question": "세포주에서 배운 약물 감수성 모형이 위암의 발현 자료를 두 집단으로 나누면 실제 옥살리플라틴 반응을 검증한 것으로 볼 수 있을까?", "judgment": "모형이 만든 집단의 생물학적 특징을 정리한 결과로 기록한다. 세포주 안의 검증, 환자 자료로 옮긴 예측, 다른 자료의 예후 연관은 각각 다른 평가다. 모형이 정의한 집단을 구분하는 성능이나 세포의 발현 변화를 사람의 치료 반응 예측 정확도로 읽는 해석은 보류한다.", "basis": [ { "claim": "GDSC2 세포주에서 배운 능선 회귀를 TCGA 위암으로 옮겨 예측 감수성의 상·하위 사분위로 집단을 만들었다. 해당 위암의 실제 약물 반응을 정답으로 삼은 검증은 보고되지 않았다.", "units": [ "U-GDSCOxali26" ] }, { "claim": "내성처럼 예측된 집단과 연결된 대사 프로그램이 다른 코호트에서는 유리하거나 중립적인 생존 연관을 보였다. 약물 감수성 추정과 예후는 같은 질문이 아니다.", "units": [ "U-GDSCOxali26" ] }, { "claim": "약물을 준 AGS 세포에서 일부 전령 RNA가 변했지만 단백질 수준의 인과 기전이나 환자 반응의 정확성을 검증한 것은 아니다.", "units": [ "U-GDSCOxali26" ] }, { "claim": "공식 전문은 범암종 세포주 미세배열 발현 자료를 플랫폼 보정 없이 환자 RNA 염기서열 기반 발현 자료로 옮겼다고 밝힌다. 같은 발현 자료에서 모형이 만든 집단을 다시 분석했으므로 독립된 약물 내성 검증이 아니다.", "units": [ "U-GDSCOxali26" ] } ], "objection": "직접 반응 자료가 부족할 때 이 전이 모형은 검증할 대사 가설을 만드는 데 도움이 될 수 있다. 그 가능성과 임상 정확도를 확인했다는 주장은 구분해야 한다.", "changesMind": "미리 고정한 모형이 독립된 옥살리플라틴 치료 코호트의 실제 반응에서 적절한 기준보다 개선되고 보정·오류·아형별 성능이 확인되면 환자 반응 예측 범위를 갱신한다.", "next": [ "전문의 자료 범위는 확인했고, 다음은 실행 코드에서 전처리·분할·모형 고정의 구현을 대조한다", "예후 평가와 약제 반응 평가에 사용된 환자 자료를 구분한다", "접근 조건을 충족한 실제 치료 반응 자료가 생기면 사전 고정한 평가를 설계한다" ], "updated": "2026-10-09", "updatedBy": "Codex (GPT-6)", "holdStatus": "held" }, { "id": "QP-76", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-TDM1Liver26" ], "asOf": "2026-10-09", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-09", "title": "누적 간 위해는 보조·전이 치료를 나눠 읽음", "question": "T-DM1을 받은 보조·전이 치료 환자의 간 위해를 합친 비율로 모든 치료 차수의 위험이나 다른 접합체의 위해를 판단할 수 있을까?", "judgment": "혼합한 관찰 코호트의 비율로 기록하고 치료 맥락·노출 기간·평가 정의를 붙인다. 보조·전이 치료 사이의 차이를 약제의 인과 위해나 개인별 위험으로 해석하는 것은 보류한다. 누적 투여량과의 연관도 노출 시간이 긴 사람에게 사건을 더 발견할 기회가 있었다는 문제를 함께 검토한다.", "basis": [ { "claim": "보조·전이 치료를 합친 후향적 코호트에서 문맥 고혈압·동모양혈관 간 손상 복합지표가 보고됐다. 영상 변화와 임상 소견 또는 생검으로 정의해 모든 사건이 같은 방식으로 확인된 것은 아니다.", "units": [ "U-TDM1Liver26" ] }, { "claim": "간 위해 관련 약제 중단과 출혈 등 중요한 합병증도 관찰됐다. 누적 용량의 연관은 노출 기간을 반영할 수 있고, 낮은 기저 혈소판의 연관은 작은 하위집단에서 나온 값이라는 저자 한계가 있다.", "units": [ "U-TDM1Liver26" ] } ], "objection": "대조군이 없어도 중요한 위해 신호를 추적할 가치는 있다. 다만 치료 선택·관찰 기간·다른 간 질환이 사건의 발견과 연관에 함께 영향을 줄 수 있다.", "changesMind": "치료 맥락과 관찰 시간을 맞춘 독립 코호트 및 적절한 대조에서 같은 사건 정의로 위해가 재현되고 시간 의존 분석과 교란 검토가 충분하면 해석 범위를 갱신한다.", "next": [ "보조·전이 치료별 추적 기간과 사건 분모를 원문에서 대조한다", "누적 용량·관찰 시간·약제 중단을 함께 다룬 분석인지 확인한다", "복합지표와 생검 확인·중요 합병증을 구분한 독립 자료를 찾는다" ], "holdStatus": "held" }, { "id": "QP-77", "program": "colorectal", "targets": [], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-MLH1Punctate26" ], "asOf": "2026-10-09", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-09", "title": "항체에 따라 점상 염색의 해석이 달라짐", "question": "대장암의 불일치 복구 검사에서 MLH1의 점상 핵 염색을 단백질이 보존됐다는 뜻으로 바로 읽을 수 있을까?", "judgment": "이 연구의 VENTANA M1 항체와 선택된 검체에서는 점상 염색을 보존으로 읽으면 오류가 생길 수 있다고 기록한다. 다른 항체로 확인한 소실 양상과 내부 대조·검체 부위를 함께 봐야 하는 방법상의 공백이다. 모든 항체의 염색, 분자적 미세부수체 상태, 개인의 유전성 질환이나 면역치료 반응으로 자동 변환하는 해석은 보류한다.", "basis": [ { "claim": "선택된 대장암 생검·절제 표본 쌍에서 M1 항체의 점상 염색을 다른 G168-15 항체로 다시 확인하자 MLH1 단백질 소실에 해당한다고 보고됐다.", "units": [ "U-MLH1Punctate26" ] }, { "claim": "표면과 깊은 부위의 양상이 다르거나 전체가 점상인 경우가 있었고, 처음 판독자의 오해도 보고됐다. 그 사례 집합이 전체 검사 성능이나 치료 결과를 측정한 것은 아니다.", "units": [ "U-MLH1Punctate26" ] } ], "objection": "검체 선택, 고정 조건, 항체 및 판독자의 경험이 결과에 영향을 줄 수 있다. 이 작은 선택 집합에서 확인한 오류를 전체 대장암 검사의 발생률로 읽을 수 없다.", "changesMind": "표준화한 내부 대조와 맹검 판독, 다른 기관·항체의 재현, 적절한 분자 검사 대조가 갖춰지면 방법의 적용 범위를 다시 정한다. 치료 이득은 별도의 임상 비교가 필요하다.", "next": [ "검체 선택과 고정·염색 조건 및 내부 대조를 원문에서 확인한다", "표면·깊은 부위와 항체별 판독 재현성을 구분한다", "단백질 소실과 분자 검사·유전성 판정·치료 결과의 연결을 따로 검토한다" ], "holdStatus": "held" }, { "id": "QP-78", "program": "breast", "targets": [], "biomarkers": [ "BM-HR" ], "units": [ "U-ERLowOmission26" ], "asOf": "2026-10-10", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-10", "title": "낮은 수용체 발현군의 생존 연관을 따져 봄", "question": "수용체 저발현 유방암의 잔존 질환군에서 내분비치료를 생략한 사람의 생존이 더 나빴다면, 치료를 시작했을 때의 인과 이득과 독립 재현까지 확인된 것일까?", "judgment": "잔존 질환을 포함한 조정 관찰 연관으로 기록한다. 이전 환자 기간을 포함한 확대 분석은 같은 자료원의 후속 보고이므로 독립 재현으로 세지 않는다. 치료 선택·시작 시점·누락과 교란을 검토하기 전에는 개인별 치료 이득이나 생략의 안전성으로 해석하는 범위를 보류한다.", "basis": [ { "claim": "항암치료를 받은 수용체 저발현 초기 유방암의 등록 자료에서 내분비치료 생략과 전체 생존의 불리한 연관이 보고됐다. 전체 등록 집합과 생존 분석 집합의 진단 기간 및 분모는 다르다.", "units": [ "U-ERLowOmission26" ] }, { "claim": "선행항암 뒤 잔존 질환군의 연관도 보고됐지만 초록에는 잔존 질환에 따른 치료 효과 차이를 직접 검정한 결과와 신뢰구간이 없다. 이전 분석과 환자 기간이 겹치므로 별도 검증군의 재현으로 바꾸지 않는다.", "units": [ "U-ERLowOmission26" ] } ], "objection": "일관된 관찰 신호는 다음 비교 질문을 정하는 데 도움이 된다. 그러나 치료를 선택하거나 지속할 수 있었던 사람의 상태·접근성·추적 조건이 생존과 함께 달랐을 가능성은 남는다.", "changesMind": "치료 시작과 추적 시작을 맞추고 누락·교란·시간 관련 오류를 검토한 자료에서 결과가 유지되며, 겹치지 않는 독립 자료 또는 적절한 전향 비교가 실제 치료 이득을 평가하면 범위를 갱신한다.", "next": [ "원문의 치료 노출·생존 추적 시작 시점과 누락 처리부터 확인한다", "앞선 등록 자료와 겹치는 진단 기간·대상자를 구분한다", "잔존 질환과 병리 완전반응 사이의 효과 차이는 상호작용 검정으로 따로 평가한다" ], "holdStatus": "held" }, { "id": "QP-79", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [], "units": [ "U-SUV39H2Splice26" ], "asOf": "2026-10-10", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-10", "title": "엑손 조절과 환자 내성 극복은 분리함", "question": "유방암 세포에서 엑손 포함과 연결된 단백질을 줄여 세포주기 억제제 감수성이 돌아왔다면, 엑손만을 조절하는 치료로 환자 내성을 극복했다고 볼 수 있을까?", "judgment": "세포에서 확인한 발현·활성 조절과 노화 상태의 회복을 검증 후보로 기록한다. 전체 단백질을 줄인 효과를 특정 엑손만의 치료 효과로 바꾸거나, 별도 환자 예후 연관을 약제 반응의 검증으로 쓰는 해석은 보류한다. 사람의 선택성·노출·위해·오래 지속되는 종양 제어는 아직 확인되지 않았다.", "basis": [ { "claim": "저자는 내성 유방암 세포의 엑손 포함 증가와 단백질 과발현을 연결하고, 안티센스 올리고뉴클레오타이드 또는 효소 억제제로 발현이나 활성을 줄여 감수성과 치료 유도 노화가 회복됐다고 보고했다.", "units": [ "U-SUV39H2Splice26" ] }, { "claim": "크로마틴과 세포주기 억제 단백질의 전사 조절을 기전으로 제시했고 환자의 불리한 예후 연관도 보고했다. 세포 상태의 변화와 별도 생존 연관은 환자의 치료 반응이나 완치 검증을 대신하지 않는다.", "units": [ "U-SUV39H2Splice26" ] } ], "objection": "엑손 포함 양상과 조절 실험이 같은 방향이면 유망한 내성 기전 후보가 될 수 있다. 다만 전체 발현 감소, 다른 효소에 대한 작용, 세포 노화와 지속 억제의 차이를 먼저 분리해야 한다.", "changesMind": "동형과 엑손에 특이적인 조작 및 되살림 대조로 기여가 구분되고, 독립 모델에서 선택성·노출·위해와 지속 제어가 확인되면 전임상 범위를 갱신한다. 환자 치료 반응은 별도의 적절한 임상 검증이 필요하다.", "next": [ "엑손 포함 변화와 전체 발현 감소를 구분한 대조를 원문에서 찾는다", "독립 내성 모델·되살림 대조·정상 조직 선택성을 확인한다", "세포 노화의 지속성과 종양 재성장 및 환자 반응을 서로 다른 평가로 둔다" ], "holdStatus": "held" }, { "id": "QP-80", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-ZETA", "U-T-EXAM", "U-T-LIBRETTO531" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "수질암 두 시험의 위험비는 나란히 못 놓음", "question": "진행성 갑상선 수질암에서 반데타닙과 카보잔티닙의 위약 대조 시험이 보고한 무진행 생존 위험비를 견주어 어느 약이 더 낫다고 말할 수 있는가?", "judgment": "말하지 않는다. 두 시험 모두 위약보다 무진행 생존이 길었다는 결과는 기록한다. 다만 한 시험은 영상으로 진행이 확인된 환자만 받았고 다른 시험은 그런 조건을 두지 않아 위약군의 경과부터 다르다. 두 약의 우열과 전체 생존 이득은 보류한다.", "basis": [ { "claim": "반데타닙 시험은 331명을 배정해 무진행 생존 위험비 0.46을 보고했다. 전체 생존 자료는 미성숙했고 위험비는 0.89였으며, 진행 뒤에는 공개 투약으로 넘어갈 수 있었다.", "units": [ "U-T-ZETA" ] }, { "claim": "카보잔티닙 시험은 영상으로 진행이 확인된 330명에서 무진행 생존 중앙값 11.2개월 대 4.0개월, 위험비 0.28을 보고했다. 용량 감량이 79%에서 있었고 초록에 전체 생존 결과는 없다.", "units": [ "U-T-EXAM" ] }, { "claim": "선택적 RET 억제제의 무작위 시험은 카보잔티닙 또는 반데타닙을 대조군으로 두고 무진행 생존 위험비 0.28을 보고했다. 이 시험은 두 대조 약을 서로 비교하지 않았다.", "units": [ "U-T-LIBRETTO531" ] } ], "objection": "카보잔티닙 시험의 위험비가 더 작고 진행이 확인된 환자에서 얻은 결과이므로, 더 불리한 환자에서도 효과가 컸다고 읽어 카보잔티닙이 낫다고 보는 견해가 있다.", "changesMind": "두 약을 같은 선정 기준으로 무작위 비교한 결과가 공개되거나, 두 시험의 최종 전체 생존과 RET 변이별 결과가 원문에서 확인되면 다시 판단한다.", "next": [ "두 시험의 최종 전체 생존 보고를 찾아 등록 정보와 대조한다", "두 시험의 선정 기준에서 진행 확인 조건을 원문으로 확인한다" ], "holdStatus": "held" }, { "id": "QP-81", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-KoreaThyScreen16" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "지켜본 저위험 유두암의 결과는 범위가 좁다", "question": "저위험 갑상선 유두암을 수술 없이 지켜본 코호트에서 진행이 드물었다는 결과를 어디까지 넓혀 읽을 수 있는가?", "judgment": "이미 저위험 암으로 진단되어 관찰을 선택한 성인에 한해 기록한다. 두 코호트에서 관찰 중 원격 전이가 보고되지 않았다는 점은 받아들인다. 암 진단이 없는 사람, 소아, 더 큰 종양, 평생의 안전성으로는 넓히지 않고 보류한다. 젊을수록 진행이 많았다는 관찰도 함께 적는다.", "basis": [ { "claim": "일본 코호트 1235명은 평균 75개월 관찰하는 동안 원격 전이나 유두암 사망이 없었다. 진행은 60세 이상에서 가장 적고 40세 미만에서 가장 많았다.", "units": [ "U-PTMCObserveAge14" ] }, { "claim": "미국 코호트 291명에서 지름이 3 mm 이상 커진 환자는 11명(3.8%)이었고 5년 누적 발생은 12.1%였다. 관찰 중앙값은 25개월이었고 국소·원격 전이는 생기지 않았다.", "units": [ "U-PTCSurveillanceUS17" ] }, { "claim": "두 코호트 모두 환자가 관찰을 선택했고 즉시 수술군과의 비교가 없다. 국내 지역 자료에서는 검진이 많은 지역일수록 진단이 많았지만 사망과의 연관은 관찰되지 않았다.", "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-KoreaThyScreen16" ] } ], "objection": "원격 전이와 사망이 한 건도 없었고 뒤늦게 수술한 환자의 경과도 좋았으므로, 저위험 유두암을 지켜보는 전략의 안전성은 이미 결론이 났다는 견해가 있다.", "changesMind": "관찰과 즉시 수술을 미리 정한 기준으로 비교한 전향 연구의 장기 결과가 공개되거나, 소아·청소년이나 갑상선염 동반 환자를 따로 추적한 관찰 자료가 나오면 범위를 다시 쓴다.", "next": [ "국내 다기관 전향 관찰 코호트의 결과 보고를 찾아 확인한다", "일본 코호트 원문에서 연령군별 진행 비율을 확인한다" ], "holdStatus": "held" }, { "id": "QP-82", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-ARROW", "U-T-LIBRETTO001", "U-T-LIBRETTO531" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "선택적 RET 억제제끼리의 우열은 비교가 없다", "question": "프랄세티닙과 셀퍼카티닙의 단일군 반응률을 나란히 놓아 어느 선택적 RET 억제제가 더 나은지 말할 수 있는가?", "judgment": "말하지 않는다. 두 약 모두 RET 변이 수질암과 RET 융합 갑상선암에서 높은 반응률이 보고됐다는 점은 기록한다. 그러나 대조군 없는 코호트의 반응률은 환자 구성과 평가 시점이 달라 서로 견줄 수 없다. 무작위 비교 근거는 이 근거 모음 안에서 셀퍼카티닙에만 있고, 두 약의 우열은 보류한다.", "basis": [ { "claim": "프랄세티닙 코호트의 반응률은 치료 경험이 없는 수질암 21명 중 15명(71%), 이전에 카보잔티닙이나 반데타닙을 쓴 55명 중 33명(60%), 융합 양성 아홉 명 중 여덟 명(89%)이었다.", "units": [ "U-T-ARROW" ] }, { "claim": "셀퍼카티닙 단일군 코호트의 반응률은 이전에 그 약들을 쓴 수질암 55명에서 69%, 쓰지 않은 88명에서 73%, 융합 양성 19명에서 79%였다.", "units": [ "U-T-LIBRETTO001" ] }, { "claim": "셀퍼카티닙은 수질암 무작위 시험에서 카보잔티닙 또는 반데타닙 대조군보다 무진행 생존이 길었다(위험비 0.28). 프랄세티닙의 무작위 비교는 이 근거 모음에 없다.", "units": [ "U-T-LIBRETTO531" ] } ], "objection": "두 약의 반응률 구간이 겹치고 작용 표적이 같으므로 효과는 사실상 같다고 보고, 독성과 접근성으로만 가르면 된다는 견해가 있다.", "changesMind": "두 약을 직접 비교한 자료나 프랄세티닙의 갑상선암 무작위 시험 결과가 공개되면 다시 판단한다.", "next": [ "프랄세티닙의 갑상선암 후속 보고에서 무진행 생존과 전체 생존을 확인한다", "두 단일군 코호트의 선정 기준과 반응 평가 시점을 원문에서 대조한다" ], "holdStatus": "held" }, { "id": "QP-83", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-CodeBreaK300", "U-KRYSTAL1CRC" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "KRAS G12C 병용 효과는 고용량에서만 확인", "question": "KRAS G12C 변이 대장암에서 KRAS 억제제와 EGFR 항체의 병용이 표준치료보다 낫다는 결과는 어느 용량과 어느 평가변수까지 확인됐는가?", "judgment": "소토라십 960 mg과 파니투무맙 병용의 무진행 생존까지만 확인된 것으로 기록한다. 학술지 정정 뒤 240 mg 용량은 유의하게 길었다고 적히지 않는다. 전체 생존 이득, 다른 KRAS 억제제 병용과의 우열, 단독요법 대비 병용의 무작위 근거는 보류한다.", "basis": [ { "claim": "정정된 수치로 무진행 생존 위험비는 960 mg군 0.48(95% 신뢰구간 0.30~0.78), 240 mg군 0.59(0.37~0.95, P=0.036)였고, 정정된 결론은 960 mg 용량만 유의하게 길었다고 적는다.", "units": [ "U-CodeBreaK300" ] }, { "claim": "같은 시험의 객관적 반응은 26.4%, 5.7%, 0%였고 전체 생존 자료는 성숙하지 않았다. 군마다 환자는 53명 또는 54명이었다.", "units": [ "U-CodeBreaK300" ] }, { "claim": "아다그라십 연구는 무작위 배정이 없는 코호트로, 반응률이 단독 19%, 세툭시맙 병용 46%였다. 두 코호트의 차이는 비교 효과가 아니다.", "units": [ "U-KRYSTAL1CRC" ] } ], "objection": "두 용량 모두 방향이 같고 240 mg군의 위험비 구간도 무효 값을 넘지 않으므로, 정정은 유의수준 문턱의 문제일 뿐 병용의 효과는 용량과 무관하게 확인됐다는 견해가 있다.", "changesMind": "이 시험의 최종 전체 생존이 공개되거나, KRAS 억제제 단독과 EGFR 항체 병용을 무작위로 비교한 결과가 나오면 다시 판단한다.", "next": [ "정정된 원문에서 반응률과 이상반응 수치가 바뀌었는지 확인한다", "이 시험의 전체 생존 후속 보고를 찾는다" ], "holdStatus": "held" }, { "id": "QP-84", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-RECOURSE", "U-FRESCO2", "U-SUNLIGHT" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "후기 치료의 생존 이득은 크기를 함께 적는다", "question": "불응성 전이성 대장암에서 전체 생존을 유의하게 늘린 후기 치료 시험들을 어떻게 기록해야 하는가?", "judgment": "유의한 생존 이득으로 기록하되 중앙값 차이와 독성을 반드시 함께 적는다. 위약 대조 두 시험에서 생존 중앙값 차이는 두세 달 안팎이었고 어느 군도 한 해에 못 미쳤다. 서로 다른 시험의 중앙값을 견주어 약의 순서를 정하는 해석과, 이 결과를 장기 생존이나 완치로 읽는 해석은 보류한다.", "basis": [ { "claim": "TAS-102 시험은 800명에서 생존 중앙값 7.1개월 대 5.3개월(위험비 0.68)을 보고했다. 호중구 감소가 38%에서 있었다.", "units": [ "U-RECOURSE" ] }, { "claim": "프루퀸티닙 시험은 691명에서 7.4개월 대 4.8개월(위험비 0.66)을 보고했다. 3등급 이상 이상반응은 63% 대 50%였다.", "units": [ "U-FRESCO2" ] }, { "claim": "TAS-102에 베바시주맙을 더한 시험은 10.8개월 대 7.5개월(위험비 0.61)을 보고했다. 이 시험은 이전 항암요법이 두 가지 이하인 환자가 대상이어서 위 두 시험과 대상이 다르다.", "units": [ "U-SUNLIGHT" ] } ], "objection": "선택지가 없는 환자에게 두세 달의 연장도 의미가 크고 세 시험의 위험비가 비슷하므로, 크기를 따로 강조하는 것은 이득을 깎아내리는 기록이라는 견해가 있다.", "changesMind": "후기 치료끼리 직접 비교한 무작위 결과나, 삶의 질과 생존을 함께 본 분석이 공개되면 순서와 크기에 대한 기록을 다시 쓴다.", "next": [ "프루퀸티닙 시험의 삶의 질 분석 보고를 확인한다", "세 시험의 이전 치료 횟수 기준을 원문에서 대조한다" ], "holdStatus": "held" }, { "id": "QP-85", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-IDEA18", "U-MOSAIC" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "보조 항암 기간 단축은 요법에 따라 갈린다", "question": "3기 결장암의 옥살리플라틴 보조 항암을 6개월에서 3개월로 줄여도 된다고 말할 수 있는가?", "judgment": "전체 대상에서는 말하지 않는다. 미리 정한 비열등성은 전체 집단에서 확인되지 않았다. CAPOX에서와 저위험군에서 차이가 작았다는 결과는 하위 분석으로 기록하고, 요법 선택이 무작위가 아니었다는 점을 함께 적는다. 요법과 위험군에 따른 기간 선택은 보류한다.", "basis": [ { "claim": "12,834명을 합친 분석에서 3개월 대 6개월의 무병 생존 위험비는 1.07(95% 신뢰구간 1.00~1.15)로, 비열등성 한계 1.12를 넘었다.", "units": [ "U-IDEA18" ] }, { "claim": "요법별 위험비는 CAPOX 0.95, FOLFOX 1.16이었다. T4 또는 N2 종양에서는 6개월이 더 나았다(3년 무병 생존 64.4% 대 62.7%).", "units": [ "U-IDEA18" ] }, { "claim": "옥살리플라틴을 더한 보조 항암의 근거가 된 시험은 장기 추적에서 생존 이득을 보고했다. 기간 단축 분석의 초록에는 전체 생존과 신경 독성 수치가 없다.", "units": [ "U-MOSAIC", "U-IDEA18" ] } ], "objection": "저위험군에서 3년 무병 생존이 83.1%와 83.3%로 사실상 같았고 신경 독성은 기간에 비례하므로, 적어도 저위험군에서는 단축이 이미 확립됐다는 견해가 있다.", "changesMind": "이 분석의 전체 생존 최종 보고와 신경 독성 수치를 원문에서 확인하거나, 요법을 무작위로 배정한 기간 비교가 공개되면 다시 판단한다.", "next": [ "같은 분석의 전체 생존 후속 보고를 찾아 확인한다", "원문에서 기간별 신경 독성 빈도를 확인한다" ], "holdStatus": "held" }, { "id": "QP-86", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-BREAKWATER", "U-BEACON" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "BRAF 변이 일차 치료의 생존은 중간 분석 단계", "question": "BRAF V600E 변이 전이성 대장암의 일차 치료에서 표적 병용과 항암의 조합이 전체 생존을 늘렸다고 확정할 수 있는가?", "judgment": "무진행 생존의 개선은 확인된 결과로 기록한다. 전체 생존은 중간 분석에서 유의했다는 단계로 적고 최종 분석 전까지 크기를 확정하지 않는다. 항암 없이 표적 병용만 쓴 군의 결과가 초록에 없으므로 항암을 더한 몫이 얼마인지는 보류한다.", "basis": [ { "claim": "일차 치료 시험에서 무진행 생존 중앙값은 12.8개월 대 7.1개월(위험비 0.53), 중간 분석의 전체 생존 중앙값은 30.3개월 대 15.1개월(위험비 0.49)이었다.", "units": [ "U-BREAKWATER" ] }, { "claim": "같은 시험에서 치료 중 중대한 이상반응은 46.1% 대 38.9%였다. 초록은 표적 병용 단독군의 결과와 군별 환자 수를 싣지 않았다.", "units": [ "U-BREAKWATER" ] }, { "claim": "이전 치료를 받은 환자의 시험에서는 표적 병용의 전체 생존 중앙값이 9.3개월, 대조군이 5.9개월이었다. 두 시험은 치료 차수가 달라 수치를 이어 붙이지 않는다.", "units": [ "U-BEACON" ] } ], "objection": "위험비가 0.49로 크고 반응률과 무진행 생존이 모두 같은 방향이므로, 중간 분석이라는 이유로 생존 이득을 유보하는 것은 지나치게 조심스럽다는 견해가 있다.", "changesMind": "전체 생존의 최종 분석과 표적 병용 단독군의 결과가 공개되면 크기와 항암의 몫을 다시 쓴다.", "next": [ "이 시험의 최종 전체 생존 보고를 감시한다", "표적 병용 단독군의 무진행 생존과 반응률을 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-87", "program": "colorectal", "targets": [ "CD274" ], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-ATOMIC", "U-NICHE2" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "dMMR 3기 보조 면역항암의 이득은 재발 지표까지", "question": "절제한 3기 dMMR 결장암에서 보조 항암에 면역항암제를 더한 이득은 어디까지 확인됐는가?", "judgment": "3년 무병 생존의 개선까지 확인된 것으로 기록한다. 전체 생존 결과는 초록에 없어 보류한다. 두 군 모두 옥살리플라틴 항암을 받았으므로 항암 없이 면역항암만 쓰는 전략이나 수술 전 면역항암과의 우열은 이 시험으로 판단하지 않는다.", "basis": [ { "claim": "355명과 357명을 배정한 시험에서 3년 무병 생존은 86.3% 대 76.2%(위험비 0.50, 95% 신뢰구간 0.35~0.73)였다.", "units": [ "U-ATOMIC" ] }, { "claim": "3등급 또는 4등급 이상반응은 84.1% 대 71.9%로 면역항암제를 더한 군에서 더 많았다. 추적 중앙값은 40.9개월이었다.", "units": [ "U-ATOMIC" ] }, { "claim": "같은 dMMR 결장암의 수술 전 면역항암 시험은 대조군 없이 111명 중 75명(68%)의 병리학적 완전반응을 보고했다. 두 시험은 설계와 평가변수가 달라 직접 견주지 않는다.", "units": [ "U-NICHE2" ] } ], "objection": "위험비가 0.50이고 무병 생존은 결장암 보조 치료에서 전체 생존을 잘 대리해 왔으므로, 전체 생존을 기다리지 않고 이득을 확정해도 된다는 견해가 있다.", "changesMind": "이 시험의 전체 생존이 공개되거나, 수술 전 면역항암과 보조 병용을 무작위로 비교한 결과가 나오면 다시 판단한다.", "next": [ "이 시험의 전체 생존과 장기 독성 후속 보고를 감시한다", "수술 전 면역항암의 무작위 시험 등록 정보를 확인한다" ], "holdStatus": "held" }, { "id": "QP-88", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "units": [ "U-PALOMA2", "U-PALOMA3", "U-ML2", "U-ML3", "U-ML7", "U-MONARCH2" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "한 계열 세 약의 수명 연장 성적이 엇갈렸다", "question": "CDK4/6 억제제 세 약의 3상 시험에서 전체 생존 결과가 갈린 것을 약 자체의 차이로 볼 수 있는가?", "judgment": "아직 그렇게 보지 않는다. 팔보시클립의 두 시험은 전체 생존 개선이 유의하지 않았고 리보시클립의 세 시험과 아베마시클립의 한 시험은 유의했다는 사실을 기록한다. 그러나 시험마다 대상과 병용 약, 추적, 자료 누락이 달랐고 약끼리 직접 비교한 무작위 시험은 이 라이브러리에 없으므로, 차이의 원인이 약인지 시험 조건인지는 보류한다.", "basis": [ { "claim": "팔보시클립은 1차 치료 시험에서 전체 생존 위험비 0.96, 내분비 치료 뒤 시험에서 0.81이었고 둘 다 유의하지 않았다. 1차 시험은 생존 여부를 모르는 환자가 13.3% 대 21.2%로 두 군에서 달랐다.", "units": [ "U-PALOMA2", "U-PALOMA3" ] }, { "claim": "리보시클립은 세 시험 모두에서, 아베마시클립은 내분비 치료 뒤 시험에서 전체 생존이 유의하게 길었다(위험비 0.71~0.76 범위).", "units": [ "U-ML2", "U-ML3", "U-ML7", "U-MONARCH2" ] }, { "claim": "여섯 시험은 폐경 상태, 병용 내분비 약, 앞선 치료가 서로 다르다. 시험 사이의 수치를 나란히 놓는 것은 무작위 비교가 아니다.", "units": [ "U-PALOMA2", "U-ML7", "U-MONARCH2" ] } ], "objection": "같은 설계에 가까운 시험들에서 한 약만 반복해서 생존 이득을 보이지 못했으므로, 우연이나 시험 조건보다 약의 차이로 보는 것이 자연스럽다는 견해가 있다.", "changesMind": "세 약을 직접 비교한 무작위 시험이 공개되거나, 개별 환자 자료로 대상과 추적을 맞춘 통합 분석이 공개되면 다시 판단한다.", "next": [ "세 약을 직접 비교한 무작위 시험의 등록 정보를 확인한다", "팔보시클립 1차 시험의 생존 자료 누락이 결과에 준 영향을 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-89", "program": "gastric", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-ESOPEC", "U-NeoAEGIS", "U-CM577" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "접합부암 수술 전 요법 비교는 시대가 어긋난다", "question": "식도·위식도접합부 선암에서 수술 전후 항암이 수술 전 항암방사선보다 생존이 좋았다는 결과를 지금의 표준에 그대로 적용할 수 있는가?", "judgment": "한 시험에서 수술 전후 항암(FLOT)의 3년 생존이 더 높았다는 결과를 기록한다. 다만 그 시험의 항암방사선군은 수술 뒤 면역항암제를 받지 않았고, 앞선 다른 시험은 차이 없이 조기 종료됐다. 항암방사선 뒤 잔존암에 면역항암제를 더하는 전략과 견준 우열은 보류한다.", "basis": [ { "claim": "수술 전후 FLOT 대 수술 전 항암방사선 시험에서 3년 전체 생존은 57.4% 대 50.7%(위험비 0.70)였다.", "units": [ "U-ESOPEC" ] }, { "claim": "앞선 시험은 3년 전체 생존 55% 대 57%로 차이가 없어 조기 종료됐고, 병리학적 완전반응은 항암방사선 쪽이 더 많았다. 이 시험의 항암군 다수는 FLOT 이전의 요법을 받았다.", "units": [ "U-NeoAEGIS" ] }, { "claim": "항암방사선과 수술 뒤 잔존암이 있는 환자에게 니볼루맙을 더하면 무병 생존이 길어졌다. 이 전략은 위 두 비교 시험의 항암방사선군에 포함되지 않았다.", "units": [ "U-CM577" ] } ], "objection": "수술 뒤 면역항암제의 전체 생존 이득은 아직 확인되지 않았으므로, 전체 생존 차이를 보인 무작위 시험의 결론을 그대로 따르는 것이 맞다는 견해가 있다.", "changesMind": "수술 전후 항암과 항암방사선 뒤 면역항암제 전략을 직접 비교한 무작위 결과가 공개되거나, 니볼루맙 시험의 전체 생존 결과가 공개되면 다시 판단한다.", "next": [ "니볼루맙 보조요법 시험의 전체 생존 보고를 확인한다", "두 비교 시험에서 접합부 종양만의 결과가 보고됐는지 원문에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-90", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-NALA", "U-HER2CLIMB02", "U-PHILA", "U-HER2CLIMB" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "진행만 늦춘 HER2 추가 약은 수명 이득 미정", "question": "HER2 양성 전이성 유방암에서 HER2 표적 경구약을 더해 무진행 생존이 늘어난 결과를 생존 이득으로 볼 수 있는가?", "judgment": "시험마다 다르게 기록한다. 전체 생존 개선까지 보고한 시험과 무진행 생존만 개선한 시험을 구분하고, 뒤의 경우에는 생존 이득을 보류한다. 독성이 뚜렷이 늘어난 조합은 무진행 생존 몇 달의 차이만으로 이득이라 판단하지 않는다.", "basis": [ { "claim": "네라티닙 시험은 무진행 생존 위험비 0.76이었지만 전체 생존은 유의하지 않았다(위험비 0.88). 투카티닙을 T-DM1에 더한 시험은 무진행 생존이 7.4개월에서 9.5개월로 늘었으나 전체 생존 중간 분석의 위험비는 1.23이었고 3등급 이상 이상반응이 41.2%에서 68.8%로 늘었다.", "units": [ "U-NALA", "U-HER2CLIMB02" ] }, { "claim": "피로티닙 1차 치료 시험은 전체 생존 개선을 보고했다(위험비 0.64, 명목 유의). 이 시험의 대조군에는 다른 지역의 표준인 퍼투주맙이 없었다. 투카티닙을 트라스투주맙·카페시타빈에 더한 앞선 시험은 무진행 생존(위험비 0.54)과 함께 전체 생존 개선도 보고했다(2년 생존율 44.9% 대 26.6%, 위험비 0.66, P=0.005).", "units": [ "U-HER2CLIMB", "U-PHILA" ] }, { "claim": "네 시험은 치료 차수, 병용 약, 대조군이 모두 달라 서로의 결과를 대신하지 못한다.", "units": [ "U-NALA", "U-HER2CLIMB02", "U-PHILA", "U-HER2CLIMB" ] } ], "objection": "뇌 전이 환자에서의 효과처럼 전체 생존으로 잡히지 않는 이득이 있고, 후속 치료가 많은 질환에서는 무진행 생존이 더 적절한 평가변수라는 견해가 있다.", "changesMind": "투카티닙과 T-DM1 병용 시험의 최종 전체 생존이 공개되면 그 조합에 대한 판단을 다시 쓴다. 뇌 전이 환자에서 사전에 정한 평가변수의 결과가 수치로 보고되면 그 집단을 따로 판단한다.", "next": [ "투카티닙·T-DM1 시험의 뇌 전이 하위군 수치를 원문에서 확인한다", "피로티닙 시험 결과를 퍼투주맙 포함 표준과 견줄 자료가 있는지 찾는다" ], "holdStatus": "held" }, { "id": "QP-91", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-ESTIMABL2", "U-T-IoN", "U-T-HiLo", "U-T-ESTIMABL1" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "요오드 생략의 비열등성은 5년 지표까지 봄", "question": "저위험 분화 갑상선암에서 수술 뒤 방사성요오드를 생략해도 된다는 무작위 시험 결과는 어느 환자와 어느 기간까지 확인됐는가?", "judgment": "갑상선 전절제를 받은 저위험 환자에서 3년과 5년의 영상·검사 지표로 본 비열등성까지 확인된 것으로 기록한다. 두 시험 모두 사건이 적어 더 큰 종양이나 림프절 전이가 있는 환자의 결과는 수가 매우 적다. 그 환자군과 5년 이후의 재발, 전절제보다 작은 수술을 받은 환자에 대해서는 보류한다.", "basis": [ { "claim": "프랑스 시험에서 사건이 없는 환자는 3년에 95.6% 대 95.9%, 5년에 93.2% 대 94.8%였고 두 시점 모두 비열등성 기준을 충족했다. 사건의 다수는 검사 수치 이상이었다.", "units": [ "U-T-ESTIMABL2" ] }, { "claim": "영국 시험에서 5년 무재발 비율은 생략군 97.9% 대 시행군 96.3%였다. 재발은 모두 17건이었고, pT3 종양 46명과 N1a 47명에서 재발 비율이 더 높게 관찰됐다.", "units": [ "U-T-IoN" ] }, { "claim": "앞선 두 시험은 저용량과 고용량의 제거 성공률이 비슷하다는 것을 보였을 뿐 생략을 시험하지 않았다. 평가 시점도 한 해 이내였다.", "units": [ "U-T-HiLo", "U-T-ESTIMABL1" ] } ], "objection": "두 나라의 독립된 시험이 같은 결론에 이르렀고 재발 자체가 드무므로, 저위험 환자의 요오드 생략은 더 긴 추적을 기다릴 필요 없이 확립됐다는 견해가 있다.", "changesMind": "두 시험의 더 긴 추적 결과가 공개되거나, 더 큰 종양이나 림프절 전이 환자만을 대상으로 한 무작위 비교가 나오면 범위를 다시 쓴다.", "next": [ "영국 시험의 장기 추적 보고를 감시한다", "프랑스 시험 원문에서 사건 정의별 환자 수를 확인한다" ], "holdStatus": "held" }, { "id": "QP-92", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-PTMCSurveillanceKR18", "U-PMCObserveJP10" ], "asOf": "2026-10-11", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-11", "title": "관찰 코호트의 종양 증가 비율은 기준이 다르다", "question": "저위험 유두암을 수술 없이 지켜본 네 코호트가 보고한 종양 증가 비율을 하나의 진행 위험으로 묶을 수 있는가?", "judgment": "묶지 않는다. 지름 기준으로는 3.5%, 3.8%, 7%가, 부피 기준으로는 23.2%가 보고되어 측정 기준에 따라 숫자가 크게 달라진다. 세 코호트가 관찰 중 원격 전이가 없었다고 보고한 점과 세 코호트에서 젊은 환자의 증가가 더 잦았다는 점은 함께 기록한다. 한 사람의 진행 위험을 나타내는 단일 수치는 보류한다.", "basis": [ { "claim": "지름 증가는 미국 코호트 291명 중 3.8%, 국내 코호트 370명 중 3.5%였고, 일본 단일 기관 자료에서는 병변 300개 중 7%가 커졌다.", "units": [ "U-PTCSurveillanceUS17", "U-PTMCSurveillanceKR18", "U-PMCObserveJP10" ] }, { "claim": "국내 코호트에서 부피 증가는 23.2%였고 다섯 해 누적으로는 36.2%였다. 같은 환자들에서 지름 증가는 3.5%였다.", "units": [ "U-PTMCSurveillanceKR18" ] }, { "claim": "일본의 큰 코호트 1235명, 미국 코호트, 일본 단일 기관 자료는 관찰 중 원격 전이가 없었다고 보고했다. 국내 코호트 초록은 뒤늦게 수술한 58명의 사유를 적었고 원격 전이는 따로 적지 않았다.", "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-PMCObserveJP10", "U-PTMCSurveillanceKR18" ] }, { "claim": "세 코호트에서 젊은 환자의 증가나 진행이 더 잦았다. 국내 코호트는 갑상선염 동반 여부에 따른 크기 변화 차이가 유의하지 않았다고 적었으나 수치는 싣지 않았다.", "units": [ "U-PTMCObserveAge14", "U-PTCSurveillanceUS17", "U-PTMCSurveillanceKR18" ] } ], "objection": "측정 기준이 달라도 네 코호트 모두 대다수 종양이 커지지 않았다는 방향은 같으므로, 대략의 범위를 하나로 제시하는 편이 실용적이라는 견해가 있다.", "changesMind": "같은 측정 기준과 같은 추적 간격으로 여러 코호트를 합친 분석이나, 갑상선염 동반 환자의 수치를 따로 보고한 관찰 자료가 공개되면 다시 쓴다.", "next": [ "국내 코호트 원문에서 갑상선염 동반 여부별 증가 비율을 확인한다", "네 코호트의 증가 정의와 초음파 간격을 원문에서 대조한다" ], "holdStatus": "held" }, { "id": "QP-94", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-INFLUENCEBE26" ], "asOf": "2026-10-12", "status": "판단 기록됨", "title": "같은 예측식도 사건에 따라 성능이 갈림", "question": "한 재발 예측식이 국소·구역 재발을 잘 구분하고 보정 오차도 작다면, 반대쪽 유방암까지 잘 예측하며 그 점수로 추적 검사를 바꾸는 것이 이롭다고 볼 수 있을까?", "judgment": "그렇게 묶지 않는다. 저자가 보고한 국소·구역 재발의 판별 성능과 반대쪽 유방암의 성능을 사건별로 분리한다. 선행 전신치료를 받지 않은 집단에서는 후자의 판별력이 낮았다는 결과도 남긴다. 작은 절대 보정 오차만으로 낮은 위험 구간의 과대예측을 지우거나, 치료 이력이 다른 집단의 성능 차이를 치료의 인과효과로 해석하는 범위는 보류한다. 추적 전략의 환자 이득은 따로 검증해야 한다.", "basis": [ { "claim": "벨기에 단일 기관에서 평가한 예측식은 국소·구역 재발과 반대쪽 유방암을 서로 다른 사건으로 다뤘다. 선행 전신치료를 받지 않은 집단의 반대쪽 유방암 판별력은 낮았지만 다른 사건·집단의 판별력은 더 높았다고 보고했다.", "units": [ "U-INFLUENCEBE26" ] }, { "claim": "대부분 하위군의 절대 보정 오차가 작았으나 그림에서는 특히 낮은 예측 위험에서 과대추정이 나타났다. 초록은 사건 수·불확실성·경쟁 사건 처리와 점수에 따른 추적 변경의 실제 결과를 충분히 제공하지 않는다.", "units": [ "U-INFLUENCEBE26" ] } ], "objection": "다른 나라에서의 평가와 사건별 결과는 위험에 맞춘 후속 검증을 설계하는 데 도움이 될 수 있다. 다만 반대쪽 유방암과 국소 재발을 합치거나 점수 순위만으로 개인의 추적 횟수를 정하면 낮은 판별력과 과대추정의 영향을 가릴 수 있다.", "changesMind": "사건 정의·추적·경쟁 사건과 자료 겹침을 감사한 고정 모형을 적격 독립 자료에서 다시 평가하고, 사건별 보정·오분류·불확실성이 확인되면 예측 범위를 갱신한다. 검사 전략의 이득은 전향적인 적절한 비교가 따로 필요하다.", "next": [ "국소 재발과 반대쪽 유방암의 연도별 사건 수·분모·검열부터 원문에서 확인한다", "낮은 위험 구간의 과대예측과 경쟁 사건 처리·개발 자료 겹침을 대조한다", "추적 기준값과 환자 결과의 비교는 모형의 판별 성능과 별도 과제로 둔다" ], "by": "Codex (GPT-6)", "added": "2026-10-12", "holdStatus": "held" }, { "id": "QP-95", "program": "gastric", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-G" ], "units": [ "U-HER2Lactylation26" ], "asOf": "2026-10-13", "status": "판단 기록됨", "title": "위암의 락틸화 차단은 세포·동물 근거임", "question": "HER2의 락틸화를 막아 트라스투주맙 반응이 좋아졌다면, 이미 다른 질환에 승인된 약을 이용하는 위암 병용 치료를 검증된 접근으로 볼 수 있을까?", "judgment": "환자에서 검증된 병용 치료로 두지 않는다. 위암 모형에서 수용체의 변형·안정화와 항체 내성이 연결되고 차단 개입이 반응을 높였다는 실험 근거를 후보로 기록한다. 환자 예후와의 연관성은 치료 이득과 분리한다. 다른 질환의 약제 승인은 위암에서 필요한 노출·정상 조직 위해·상호작용·생존 이득을 대신하지 않으며 유방암으로의 적용도 보류한다.", "basis": [ { "claim": "저자는 HER2의 락틸화가 수용체 안정화와 다른 수용체와의 상호작용을 높인다고 보고했고, 세포의 약제 반응과 동물의 항종양 효과를 차단 실험으로 평가했다.", "units": [ "U-HER2Lactylation26" ] }, { "claim": "환자 표본에서는 높은 락틸화와 나쁜 예후가 연관됐지만, 초록에는 인간 병용 시험이나 표본 수·효과 크기·약물 노출과 안전성 구간이 없다.", "units": [ "U-HER2Lactylation26" ] } ], "objection": "수용체 변형을 겨냥한 개입과 기존 약제의 실험 반응은 후속 검증의 출발점이 될 수 있다. 다만 대사 전반을 바꾸는 개입의 효과를 해당 변형에만 돌리거나 실험 농도를 환자에서 달성할 수 있다고 가정하면 후보의 우선순위가 왜곡된다.", "changesMind": "독립적인 위암 모형에서 변형 부위의 인과성과 기능 회복 실험이 확인되고, 임상에서 달성 가능한 노출과 정상 조직 위해·병용 상호작용을 검토하면 전임상 후보의 범위를 갱신한다. 환자 치료 이득은 적격 인간 비교 연구가 공개돼야 별도로 판단한다.", "next": [ "원문의 변형 확인법과 부위별 개입·기능 회복 실험을 읽는다", "실험 농도·종양 노출·정상 조직 위해와 전달 조건을 분리해 확인한다", "환자 예후 연관성과 병용 치료의 효과를 다른 검증 과제로 둔다" ], "by": "Codex (GPT-6)", "added": "2026-10-13", "holdStatus": "held" }, { "id": "QP-96", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [ "BM-HR" ], "units": [ "U-CDK1Dynamics26" ], "asOf": "2026-10-13", "status": "판단 기록됨", "title": "효소의 재상승과 치료 선택 기준을 구분함", "question": "세포 주기 억제 뒤 다른 효소의 활성이 다시 높아지고 환자의 내성 표본에서도 증가했다면, 그 효소를 측정해 치료를 고르거나 추가 억제를 결정할 근거가 충분할까?", "judgment": "내성과 연결된 후보 신호까지 기록하고 치료 선택 기준으로의 전환은 보류한다. 효소 활성·발현량·인산화 부위는 서로 다른 관측값이며, 환자의 나쁜 예후와 연관된 표지가 특정 치료의 이득을 구분한다는 뜻도 아니다. 치료 중 적응 반응과 장기 내성을 구별하고, 추가 억제의 정상 조직 위해와 환자 결과를 따로 검증해야 한다.", "basis": [ { "claim": "저자는 동물의 실시간 효소 관측과 세포 실험에서 억제 후 재상승을 관찰했고, 환자 상관 분석에서는 비반응 또는 내성과 효소 측정값의 연결을 보고했다.", "units": [ "U-CDK1Dynamics26" ] }, { "claim": "초록에는 임상 검사 기준값·환자 표본 수·효과 구간이나 표지에 따라 치료 이득이 달라지는 비교가 없다. 공개 자료 개요 주소도 이번에는 정상 기록 대신 브라우저 확인 화면을 반환해 자료 접근·실행으로 세지 않았다.", "units": [ "U-CDK1Dynamics26" ] } ], "objection": "반복 측정과 실험 개입이 이어지면 단일 시점의 발현량보다 적응 과정을 잘 설명할 가능성은 있다. 다만 활성이 떨어지지 않은 종양이 원래 증식성이 높았는지, 측정 시점과 이전 치료가 영향을 줬는지 확인하지 않으면 인과성과 예측성을 과대평가할 수 있다.", "changesMind": "측정법과 채취 시점을 고정한 독립 자료에서 예후 인자와 치료 이력을 조정하고, 표지와 치료 효과의 상호작용이 확인되면 예측 표지의 범위를 갱신한다. 추가 억제의 임상 이득은 정상 조직 위해를 포함한 적격 비교 연구가 따로 필요하다.", "next": [ "원문에서 활성·발현·인산화 측정법과 검체 시점을 대조한다", "환자 집단의 겹침·반응 정의·예후 인자와 치료 이력을 확인한다", "치료 중 적응과 장기 내성 및 추가 억제의 위해를 분리해 설계한다" ], "by": "Codex (GPT-6)", "added": "2026-10-13", "holdStatus": "held" }, { "id": "QP-93", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-CLASP26" ], "asOf": "2026-10-11", "status": "판단 기록됨", "title": "병리 판별력은 치료 성과와 따로 평가함", "question": "병리 영상과 여러 언어모델이 만든 개념을 결합해 항암치료 뒤 완전반응을 잘 구분했다면, 적은 자료로 치료를 바꾸어 환자의 결과도 개선할 수 있다고 볼 수 있을까?", "judgment": "외부 저자가 보고한 병리 반응의 판별 성능으로 기록한다. 언어모델의 합의와 영상의 설명 가능성은 임상 이득이나 내성 기전의 증명이 아니다. 코호트 독립성·학습 자료 노출·전처리와 모형 고정을 대조하기 전에는 자체 재현으로 세지 않고, 소수 학습 결과를 작은 환자 자료만으로 안전하게 운영할 수 있다는 근거로 해석하는 범위를 보류한다.", "basis": [ { "claim": "치료 전 병리 영상·임상 정보·언어모델의 병리 개념을 결합했고 내부 시험과 외부 검증의 판별 수치를 보고했다. 비교 모형보다 수치상 높았다는 설명만으로 차이의 통계적 유의성을 확정하지 않는다.", "units": [ "U-CLASP26" ] }, { "claim": "초록은 적은 학습 사례의 성능도 제시하지만 표본 선정·반복 변동·검증 집합별 분모가 충분히 설명되지 않는다. 보정·의사결정 기준·치료 변경의 이득과 정량적 예후 평가는 초록에서 확인되지 않는다.", "units": [ "U-CLASP26" ] } ], "objection": "다기관 검증과 병리 지식을 반영한 설계는 새로운 검증 후보를 고르는 데 도움이 될 수 있다. 다만 높은 판별력과 설명 가능한 영역이 보인다는 사실만으로 치료 결정을 바꾸는 것이 안전하다고 결론낼 수는 없다.", "changesMind": "환자와 사전학습 자료의 겹침 및 정보 유입을 감사하고 고정한 모형을 독립 자료에서 재실행한 뒤, 보정·오분류·기준 모형 대비 차이가 확인되면 계산 검증 범위를 갱신한다. 치료 변경의 이득은 전향적인 적절한 비교가 따로 필요하다.", "next": [ "원 코드·환자 단위 분할·사전학습 출처·언어 개념 생성 시점부터 확인한다", "소수 학습의 표본 선택·반복 변동과 외부 집합별 분모를 대조한다", "보정·오분류 위험과 치료 변경의 결과는 판별 수치와 별도로 검증한다" ], "by": "Codex (GPT-6)", "added": "2026-10-11", "holdStatus": "held" }, { "id": "QP-97", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-MetastaticLatency26" ], "asOf": "2026-10-14", "status": "판단 기록됨", "title": "전이의 변이 시점과 재발 차단은 별개", "question": "전이 종양에서 새로 검출된 변이의 축적 시점이 재발까지의 시간 차이를 설명한다면, 변이 축적을 막아 재발을 예방할 수 있다고 결론낼 수 있을까?", "judgment": "그렇게 결론내리지 않는다. 원발·전이 종양의 분석에서 변이 시점과 잠복기의 연관을 설명하는 모형으로 기록한다. 검출된 변이가 퍼진 뒤 생겼다는 추론, 개별 환자의 미래 재발 예측, 개입으로 재발을 줄인다는 인과 이득은 각각 검증이 다르다. 표본 선정·검출 감도·이전 치료와 모형 가정을 확인하기 전에는 특정 변이 경로를 예방 치료의 검증된 표적으로 두지 않는다.", "basis": [ { "claim": "저자는 원발과 전이 종양의 유전체를 분석해 퍼진 뒤 획득한 것으로 추정되는 변이와 전이 부위별 경로를 보고했다. 변이 시점에 따른 잠복기 설명은 이미 관측된 자료에서 나온 결과다.", "units": [ "U-MetastaticLatency26" ] }, { "claim": "초록은 변이 경로의 빈도와 잠복기 변동의 설명을 제시하지만, 개인의 미관측 재발 시점에 대한 독립 평가나 변이 축적을 막은 인간 비교 연구는 제공하지 않는다. 종양·짝·환자의 분모도 원문에서 따로 확인해야 한다.", "units": [ "U-MetastaticLatency26" ] } ], "objection": "전이의 시간 조건을 설명하는 모형은 늦은 재발의 기전을 좁히는 데 도움이 될 수 있다. 다만 이미 전이한 사람의 생검을 분석한 선택 조건과 치료 후 검출 변이를 무시하면 새 변이가 재발을 일으켰다는 인과성이나 예방 가능성을 과대평가할 수 있다.", "changesMind": "자료 선정과 전이·잠복기의 정의 및 변이 시점 추론을 감사하고, 고정한 경로와 모형을 별도 자료에서 평가해 불확실성과 대안 설명이 비교되면 관측 범위를 갱신한다. 재발 차단의 이득은 정상 조직 위해를 포함한 적격 개입 비교가 따로 필요하다.", "next": [ "전이·잠복기 정의와 환자·종양·짝의 분모를 원문에서 구분한다", "변이 시점 추론·검출 감도·이전 치료와 경로 선택의 가정을 확인한다", "모형 설명력과 독립 미래 예측 및 재발 차단의 개입 이득을 분리한다" ], "by": "Codex (GPT-6)", "added": "2026-10-14", "holdStatus": "held" }, { "id": "QP-98", "program": "breast", "targets": [], "biomarkers": [ "BM-HR" ], "units": [ "U-Ganetespib26" ], "asOf": "2026-10-15", "status": "판단 기록됨", "title": "내성 병용의 음성 결과와 위해를 함께 읽음", "question": "전임상에서 내성 극복 후보였던 단백질 안정화 차단제를 내분비치료에 더한 무작위 시험이 음성이면, 어떤 범위까지 가설을 수정해야 할까?", "judgment": "시험의 내분비 내성 전이성 유방암 맥락에서는 병용이 진행 억제를 개선했다는 근거가 없고 위해가 늘었다고 기록한다. 전임상 활성을 사람의 병용 이득으로 옮긴 기대를 낮춘다. 다만 작은 시험의 차이 미검출을 두 방식의 동등성이나 해당 기전 전체의 부정으로 넓히지 않는다. 현대 치료 순서와 변이별 선택, 재발 예방으로의 외삽은 보류한다.", "basis": [ { "claim": "저자는 풀베스트란트 단독과 가네테스핍 병용의 무진행생존 개선을 확인하지 못했고 병용의 설사와 메스꺼움 증가를 보고했다. 레지스트리와 초록의 통계 유형 표기가 달라 원문 대조 전 같은 추정량으로 합치지 않았다.", "units": [ "U-Ganetespib26" ] }, { "claim": "치료 중 생검의 변이와 전사 아형은 탐색적 관찰이며 시험의 실패 원인이나 변이 기반 치료 선택을 직접 입증하지 않는다.", "units": [ "U-Ganetespib26" ] } ], "objection": "표적에 맞는 노출이나 환자 선택이 달랐다면 다른 결과가 나올 가능성은 남는다. 그렇더라도 실제 음성 결과와 위해를 지우고 세포 실험만으로 임상 병용을 우선할 수는 없다.", "changesMind": "원문에서 군별 추정과 불확실성·노출·위해를 대조하고, 독립적인 적격 비교가 미리 정한 대상과 지표에서 이득을 보이면 해당 범위의 판단을 갱신한다. 탐색 생검의 사후 선택만으로 보류를 해제하지 않는다.", "next": [ "원문의 군별 무진행생존과 위해 분모·등급을 확인한다", "등록 계획과 검열·치료 이력·노출을 대조한다", "탐색 생검의 선택 조건과 변이별 치료 상호작용을 분리한다" ], "by": "Codex (GPT-6)", "added": "2026-10-15", "holdStatus": "held" }, { "id": "QP-99", "program": "breast", "targets": [ "ESR1" ], "biomarkers": [ "BM-ESR1" ], "units": [ "U-ESR1VariantTOT26" ], "asOf": "2026-10-15", "status": "판단 기록됨", "title": "변이별 투약 지속기간은 비교 약효와 다름", "question": "수용체 변이 종류에 따라 엘라세스트란트 투약이 빨리 끝났다는 보험 청구 분석을, 그 변이에서 약효가 낮거나 다른 약이 더 좋다는 근거로 볼 수 있을까?", "judgment": "변이별 투약 지속기간과 분자 신호의 관찰 연관성으로 기록한다. 약을 끝낸 시점은 영상 진행이나 사망과 같지 않고 중단 이유도 다양하다. 이전 치료와 변이의 동반·양, 자료 연결과 누락을 확인하기 전에는 약효의 인과 차이나 대체 약제의 우열로 바꾸지 않는다. 기존 무작위 시험의 결론도 이 관찰로 덮어쓰지 않는다.", "basis": [ { "claim": "저자는 보험 청구에서 엘라세스트란트 시작과 종료 사이 기간을 정하고 변이 유형 및 복수 변이에 따른 기간 차이를 보고했다. 종양 유전체 전체의 수는 투약 분석의 환자 분모와 구별해야 한다.", "units": [ "U-ESR1VariantTOT26" ] }, { "claim": "에스트로겐 경로 신호의 차이가 함께 관찰됐지만, 변이에 따라 치료를 배정한 무작위 비교나 다른 약제와의 변이별 상호작용은 이 초록에 없다.", "units": [ "U-ESR1VariantTOT26" ] } ], "objection": "실제 진료의 투약 기간은 내성이나 내약성을 반영하는 유용한 단서일 수 있다. 그러나 청구 종료를 진행으로 간주하거나 치료 차수와 보험 접근 차이를 빼면 임상 이득을 과대해석할 수 있다.", "changesMind": "원문의 환자·종양·투약 분모와 중단 이유·치료 이력·누락을 감사하고 독립 자료에서 고정한 변이와 지표의 관계가 재확인되면 관측 범위를 갱신한다. 약제 선택의 이득은 적격 비교와 치료 상호작용의 별도 검증이 필요하다.", "next": [ "종양과 환자 및 청구 연결·투약 분석의 분모를 구분한다", "중단 이유·이전 치료·복수 변이와 클론 비율을 확인한다", "투약 지속·영상 진행·생존과 변이별 비교 이득을 별도 평가한다" ], "by": "Codex (GPT-6)", "added": "2026-10-15", "holdStatus": "held" }, { "id": "QP-100", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-CRLMMultistate26" ], "asOf": "2026-10-16", "status": "판단 기록됨", "title": "재발 상태별 예후를 보조치료 효과와 구별함", "question": "간 전이 절제 뒤 재발 여부에 따른 상태 전이 모형이 예후를 설명하고 보조치료와 낮은 위험이 연관되면, 재발을 줄이는 치료 효과로 받아들일 수 있을까?", "judgment": "수술 후 상태별 예후를 설명한 관찰 모형으로 기록하고 보조치료의 인과 이득은 보류한다. 원문의 사망 비율은 재발한 환자들을 분모로 하므로 전체 환자의 사망 비율로 옮기지 않는다. 일정 시점까지 재발 없이 생존한 사람의 조건부 전망도 수술 시점 전체 환자나 미래 개인의 예측과 구분한다. 자료를 다시 분석하거나 치료 효과를 검증한 것으로 세지 않는다.", "basis": [ { "claim": "원문은 재발 뒤 사망의 분모를 명시하고 수술 시점을 기점으로 무재발·재발 후 생존·원인별 사망을 나누었다. 조잡한 발생 비율과 시간에 따른 상태 확률은 다른 값이다.", "units": [ "U-CRLMMultistate26" ] }, { "claim": "센터별 이질성과 결측·반복 재발·재발 뒤 치료의 공백이 있다. 보조치료의 배정과 시작 시점을 통제한 무작위 비교가 아니므로 전이별 위험 연관성을 치료 이득으로 확정하지 않는다.", "units": [ "U-CRLMMultistate26" ] } ], "objection": "재발을 중간 상태로 두면 단일 생존 지표에서 가려지는 차이를 보여 줄 수 있다. 그러나 여러 기관 자료와 정교한 모형도 치료 선택의 교란이나 사망 원인 오분류를 자동으로 제거하지 않는다.", "changesMind": "상태 전이와 기점·추적·결측·치료 시점을 감사하고 별도 자료에서 고정한 모형의 보정과 불확실성을 확인하면 관측 범위를 갱신한다. 치료 이득은 적절히 시간과 선택을 통제한 독립 비교가 필요하다.", "next": [ "재발·사망의 분모와 누적 발생·상태 확률을 구분한다", "수술 뒤 보조치료 시작과 선택 및 결측 처리 방식을 확인한다", "별도 자료의 모형 보정과 치료 효과 검증을 나누어 설계한다" ], "by": "Codex (GPT-6)", "added": "2026-10-16", "holdStatus": "held" }, { "id": "QP-101", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-S100RAGETDXd26" ], "asOf": "2026-10-16", "status": "판단 기록됨", "title": "내성의 공간 신호와 병용 검증은 별개", "question": "전이 병변의 공간 신호가 약제 저항성과 연결되고 세포·생쥐에서 차단 병용이 작동했다면, 사람의 내성을 되돌리는 치료로 볼 수 있을까?", "judgment": "공간 관측과 실험적 개입이 연결된 후보로 기록하며 인간 병용 효과는 보류한다. 같은 환자의 여러 병변은 독립 환자 수가 아니고, 첫 재평가의 안정질환 포함 반응 분류는 오래 지속되는 임상 이득과 다르다. 면역 결핍 생쥐의 전이 모형 결과를 면역계가 있는 종양이나 사람의 지연 치료로 그대로 옮기지 않는다. 성립하지 않은 모형도 검증 공백으로 보존한다.", "basis": [ { "claim": "저자는 저항성 병변의 염증 신호와 수용체 경로를 보고했고, 세포와 면역 결핍 생쥐에서 수용체 차단 병용의 활성을 시험했다. 임상 병용 비교는 수행한 것으로 보고되지 않았다.", "units": [ "U-S100RAGETDXd26" ] }, { "claim": "원문에서 면역 적격 이식 모형은 치료 없이 종양이 퇴행해 지연 개입을 시험할 수 없었고, 종적 생검도 없어 치료 중 획득 내성의 변화를 확인하지 못했다.", "units": [ "U-S100RAGETDXd26" ] } ], "objection": "부위가 다른 전이 병변의 일관된 신호와 실험 개입은 후보의 기전적 근거를 강화할 수 있다. 다만 공간 영역의 선택·같은 환자 내 상관·노출과 정상 조직 위해를 확인하기 전에는 임상 적용 준비도를 올릴 수 없다.", "changesMind": "독립 환자와 성립하는 면역 맥락의 모형에서 영역 선택·반복 병변·노출·위해를 고정해 재확인되면 실험 후보의 범위를 갱신한다. 인간 병용의 이득은 적격 비교에서 따로 판정한다.", "next": [ "환자와 병변·공간 영역의 분모와 분류 시점을 확인한다", "성립하지 않은 모형과 지연 개입·종적 생검의 공백을 남긴다", "독립 실험계의 노출·위해와 임상 병용 비교를 구분한다" ], "by": "Codex (GPT-6)", "added": "2026-10-16", "holdStatus": "held" }, { "id": "QP-102", "program": "gastric", "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI" ], "units": [ "U-NEONIPIGA" ], "asOf": "2026-10-17", "status": "판단 기록됨", "title": "장기 면역치료 추적과 수술 생략의 간극", "question": "불일치 복구 결핍 위암·위식도 접합부암의 수술 전후 면역치료에서 장기 생존이 관찰되면, 수술을 생략해도 된다는 근거가 될까?", "judgment": "장기 생존이 관찰됐다는 점은 기존 단일군 시험의 후속 근거로 갱신하되, 수술 생략의 안전성과 비교 생존 이득은 보류한다. 전체 등록 집단의 전체 생존과 수술 적격 집단의 무사건 생존은 분모가 다르다. 병리 완전반응, 수술하지 않은 일부 환자의 임상 완전반응, 장기 무사건 상태와 완치를 구분한다. 같은 시험의 후속 논문을 새 임상시험이나 독립 검증으로 세지 않는다.", "basis": [ { "claim": "장기 추적은 기존 시험의 생존과 재발·사망을 보고한다. 계획한 치료를 모두 받은 환자는 일부이며, 수술 뒤 사망과 치료 관련 위해를 장기 생존 수치에서 지우지 않는다.", "units": [ "U-NEONIPIGA" ] }, { "claim": "논문은 다른 연구의 수술 단독 결과보다 생존이 개선됐다는 명확한 근거를 제시하지 못했다고 밝힌다. 이는 무작위 우월성이나 동등성 비교가 아니며, 등록부와 논문의 생존 평가변수 정의도 대조가 필요하다.", "units": [ "U-NEONIPIGA" ] } ], "objection": "반응이 지속되고 재발이 드물게 관찰되면 장기 보존 전략을 시험할 근거는 강화된다. 그러나 단일군의 작은 표본과 선택된 미수술 환자의 경과만으로 표준 수술과의 차이나 안전한 생략 대상을 확정할 수 없다.", "changesMind": "원문과 변경 이력에서 사건 정의·분모·추적·구제 수술 및 위해를 확인하고, 사전 기준을 고정한 장기 보존 전략의 적절한 비교 결과가 나오면 해당 범위의 판단을 갱신한다.", "next": [ "생존 평가변수의 정의와 등록부 변경 이력을 대조한다", "미수술 집단의 선택·추적·구제 치료와 사망 원인을 확인한다", "장기 보존 전략의 비교 결과와 위해를 함께 평가한다" ], "by": "Codex (GPT-6)", "added": "2026-10-17", "holdStatus": "held" }, { "id": "QP-103", "program": "colorectal", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-AkkMSSCRC26" ], "asOf": "2026-10-18", "status": "판단 기록됨", "title": "미생물 제제의 반응 기여도는 아직 미정", "question": "면역치료 반응이 드문 현미부수체 안정형 전이 대장암에서 미생물 제제와 병용한 반응이 관찰되면, 그 제제가 사람의 내성을 되돌렸다고 볼 수 있을까?", "judgment": "초기 단일군 병용의 관찰 신호로 기록하고 제제 자체의 기여와 비교 이득은 보류한다. 등록부는 다른 항암제 병용도 허용하므로 미생물 제제와 면역치료만의 효과로 읽지 않는다. 등록 계획의 표본 수를 논문의 분석 분모로 바꾸거나 반응 수를 역산하지 않는다. 세포를 제거하는 면역 기전의 동물 실험과 사람의 반응 연관성도 구별한다.", "basis": [ { "claim": "논문은 동물의 대식세포·선천면역 기전과 사람의 초기 병용 반응을 함께 보고하지만, 받은 초록에는 임상 반응 분모·반응 지속·정량적 위해가 없다.", "units": [ "U-AkkMSSCRC26" ] }, { "claim": "공식 등록부는 단일군이며 미생물 제제 외에 면역치료와 표적약 또는 항암제·혈관 차단제의 병용을 허용한다. 현재 계획 정보와 논문의 실제 투여 조건을 추가 대조해야 한다.", "units": [ "U-AkkMSSCRC26" ] } ], "objection": "동물의 개입 기전과 사람의 관찰 반응이 이어지면 후속 비교를 설계할 이유는 된다. 그러나 병용 구성·대조군·반응 평가와 위해를 알기 전에는 제제의 임상 기여를 분리할 수 없다.", "changesMind": "실제 투여 구성과 반응·안전성 분모 및 장기 추적을 확인하고, 같은 배경 치료에서 제제의 추가 기여를 구분하는 적격 비교가 나오면 그 범위에서 갱신한다.", "next": [ "등록 계획과 실제 투여 구성·분석 분모를 대조한다", "반응 평가·지속기간·등급별 위해를 확인한다", "같은 배경 치료에서 제제 추가의 비교 결과를 기다린다" ], "by": "Codex (GPT-6)", "added": "2026-10-18", "holdStatus": "held" }, { "id": "QP-104", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-MechanisticRelapse26" ], "asOf": "2026-10-19", "status": "판단 기록됨", "title": "잠재 재발 모형의 설명과 실측 사이", "question": "병리 정보에서 초기 전이 세포량과 증식률을 추정하는 재발 모형이 기존 통계모형과 비슷하게 순위를 맞추면, 실제 잠복 전이 기전을 측정하고 개인의 재발 시기를 검증했다고 볼 수 있을까?", "judgment": "설명 구조를 가진 계산 모형의 내부 평가로 기록하고, 잠재 변수의 생물학적 실측과 개인 예측의 검증은 보류한다. 문헌의 기준 표현형으로 절대 척도를 고정한 것은 추정 세포량이 실제로 맞음을 뜻하지 않는다. 같은 과거 코호트의 내부 교차검증과 기존 생존모형에 비슷한 순위 성능을 외부 검증이나 우위로 바꾸지 않는다.", "basis": [ { "claim": "논문은 병리 정보를 잠재 종양량과 증식률에 연결했으나, 미세환경 항목에 필요한 직접 측정값은 없어 그 부분의 구현을 남겨 두었다. 같은 자료의 대리 변수 탐색도 별도 검증은 아니다.", "units": [ "U-MechanisticRelapse26" ] }, { "claim": "보고한 평가는 과거 코호트의 내부 교차검증이며 기존 생존모형과 비슷한 순위 성능이다. 양수인 예측 시간을 내는 것과 개인별 재발 시기가 정확한 것은 다르다.", "units": [ "U-MechanisticRelapse26" ] } ], "objection": "예측을 병리 정보와 가정에 연결하면 검토할 질문을 분명하게 만들 수 있다. 다만 설명 가능한 수식 자체가 기전의 참임을 증명하지 않으며, 시간과 치료·아형 조건이 다른 집단에서의 보정과 위해는 별도 검토가 필요하다.", "changesMind": "입력·기점·검열·선택과 적합 절차를 감사하고, 고정한 모형을 독립 자료에서 기준모형과 비교해 보정과 불확실성을 확인하면 예측의 적용 범위를 갱신한다. 생물학적 잠재량은 별도의 실제 측정과 대조해야 한다.", "next": [ "같은 자료를 이용한 선택·적합과 내부 검증 절차를 감사한다", "독립 자료의 적격성·중복·시간 기점과 고정 모형을 확인한다", "순위 성능·절대 위험 보정·잠재 변수의 실측을 나누어 평가한다" ], "by": "Codex (GPT-6)", "added": "2026-10-19", "holdStatus": "held" }, { "id": "QP-105", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-PaxalisibBrain26" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-20", "title": "뇌 도달 약제의 병용에서도 멈춘 반응", "question": "뇌에 도달하는 경로 억제제가 동물모형에서 종양을 줄였어도, 여러 치료를 받은 유방암 뇌전이 환자에게 병용했을 때 확인 반응이 없다면 다음 연구 판단을 어떻게 바꿔야 할까?", "judgment": "시험한 용량과 환자군에서 일차 반응 목표를 달성하지 못한 실패로 기록한다. 뇌 도달이나 전임상 기전만으로 사람의 효능을 유지하지 않는다. 다만 작은 단일군 결과로 모든 경로 억제 전략의 무효를 선언하지 않고, 투여 노출·용량 제한·대상 선택을 다시 구분한다. 뇌척수액 종양 신호의 연관성도 치료 변경의 이득으로 확대하지 않는다.", "basis": [ { "claim": "권장 용량 집단에서 확인된 중추신경계 반응이 없었고 무익성으로 연구가 종료됐다. 안전성 도입부 전체와 반응 평가 집단의 분모는 다르다.", "units": [ "U-PaxalisibBrain26" ] }, { "claim": "뇌척수액 종양 신호가 종양 부담 변화와 함께 움직였지만, 그 신호로 치료를 바꿔 환자 결과가 좋아졌다는 비교는 없다.", "units": [ "U-PaxalisibBrain26" ] } ], "objection": "치료 전력이 많고 표본이 작아 더 이른 치료 맥락이나 다른 투여법의 가능성까지 배제하지는 못한다. 그러나 그 가능성이 현재 병용의 실패를 성공으로 바꾸지는 않는다.", "changesMind": "고정한 용량·노출 조건과 적격 집단에서 별도 임상 연구가 재현 가능한 반응과 위해를 보여 주면 적용 범위를 갱신한다. 검사 기반 치료 변경은 미리 정한 전략의 비교 이득을 따로 확인해야 한다.", "next": [ "권장 용량의 노출·용량 제한과 등급별 위해를 대조한다", "반응 평가 분모와 두개 내·외 진행 정의를 확인한다", "뇌척수액 검사와 치료 변경 전략의 검증을 구분한다" ], "holdStatus": "held" }, { "id": "QP-106", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-HypoMastIMNI26" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-20", "title": "방사선 분할 단축을 지지하는 범위", "question": "내유방 림프절을 포함한 수술 후 방사선치료에서 분할 횟수를 줄인 군이 국소 제어의 비열등성을 보이면 생존과 장기 안전성도 같다고 판단할 수 있을까?", "judgment": "보고된 고위험 수술 후 환자군과 조사 범위에서 국소 제어의 비열등성과 급성 피부 독성 감소를 지지하는 결과로 기록한다. 생존의 우월성이나 동등성, 림프절 조사 생략, 드문 장기 심장 위해의 부재로 확대하는 판단은 보류한다. 무작위 배정 전체와 수정 분석 집단의 차이도 확인한다.", "basis": [ { "claim": "일차 국소 재발 평가에서 비열등성 기준을 충족했고 급성 중증 피부 독성이 적었다. 다른 생존 평가변수에서는 유의한 차이가 보고되지 않았다.", "units": [ "U-HypoMastIMNI26" ] }, { "claim": "보고한 수정 분석 집단은 무작위 배정 전체보다 작다. 초록만으로 비열등성 한계의 사전 고정과 제외 사유·계획 준수 분석의 일치를 확인할 수 없다.", "units": [ "U-HypoMastIMNI26" ] } ], "objection": "치료 횟수와 급성 독성 감소는 연구상 중요한 차이다. 다만 특정 범위의 비열등성이 모든 환자군·조사 기술·시간대의 동일한 효과와 위해를 보장하지는 않는다.", "changesMind": "잠근 분석계획의 한계와 근거, 제외 사유, 계획 준수 분석 및 장기 위해 감시를 확인하면 결과의 견고성과 적용 범위를 갱신한다. 생존 이득은 해당 평가변수의 별도 근거가 필요하다.", "next": [ "비열등성 한계와 사전 고정 시점을 원 계획에서 확인한다", "수정 분석 제외 사유와 계획 준수 분석을 대조한다", "드문 심폐 위해와 재건·조사 기술별 적용 조건을 살핀다" ], "holdStatus": "held" }, { "id": "QP-107", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-nacGSOXLong26" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-20", "title": "긴 추적이 남겨도 해결되지 않는 비교", "question": "수술 전 항암치료를 받은 위암 단일군의 생존자를 오랫동안 추적했다면, 짧은 수술 전 치료가 재발을 막고 완치에 기여한 정도도 알 수 있을까?", "judgment": "한 코호트의 장기 경과와 치료 이행을 보여 주는 자료로 기록한다. 수술 전 치료·수술·수술 후 치료와 환자 선택이 함께 있어 짧은 수술 전 과정의 독립 기여와 다른 요법 대비 이득은 보류한다. 생존자를 오래 관찰한 사실과 전체 환자의 완치도 구분한다.", "basis": [ { "claim": "보고는 단일군의 뒤이은 추적이며 수술 후 보조치료의 시작과 완료가 같지 않았다. 다른 치료군과의 무작위 비교가 없다.", "units": [ "U-nacGSOXLong26" ] }, { "claim": "늦은 중증 위해가 기록되지 않았어도 체계적으로 조사하지 않았다는 한계가 명시됐다. 추적 누락이 없다는 사실로 그 한계를 지우지 않는다.", "units": [ "U-nacGSOXLong26" ] } ], "objection": "긴 추적은 단기 반응만으로 보이지 않던 경과를 보여 준다. 그러나 수술 후 림프절 상태의 예후 연관성을 치료 전 선택 기준으로 삼거나 단일군 생존을 비교 치료 효과로 읽을 수는 없다.", "changesMind": "원 등록·이전 보고·고정 계획의 평가변수와 분모를 대조하고 적절한 비교 연구가 해당 치료 과정의 이득과 위해를 검증하면 판단 범위를 갱신한다. 수술 후 예후 인자의 치료 전 선택 능력도 별도로 평가해야 한다.", "next": [ "원 등록의 무진행과 보고의 무재발 정의를 대조한다", "수술 후 치료 이행과 후속 치료의 영향을 확인한다", "늦은 위해의 실제 조사 방법과 비교 근거를 찾는다" ], "holdStatus": "held" }, { "id": "QP-108", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-ALASCCA" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-20", "title": "PI3K 변이 대장암의 아스피린 이득은 재발까지", "question": "PI3K 경로 변이가 있는 대장암에서 수술 뒤 저용량 아스피린이 재발을 줄였다는 결과는 어디까지 확인됐는가?", "judgment": "PIK3CA 주요 변이(엑손 9·20) 환자의 3년 재발 감소까지 확인된 것으로 기록한다. 다른 PI3K 경로 변이군의 결과와 무병 생존은 이차 평가변수로 적고, 전체 생존 이득과 변이가 없는 환자로의 확대는 보류한다. 중대한 이상반응이 아스피린군에서 더 많았다는 점을 함께 적는다.", "basis": [ { "claim": "주요 변이군의 3년 누적 재발은 아스피린 7.7%, 위약 14.1%였다(위험비 0.49, 95% 신뢰구간 0.24~0.98). 같은 군의 무병 생존 위험비는 0.61로 구간이 무효 값을 포함했다.", "units": [ "U-ALASCCA" ] }, { "claim": "다른 변이군에서도 3년 재발은 7.7% 대 16.8%(위험비 0.42)였으나 이차 평가변수다. 유전체 자료가 완전한 2980명 중 변이가 있는 환자는 1103명(37.0%)이었다.", "units": [ "U-ALASCCA" ] }, { "claim": "중대한 이상반응은 16.8% 대 11.6%였고, 초록에는 전체 생존 결과가 없다.", "units": [ "U-ALASCCA" ] } ], "objection": "관찰 연구와 같은 방향의 결과가 무작위 시험에서 나왔고 두 변이군의 효과 크기가 비슷하므로, PI3K 경로 변이가 있으면 아스피린의 이득은 이미 확립됐다는 견해가 있다.", "changesMind": "전체 생존 결과나 같은 설계의 다른 시험 결과가 공개되거나, 변이가 없는 환자를 무작위 배정한 결과가 나오면 다시 판단한다.", "next": [ "이 시험의 전체 생존 후속 보고를 감시한다", "원문에서 중대한 이상반응의 종류를 확인한다" ], "holdStatus": "held" }, { "id": "QP-109", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-CHALLENGE" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-20", "title": "운동 프로그램의 생존 연장은 한 시험의 결과", "question": "결장암 보조 항암 뒤 구조화된 운동 프로그램이 무병 생존을 늘렸다는 결과를 어떻게 기록하는가?", "judgment": "무병 생존 개선은 한 무작위 시험의 확인된 결과로 기록한다. 전체 생존은 저자들도 지지하는 결과로만 적었으므로 같은 수준으로 적는다. 필요한 운동의 양과 종류, 직장암·전이암·다른 암으로의 확대는 보류한다.", "basis": [ { "claim": "889명을 배정한 시험에서 추적 중앙값 7.9년에 무병 생존 위험비는 0.72였고, 5년 무병 생존은 80.3% 대 73.9%였다.", "units": [ "U-CHALLENGE" ] }, { "claim": "사망 위험비는 0.63, 8년 생존은 90.3% 대 83.2%였다. 근골격계 이상반응은 18.5% 대 11.5%로 운동군에서 더 많았다.", "units": [ "U-CHALLENGE" ] }, { "claim": "비교 대상은 지원을 받는 3년 프로그램과 교육 자료이며, 참여자와 연구진이 배정을 알 수 있는 설계다.", "units": [ "U-CHALLENGE" ] } ], "objection": "관찰 연구들과 방향이 같고 생존 차이까지 보였으므로, 운동은 이미 표준 보조 치료로 볼 수 있다는 견해가 있다.", "changesMind": "다른 나라에서 같은 질문의 무작위 결과가 나오거나, 운동량에 따른 결과 차이를 보고한 원문 분석이 확인되면 범위를 다시 쓴다.", "next": [ "원문에서 운동량 목표와 실제 달성 정도를 확인한다", "직장암이나 전이암 대상 운동 시험의 등록 정보를 찾는다" ], "holdStatus": "held" }, { "id": "QP-110", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-LEAP017", "U-AtezoTRIBE", "U-AkkMSSCRC26" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-20", "title": "pMMR 대장암 면역 병용은 시험마다 엇갈린다", "question": "불일치 복구 정상(pMMR) 전이 대장암에서 면역항암제 병용이 효과가 있다고 말할 수 있는가?", "judgment": "말하지 않는다. 이전 치료 뒤 렌바티닙 병용의 3상은 전체 생존에서 미리 정한 기준을 넘지 못했다. 일차 항암에 아테졸리주맙을 더한 2상은 무진행 생존 개선을 보고했지만 완화된 유의수준의 2상이고 대상이 불일치 복구 상태로 선별되지 않았다. 확증 시험 결과가 나올 때까지 이득은 보류한다.", "basis": [ { "claim": "이전 치료를 받은 환자 480명의 3상에서 생존 중앙값은 9.8개월 대 9.3개월(위험비 0.83, P=.0379, 기준 .0214)이었고 3등급 이상 치료 관련 이상반응은 58.4% 대 42.1%였다.", "units": [ "U-LEAP017" ] }, { "claim": "일차 치료 2상 218명에서 무진행 생존 중앙값은 13.1개월 대 11.5개월(위험비 0.69, 80% 신뢰구간 0.56~0.85)이었다. 초록은 불일치 복구 상태별 결과를 따로 싣지 않았다.", "units": [ "U-AtezoTRIBE" ] }, { "claim": "미생물 제제를 더한 초기 연구는 반응 분모와 위해 수치가 초록에 없어 비교 근거가 아니다.", "units": [ "U-AkkMSSCRC26" ] } ], "objection": "일차 치료에서 항암과 함께 쓰면 면역 반응을 끌어낼 수 있다는 2상 신호가 있으므로, 치료 시점에 따라 결론이 다르고 일차 병용은 이미 유망하다는 견해가 있다.", "changesMind": "일차 치료 병용의 3상 결과가 공개되거나, 2상의 pMMR 하위군 수치가 확인되면 다시 판단한다.", "next": [ "일차 치료 아테졸리주맙 병용의 확증 시험 등록 정보를 확인한다", "2상 원문에서 pMMR 하위군 결과를 확인한다" ], "holdStatus": "held" }, { "id": "QP-111", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-LENVA211", "U-T-SELECT" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-20", "title": "렌바티닙 시작 용량을 낮추면 반응이 줄었다", "question": "방사성요오드 불응 분화 갑상선암에서 렌바티닙을 낮은 용량으로 시작해도 효과가 같다고 볼 수 있는가?", "judgment": "볼 수 없다. 18 mg으로 시작한 군의 24주 반응률이 낮아 미리 정한 비열등성을 보이지 못했고, 3등급 이상 이상반응도 뚜렷이 줄지 않았다. 시작 용량을 낮추는 전략의 이득은 보류하고, 이 결과가 무진행·전체 생존에 대한 것이 아니라는 점을 함께 적는다.", "basis": [ { "claim": "24주 반응률은 24 mg 57.3%, 18 mg 40.3%였고 승산비 0.50(95% 신뢰구간 0.26~0.96)이었다.", "units": [ "U-T-LENVA211" ] }, { "claim": "3등급 이상 이상반응은 61.3% 대 57.1%로 차이 -4.2%(구간 -19.8~11.4)였다.", "units": [ "U-T-LENVA211" ] }, { "claim": "위약 대조 3상은 표준 시작 용량으로 무진행 생존 이득을 보고한 시험이며, 이상반응으로 투약을 끊은 비율도 보고했다.", "units": [ "U-T-SELECT" ] } ], "objection": "반응률 차이가 있어도 이상반응 때문에 결국 용량을 줄이는 환자가 많으므로, 처음부터 낮게 시작해도 장기 결과는 비슷할 것이라는 견해가 있다.", "changesMind": "두 시작 용량의 무진행 생존이나 전체 생존을 비교한 결과가 공개되면 다시 판단한다.", "next": [ "원문에서 군별 환자 수와 무진행 생존 보조 분석을 확인한다", "3상 원문에서 용량 감량 비율을 확인한다" ], "holdStatus": "held" }, { "id": "QP-112", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-Donafenib23", "U-T-ALTER01031", "U-T-SELECT", "U-T-DECISION", "U-T-ZETA", "U-T-EXAM", "U-T-LIBRETTO531" ], "asOf": "2026-10-20", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-20", "title": "중국 시험의 표적 억제제 결과는 대상 안에서", "question": "중국에서 시행된 도나페닙·안로티닙 위약 대조 시험의 위험비를 다른 나라 시험의 약과 견주어 순서를 정할 수 있는가?", "judgment": "정하지 않는다. 두 시험 모두 위약보다 무진행 생존이 길었다는 결과는 그 대상 안에서 기록한다. 대상 국가, 진행 확인 조건, 위약군 경과가 시험마다 달라 위험비를 나란히 놓은 약제 순위는 보류한다.", "basis": [ { "claim": "분화암 도나페닙 시험 191명에서 무진행 생존 중앙값은 12.9개월 대 6.4개월(위험비 0.39)이었다.", "units": [ "U-T-Donafenib23" ] }, { "claim": "수질암 안로티닙 2상 아흔한 명에서 무진행 생존 중앙값은 20.7개월 대 11.1개월(위험비 0.53)이었고, 위약군의 중앙값이 길었다.", "units": [ "U-T-ALTER01031" ] }, { "claim": "다른 나라의 분화암·수질암 위약 대조 시험들도 선정 기준과 위약군 경과가 서로 다르며, 이 근거 모음 안에서 약끼리 직접 비교한 무작위 시험은 수질암의 선택적 RET 억제제 시험뿐이다.", "units": [ "U-T-SELECT", "U-T-DECISION", "U-T-ZETA", "U-T-EXAM", "U-T-LIBRETTO531" ] } ], "objection": "위험비가 작고 같은 계열 약이므로, 도나페닙의 효과가 다른 다중 표적 억제제와 비슷하거나 더 낫다고 보는 견해가 있다.", "changesMind": "약끼리 직접 비교한 무작위 시험이나 개별 환자 자료를 합친 분석이 공개되면 다시 판단한다.", "next": [ "도나페닙 시험의 등록 번호를 원문에서 확인한다", "두 시험의 전체 생존 보고를 찾는다" ], "holdStatus": "held" }, { "id": "QP-113", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [], "units": [ "U-TDXdILA26" ], "asOf": "2026-10-21", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-21", "title": "미세한 폐 소견과 약제 위해의 연결", "question": "약제 투여 전의 미세한 폐 영상 소견이 이후 간질성 폐질환과 연관되면, 그 소견만으로 개인의 위해와 치료 선택을 정할 근거가 될까?", "judgment": "치료를 받은 한 코호트에서의 위해 연관성으로 기록한다. 미세한 소견도 무시할 수 없다는 연구 질문을 남기되 개인의 위험 확률이나 치료 배제·검사 전략의 이득으로 확대하는 판단은 보류한다. 모호한 소견과 확실한 소견의 차이가 유의하지 않았다는 결과도 두 집단의 동일함을 증명하지 않는다.", "basis": [ { "claim": "기저 폐 소견이 있는 집단에서 약제 관련 폐질환이 더 자주 관찰됐고 경쟁 사건을 고려한 분석에서도 연관됐다.", "units": [ "U-TDXdILA26" ] }, { "claim": "생존이나 소견 등급 사이의 유의한 차이는 확인되지 않았지만, 초록만으로 판독·위해 판정·중증도와 교란 통제를 충분히 확인할 수 없다.", "units": [ "U-TDXdILA26" ] } ], "objection": "영상 소견이 임상적으로 유용한 단서일 수 있다. 그러나 치료에 선택된 사람들의 관찰 위험을 개인의 절대 위험이나 특정 감시·배제 전략의 효과로 곧바로 옮길 수는 없다.", "changesMind": "판독과 위해 판정 방법을 감사하고 별도 자료에서 보정된 절대 위험과 불확실성을 재현하면 예측 범위를 갱신한다. 그에 따른 치료·감시 전략의 이득과 위해는 별도 비교가 필요하다.", "next": [ "영상 판독의 눈가림·일치도와 폐질환 판정 기준을 확인한다", "이전 치료와 숙주 요인·경쟁 사건의 처리를 대조한다", "관찰 연관성과 실제 감시·치료 변경 전략의 이득을 나눈다" ], "holdStatus": "held" }, { "id": "QP-114", "program": "breast", "targets": [ "CDK4/6" ], "biomarkers": [], "units": [ "U-EosinophilHR26" ], "asOf": "2026-10-21", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-21", "title": "호산구의 재발 연관성과 치료 선택 사이", "question": "수술 전 호산구 수가 낮은 재발 위험과 연관되고 약제 이득이 큰 집단을 구분했다고 보고돼도, 같은 지표로 치료 대상을 정할 수 있을까?", "judgment": "예후 연관성과 차등 치료 이득을 구분해 기록한다. 큰 확장 코호트와 가중 분석이 있어도 치료 배정·기점·문턱값·상호작용을 확인하기 전 선택 지표로서의 검증은 보류한다. 생쥐에서 호산구를 옮긴 결과를 사람의 혈구 수를 높여 재발을 막는 효과로 바꾸지 않는다.", "basis": [ { "claim": "저자들은 발견·확장 코호트의 재발 관련 연관성과 유전자 점수에 더한 예후 정보, 고위험 하위집단의 약제 이득을 보고했다. 하위집단을 모두 더해 독립 환자 수로 세지 않는다.", "units": [ "U-EosinophilHR26" ] }, { "claim": "초록에는 치료 배정과 고정 문턱값, 무작위 비교의 치료와 표지자 사이 상호작용 추정치가 없다. 조정과 가중만으로 그 빈칸을 채우지 않는다.", "units": [ "U-EosinophilHR26" ] } ], "objection": "면역 다중 측정과 동물 실험은 기전 가설을 보강하고 간단한 혈액 지표는 연구할 가치가 있다. 다만 기전의 개연성과 예후 정보가 어떤 치료의 상대적 이득을 미리 고르는 능력과 같지는 않다.", "changesMind": "원 방법에서 치료 배정·노출 시점·환자 중복·고정 기준과 상호작용을 확인하고, 별도 평가에서 치료별 이득과 위해를 검증하면 선택 능력의 적용 범위를 갱신한다.", "next": [ "고위험 치료 하위집단의 출처와 배정·기점을 확인한다", "문턱값의 선택과 치료별 상호작용 추정치를 대조한다", "예후 보정·치료 이득·혈구를 바꾸는 개입을 따로 평가한다" ], "holdStatus": "held" }, { "id": "QP-115", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-ACTOrganoid26" ], "asOf": "2026-10-21", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-21", "title": "배양 반응 점수를 환자 확률로 옮기지 않음", "question": "오가노이드의 성장 억제와 약물 노출을 합친 점수가 반응과 비슷한 구간을 만들면, 환자의 치료 성공확률이나 약제 생략의 안전성도 계산한 것일까?", "judgment": "약물별 취약성과 병용 기여를 나눠 보는 실험적 점수로 기록한다. 점수의 이름에 확률이 들어가도 사람의 결과에 맞춰 보정된 확률은 아니며, 시험관의 반응 유사 구간도 환자의 영상 반응이 아니다. 약제 구성 축소나 개인 선택의 안전성을 확정하는 해석은 보류한다.", "basis": [ { "claim": "완전한 측정이 있는 배양 표본에서 성분별 반응이 달랐고 병용 반응은 가장 활성이 큰 성분과 연관됐다. 전체 원 생검이나 임상 치료 결과를 평가한 것은 아니다.", "units": [ "U-ACTOrganoid26" ] }, { "claim": "점수는 성장률 반응과 혈장 노출을 합쳐 구성했으며 구간은 임상 반응 판정이 아니다. 공개 세포주에 적용한 계산도 독립 환자의 임상 검증이 아니다.", "units": [ "U-ACTOrganoid26" ] } ], "objection": "성분별 기여를 분해하면 다음 실험을 좁힐 수 있다. 다만 배양 성공과 완전 측정의 선택, 노출·대사·투여 순서가 다르면 점수의 크기를 환자의 이득이나 병용 상승작용으로 읽기 어렵다.", "changesMind": "원 입력·코드와 노출 조건을 대조해 고정한 점수를 재현하고, 독립 환자에서 사전에 정한 임상 결과와 보정·의사결정 이득을 검증하면 적용 범위를 갱신한다. 치료 축소의 안전성은 적절한 비교 연구가 필요하다.", "next": [ "배양·완전 측정 선택과 생물학적 반복을 확인한다", "약물·대사체 노출과 실제 투여 순서의 대응을 대조한다", "점수 재현과 독립 임상 예측·치료 축소 검증을 분리한다" ], "holdStatus": "held" }, { "id": "QP-116", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-QBS72S26" ], "asOf": "2026-10-21", "status": "판단 기록됨", "title": "실질 뇌전이와 연수막 신호를 나눠 읽음", "question": "같은 약제 시험에서 연수막 질환의 일부 영상 안정 신호와 실질 뇌전이의 반응 실패가 함께 보고되면 하나의 반응률이나 치료 성공으로 묶어도 될까?", "judgment": "같은 시험의 다른 코호트로 연결하고 질환 구획·평가변수·분모를 나눠 기록한다. 연수막 질환의 안정 또는 호전은 확인된 객관적 반응과 같지 않으며, 실질 뇌전이의 반응 실패를 다른 코호트의 분모에 옮기지 않는다. 뇌척수액에서 약물이 검출된 사실도 임상 이득이나 완치를 확정하지 않는다.", "basis": [ { "claim": "연수막 질환 논문과 계획서는 별도 코호트를 기술하며, 계획의 일차 반응 평가는 실질 뇌전이 집단에 배정돼 있다.", "units": [ "U-QBS72S26" ] }, { "claim": "새 등록 결과의 실질 뇌전이 단계에서는 완전·부분 반응이 없었다. 생존의 참가자 수 항목과 이상반응의 사건 수를 개월이나 고유 환자 수로 바꾸지 않는다.", "units": [ "U-QBS72S26" ] } ], "objection": "연수막 질환의 장기 안정 신호는 후속 연구를 설계할 단서다. 다만 작은 단일군의 선택된 경과나 다른 약제·환자군의 실패와의 간접 비교로 치료 우열을 정할 수는 없다.", "changesMind": "원 방법에서 코호트별 적격성·평가가능 분모·반응 확인·생존 단위·위해를 대조하고 적절한 별도 임상 평가에서 이득과 위해가 재현되면 해당 구획의 판단을 갱신한다.", "next": [ "논문과 등록 결과의 코호트·시점·평가변수를 대응시킨다", "참가자 수·기간·반응과 이상반응 사건 수를 각각 확인한다", "노출 검출·탐색 신호와 비교 임상 이득을 분리한다" ], "by": "Codex (GPT-6)", "added": "2026-10-21", "holdStatus": "held" }, { "id": "QP-117", "program": "colorectal", "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-PD1MaintenanceCRC26" ], "asOf": "2026-10-22", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-22", "title": "완전반응 뒤 유지 치료와 관찰의 간격", "question": "임상 완전반응 뒤 수술 없이 관찰한 집단과 면역치료를 더 받은 집단의 경과가 좋다면, 유지 치료나 수술의 생략이 안전하다고 판단할 수 있을까?", "judgment": "완전반응과 비수술 관리를 선택한 집단의 관찰 비교로 기록한다. 생존 차이를 뚜렷하게 찾지 못한 결과는 동등성이나 비열등성의 입증이 아니다. 반응 확인과 치료 시점·선택·추적 차이를 보존하며, 유지 치료나 수술을 생략하는 전략의 안전성과 완치 확대는 보류한다.", "basis": [ { "claim": "공식 출판사 원문에서 완전반응 뒤 관찰과 유지 치료의 경과 및 위해를 대조했다. 재성장에 대한 구제 치료와 병기·원발 부위가 섞인 선택 집단을 구분한다.", "units": [ "U-PD1MaintenanceCRC26" ] }, { "claim": "치료는 환자와 의사의 결정으로 정해졌다. 측정한 교란을 가중하고 치료 시점의 민감도 분석을 해도 사건이 드물고 무작위 배정이 아니라는 한계는 남는다.", "units": [ "U-PD1MaintenanceCRC26" ] } ], "objection": "불필요한 노출과 장기 위해를 줄이는 질문은 중요하다. 다만 완전반응 이전의 비반응자와 수술 집단을 제외한 결과, 결장과 직장의 다른 판정 기준, 구제 치료 가능성을 모든 환자의 생략 전략으로 옮기기는 어렵다.", "changesMind": "고정한 반응 판정과 치료 기점·추적 계획을 적용한 전향적 비교에서 원발 부위별 재성장·원격 재발·구제 실패와 위해의 불확실성이 충분히 좁아지면 생략 전략의 적용 범위를 갱신한다.", "next": [ "수신한 원문의 선택 흐름과 반응 판정·노출 시점을 고정해 대조한다", "보충 자료와 독립 전향 연구에서 재성장·구제 실패 및 위해를 확인한다", "임상 완전반응과 병리 완전반응·장기 재발 부재·완치를 구분한다" ], "holdStatus": "held" }, { "id": "QP-118", "program": "gastric", "targets": [], "biomarkers": [], "units": [ "U-FABP4Peritoneal26" ], "asOf": "2026-10-22", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-22", "title": "복막 전이의 지방 이용을 끊는 가설", "question": "지방세포가 공급한 지방산을 이용하고 산화를 막는 경로가 위암 복막 전이에 연결되면, 그 경로를 억제하는 치료 후보를 어떻게 좁혀야 할까?", "judgment": "지방 이용과 세포 사멸 회피를 잇는 기전 가설로 기록한다. 환자 조직의 발현과 실험 모델의 경로 조작을 사람의 전이 치료 효과로 확대하지 않는다. 표적 특이성·구제 실험·노출·위해를 원 방법에서 확인하기 전 약제나 임상 효능의 순위를 정하는 판단은 보류한다.", "basis": [ { "claim": "저자들은 지방세포 신호에 따른 단백질 발현과 지방산 유입, 산화 억제·단백질 분해를 연결하는 경로를 보고했다.", "units": [ "U-FABP4Peritoneal26" ] }, { "claim": "현재 받은 초록은 기전의 방향을 설명하지만 모델 구성·독립 반복·약물 노출·위해와 이미 형성된 전이에 대한 치료 검증은 확인하지 못했다.", "units": [ "U-FABP4Peritoneal26" ] } ], "objection": "대사 의존성을 끊는 접근이 유망할 수 있다. 그러나 유전적 조작과 실제 약제는 다르고, 전이 형성의 억제와 이미 생긴 전이의 치료도 다른 문제다. 정상 지방 대사에 대한 영향까지 확인해야 한다.", "changesMind": "원 방법과 구제 실험에서 경로 특이성을 확인하고, 별도 모델에서 도달 가능한 약물 노출로 형성된 전이의 부담과 위해를 재현하면 다음 실험 후보의 범위를 갱신한다. 사람의 이득은 별도 임상 검증이 필요하다.", "next": [ "모델과 원 조직의 출처·반복·배정 및 눈가림을 확인한다", "지방 유입·산화·세포 사멸과 전이 부담의 평가변수를 분리한다", "유전 조작의 기전 확인과 약물 노출·정상 조직 위해 검증을 나눈다" ], "holdStatus": "held" }, { "id": "QP-119", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B", "BM-HER2LOW-B" ], "units": [ "U-HER2ResidualDiscord26" ], "asOf": "2026-10-23", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-23", "title": "잔존 병변의 HER2 불일치를 읽는 범위", "question": "수술 전 치료 뒤 남은 병변에서 HER2 0이 저발현으로 바뀌고 재발 관련 경과와 연관되면, 그 변화로 새 약제의 이득까지 판단할 수 있을까?", "judgment": "잔존 병변을 가진 환자에서의 분류 변화와 예후 연관성으로 기록한다. 생검과 수술 검체의 차이를 치료가 일으킨 생물학적 변화로 단정하지 않고, 선택된 재판독·표본 구성·판독 변동을 함께 살핀다. 재검사에 따라 약제를 정하는 전략의 이득이나 전이암 결과의 이식은 보류한다.", "basis": [ { "claim": "수술 전후 쌍을 비교한 집단은 잔존 병변이 있는 환자에 한정되며 완전반응자는 빠져 있다. 원문에서 처음 불일치로 보고된 사례는 재검토했으나 일치 사례를 모두 다시 판독하지는 않았다.", "units": [ "U-HER2ResidualDiscord26" ] }, { "claim": "전체 저발현 집단의 반응 차이는 호르몬 수용체별로 나눈 분석에서 유의하지 않았다. 분류 불일치의 예후 연관성은 보고됐지만 재검사 기반 약제 배정의 임상 이득을 비교한 연구는 아니다.", "units": [ "U-HER2ResidualDiscord26" ] } ], "objection": "잔존 병변의 재평가는 새로운 연구 집단을 찾는 데 도움이 될 수 있다. 다만 발현의 공간적 이질성과 채취·고정·판독 차이를 생물학적 전환과 분리해야 하며, 비유의를 두 집단의 동등성으로 읽어서는 안 된다.", "changesMind": "처음 일치한 사례까지 포함한 표준화·눈가림 재판독에서 변화가 재현되고, 고정한 잔존 질환 집단의 전향적 비교에서 재평가에 따른 치료의 이득과 위해가 확인되면 적용 범위를 갱신한다.", "next": [ "일치·불일치 양쪽의 검체 채취와 판독 재현성을 비교한다", "반응으로 선택된 집단과 평가 기점·예후 모형의 선택 절차를 대조한다", "HER2 0·저발현·초저발현 분류와 잔존 병변의 약제 이득을 따로 검증한다" ], "holdStatus": "held" }, { "id": "QP-120", "program": "breast", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-INTEGRAL26" ], "asOf": "2026-10-24", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-24", "title": "국소 면역 자극의 중단을 기록하는 기준", "question": "종양 안의 면역 자극이 생쥐에서는 효과를 보였지만 사람의 작은 병용 시험이 독성으로 중단됐다면, 다음 연구에서 어떤 경계를 유지해야 할까?", "judgment": "이 병용·투여 조건에서 관찰된 위해와 조기 종료를 실패 근거로 보존한다. 이를 용량 조절이 안전하다는 근거나 면역 경로 전체의 무효로 바꾸지 않는다. 특정 성분의 인과 기여와 다른 전달 방식의 이득은 구분해 보류한다.", "basis": [ { "claim": "초록과 등록은 작은 단일군 시험의 조기 종료와 제한된 반응을 보고한다. 원문에는 이전 면역치료·추가 약제·용량 변경과 사망 귀속의 불확실성이 있다.", "units": [ "U-INTEGRAL26" ] }, { "claim": "본문의 반응 백분율은 초록·분모와 맞지 않고 등록의 병리 반응 제목에는 영상 반응 설명이 붙어 있다. 이를 임의로 통일하거나 완전한 평가변수 검증으로 표시하지 않는다.", "units": [ "U-INTEGRAL26" ] } ], "objection": "종양 내 투여나 면역 활성 신호가 전신 노출을 줄이는 가설을 지지할 수는 있다. 그러나 작은 비무작위 용량 집단이나 반응자 한 명의 면역 변화로 안전한 전달 방식과 예측 지표가 검증된 것은 아니다.", "changesMind": "원 프로토콜과 정정에서 평가변수·분모·투약 변경과 위해 판정이 정리되고, 별도 연구에서 노출·전달·정상 조직 위해를 사전에 정한 기준으로 검증하면 다음 후보 범위를 갱신한다. 현재 시험의 실패 기록은 보존한다.", "next": [ "원 프로토콜에서 병리·영상 반응과 중단 시점의 분모를 대조한다", "병용 약제·감염·진행과 개별 성분의 위해 귀속을 구분한다", "면역 활성·종양 반응·장기 생존과 안전한 전달 검증을 분리한다" ], "holdStatus": "held" }, { "id": "QP-121", "program": "colorectal", "targets": [ "PDCD1" ], "biomarkers": [ "BM-MSI-C" ], "units": [ "U-NICHE2" ], "asOf": "2026-10-24", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-10-24", "title": "수술을 포함한 무재발과 완치의 경계", "question": "짧은 수술 전 면역치료와 수술을 거친 집단에서 장기 무병생존과 전체 생존이 높게 보고되면, 완치나 수술 생략까지 같은 결과로 인정할 수 있을까?", "judgment": "같은 시험의 성숙한 추적을 기존 근거에 연결해 무병생존 미확인이라는 옛 한계를 갱신한다. 동시에 수술을 포함한 전략·계획 준수 집단·서로 다른 평가 기점과 탐색적 전체 생존을 보존한다. 관찰 기간에 사건이 없다는 결과를 영구적인 재발 위험 소멸이나 수술 생략의 검증으로 확대하는 판단은 보류한다.", "basis": [ { "claim": "후속 논문은 수술 뒤 무병생존을 일차 효능 평가변수로 보고하고 등록 시점부터의 전체 생존은 탐색적 사후 분석으로 제시했다. 이전 병리 반응 논문과 같은 시험이며 독립 반복이 아니다.", "units": [ "U-NICHE2" ] }, { "claim": "분석은 계획 준수 집단이며 혈중 종양 유전자 검사는 시점별 수신 가능한 표본에 한정된다. 수술 뒤 음성 소견이나 사건 없는 생존 곡선으로 치료 생략 전략의 효과를 대신하지 않는다.", "units": [ "U-NICHE2" ] } ], "objection": "긴 추적에서 재발이나 사망이 관찰되지 않은 것은 초기 병리 반응보다 직접적인 임상 정보다. 다만 모든 사람이 같은 기간 추적된 것은 아니고, 비교군 부재·선별·중도절단과 추정의 불확실성이 사라지지는 않는다.", "changesMind": "추적 대상·위험집단 수·중도절단·확률 구간 계산과 프로토콜을 확인해 장기 판단을 갱신한다. 수술이나 추가 처치를 생략하는 전략은 그에 맞는 전향적 비교와 구제 실패·위해 확인이 있어야 별도로 평가한다.", "next": [ "수술과 등록의 서로 다른 기점 및 계획 준수 분석의 제외를 대조한다", "사건 없는 생존 추정의 위험집단 수·중도절단·구간 계산을 확인한다", "혈중 검사 표본 분모와 검사에 따라 처치를 바꾸는 이득을 구분한다" ], "holdStatus": "held" }, { "id": "QP-122", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-FIRE3", "U-CALGB80405", "U-PARADIGM" ], "asOf": "2026-10-30", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-30", "title": "일차 항EGFR 항체의 생존 이득은 시험마다 다르다", "question": "RAS 또는 KRAS 야생형 전이성 대장암의 일차 치료에서 항EGFR 항체가 베바시주맙보다 생존을 늘린다고 말할 수 있는가?", "judgment": "일반적으로는 말하지 않는다. 독일·오스트리아 시험은 일차 평가변수인 반응률에서 차이가 없었지만 생존이 길었고, 북미 시험은 일차 평가변수인 생존에서 차이를 보이지 못했다. 좌측 종양만 미리 정해 본 일본 시험에서는 생존이 길었다. 종양 위치와 RAS 검사 범위가 시험마다 달라, 모든 야생형 환자에서의 우위는 보류하고 좌측 종양에 한한 결과로 기록한다.", "basis": [ { "claim": "KRAS 엑손 2 야생형 592명에서 반응률은 62.0% 대 58.0%로 차이가 없었고, 생존 중앙값은 28.7개월 대 25.0개월(위험비 0.77)이었다.", "units": [ "U-FIRE3" ] }, { "claim": "KRAS 야생형 1137명에서 생존 중앙값은 30.0개월 대 29.0개월(위험비 0.88, P=.08)로 차이를 보이지 못했다.", "units": [ "U-CALGB80405" ] }, { "claim": "RAS 야생형 좌측 종양에서 생존 중앙값은 37.9개월 대 34.3개월(위험비 0.82)이었다.", "units": [ "U-PARADIGM" ] } ], "objection": "세 시험 모두 위험비가 항EGFR 쪽에 있고 좌측 종양이 대부분이었으므로, 야생형 대장암 전체에서 항EGFR이 낫다고 보는 견해가 있다.", "changesMind": "세 시험의 RAS 확장 검사와 종양 위치별 개별 환자 자료 분석이 공개되면 범위를 다시 쓴다.", "next": [ "두 서양 시험의 RAS 확장 검사·종양 위치 하위 분석을 원문으로 확인한다", "이후 치료 차이가 생존 차이에 기여한 정도를 확인한다" ], "holdStatus": "held" }, { "id": "QP-123", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-TRIPLETE", "U-JCOG0603", "U-IDEA18" ], "asOf": "2026-10-30", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-30", "title": "강화 요법이 늘린 지표와 생존은 따로 본다", "question": "전이성 대장암에서 항암을 더하거나 강화한 치료가 일부 지표를 개선했을 때 생존 이득으로 읽을 수 있는가?", "judgment": "읽지 않는다. 간 전이 절제 뒤 보조 항암은 무병 생존을 늘렸지만 5년 생존은 절제만 한 군보다 수치상 낮았다. 일차 3제 강화 항암은 반응률을 높이지 못했다. 각 시험이 개선한 지표만 기록하고 생존 이득은 따로 확인될 때까지 보류한다.", "basis": [ { "claim": "300명을 배정한 시험에서 5년 무병 생존은 49.8% 대 38.7%(위험비 0.67)였으나, 5년 생존은 71.2% 대 83.1%로 보조 항암군이 낮았다.", "units": [ "U-JCOG0603" ] }, { "claim": "435명에서 반응률은 73% 대 76%(승산비 0.87)로 늘지 않았고, 무진행 생존도 12.7개월 대 12.3개월로 차이가 없었다.", "units": [ "U-TRIPLETE" ] }, { "claim": "3기 결장암 보조 항암 기간 비교에서도 전체 집단의 비열등성은 확인되지 않았고, 그 분석의 초록에는 전체 생존 결과가 없다.", "units": [ "U-IDEA18" ] } ], "objection": "무병 생존 개선은 재발을 늦춘 실제 이득이고 생존 차이는 이후 치료의 영향일 수 있으므로, 보조 항암의 가치는 이미 충분하다는 견해가 있다.", "changesMind": "간 전이 절제 뒤 보조 항암의 생존을 다시 본 장기 추적이나 다른 무작위 시험 결과가 공개되면 다시 판단한다.", "next": [ "JCOG0603 원문에서 재발 뒤 치료와 사망 원인을 확인한다", "간 전이 절제 뒤 보조 항암의 다른 무작위 시험을 찾는다" ], "holdStatus": "held" }, { "id": "QP-124", "program": "thyroid", "targets": [], "biomarkers": [], "units": [ "U-T-DABTHY", "U-T-ROAR" ], "asOf": "2026-10-30", "status": "판단 기록됨", "by": "Claude", "added": "2026-10-30", "title": "분화암에서 MEK 억제제 추가 이득은 미확인", "question": "방사성요오드 불응 BRAF 변이 분화 갑상선암에서 다브라페닙에 트라메티닙을 더하면 효과가 커진다고 볼 수 있는가?", "judgment": "볼 수 없다. 두 치료를 무작위로 비교한 2상에서 24주 반응률 차이가 없었다. 역형성암의 병용 효과는 대조군 없는 코호트에서 나온 것이라 분화암으로 옮기지 않는다. 병용의 추가 이득은 보류한다.", "basis": [ { "claim": "53명을 배정한 2상에서 수정 기준 반응률은 단독 42%(11/26), 병용 48%(13/27)였고(p=0.67), 표준 기준 반응률은 35% 대 30%였다.", "units": [ "U-T-DABTHY" ] }, { "claim": "치료 관련 사망은 없었다. 반응은 24주 안에 평가했고, 초록은 무진행 생존을 보고하지 않았다.", "units": [ "U-T-DABTHY" ] }, { "claim": "역형성암 36명의 병용 코호트에서 반응률 56%가 보고됐으나 대조군이 없다.", "units": [ "U-T-ROAR" ] } ], "objection": "다른 BRAF 변이암에서 병용이 단독보다 나았던 경험이 있으므로 작은 2상의 무차이는 검정력 부족일 뿐이라는 견해가 있다.", "changesMind": "더 큰 무작위 비교나 무진행 생존을 비교한 결과가 공개되면 다시 판단한다.", "next": [ "2상 원문에서 무진행 생존과 교차 투여를 확인한다", "분화암 대상 병용 시험의 등록 정보를 찾는다" ], "holdStatus": "held" }, { "id": "QP-130", "program": "breast", "targets": [], "biomarkers": [], "units": [ "U-NabDDHR26" ], "asOf": "2026-11-12", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-11-12", "title": "잔존 종양 부담 지표가 보여주는 범위", "question": "잔존 종양 부담이 줄어든 수술 전 항암요법을 생존 이득이 확인된 치료로 볼 수 있는가?", "judgment": "잔존 종양 부담의 개선은 받아들이되 생존 우월성·동등성이나 완치로 확대하지 않는다. 중증 감각신경병증 신호와 논문·등록 간 불일치를 함께 남기고 치료 선택 판단은 유보한다.", "objection": "생존 차이가 유의하지 않다는 사실만으로 효과가 없다고 단정할 수도 없다. 추적·사건 수·검정 계획과 위해의 지속성을 확인해야 한다.", "changesMind": "사전 계획과 개정 이력으로 등록 차이가 설명되고 생존 분석의 방향·정밀도 및 신경독성의 빈도·회복 경과가 확인되면 판단을 갱신한다.", "basis": [ { "claim": "같은 무작위시험에서 잔존 종양 부담 지표는 개선됐지만 병리학적 완전반응과 생존 비교의 우월성은 확인되지 않았다.", "units": [ "U-NabDDHR26" ] }, { "claim": "전체 중증 이상반응 비율만으로 개별 독성의 차이를 지울 수 없다. 중증 감각신경병증은 시험군에서만 보고됐다.", "units": [ "U-NabDDHR26" ] } ], "next": [ "원 프로토콜과 개정본에서 모집 수·시험 단계·등록일의 차이를 대조한다", "생존 분석의 기준군과 신경병증 평가 집단·지속 기간을 원문 표에서 확인한다" ], "holdStatus": "held" }, { "id": "QP-131", "program": "colorectal", "targets": [], "biomarkers": [], "units": [ "U-CRPMctDNA26" ], "asOf": "2026-11-12", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-11-12", "title": "복막 전이의 잔존 신호를 읽는 조건", "question": "복막 전이 절제 뒤 혈중 종양 디엔에이 양성과 재발의 연관성을 치료 강화의 근거로 옮길 수 있는가?", "judgment": "수술받고 채혈 자료가 있는 집단의 예후 연관성으로 기록한다. 검사 음성의 질환 배제, 신호 소실의 치료 효과, 검사 기반 수술 시점이나 치료 강화의 이득은 유보한다.", "objection": "관찰된 연관성은 후속 연구의 출발점이지만 채혈 시점·검사 선택·추적 강도와 기존 임상 요인의 영향을 분리하지 못했다.", "changesMind": "같은 채혈 기준과 분석 기점을 적용한 독립 자료에서 재현하고, 검사에 따른 개입을 비교한 연구에서 위해를 포함한 결과 개선을 확인하면 판단을 갱신한다.", "basis": [ { "claim": "수술 후 양성은 짧은 무재발 생존과 연관됐으나 시점별 분석 인원이 다르므로 전체 집단의 짝지은 신호 소실률로 바꾸지 않는다.", "units": [ "U-CRPMctDNA26" ] }, { "claim": "원문 분석은 단변량이며 생존 기점은 수술일이다. 이후 채혈로 분류한 집단의 시간 편향과 검사 확보에 따른 선택을 점검해야 한다.", "units": [ "U-CRPMctDNA26" ] } ], "next": [ "채혈 시점과 사건·중도절단 시점을 맞춘 분석 계획을 비교한다", "기존 코호트와 환자 중복을 확인하고 검사 기반 개입 연구의 결과 공개를 별도로 감시한다" ], "holdStatus": "held" }, { "id": "QP-132", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-HER2CR26" ], "asOf": "2026-11-13", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-11-13", "title": "오래 반응한 유방암에서 음성 검사의 범위", "question": "허투 표적치료에 오래 반응한 전이성 유방암에서 종양 디엔에이가 계속 음성이면 치료를 줄여도 되는가?", "judgment": "장기 반응군에서 채혈 시점별 음성이 얼마나 흔했는지 기록한다. 계속 음성이었던 환자도 마지막 채혈 뒤 진행했다. 검사 결과를 기준으로 치료 용량을 줄이거나 치료를 중단하는 전략은 이 연구에서 평가하지 않았다.", "basis": [ { "claim": "같은 환자의 여러 검체와 환자별 반복 음성을 따로 읽는다. 검사를 평가할 수 있었던 환자는 등록 집단의 일부다.", "units": [ "U-HER2CR26" ] }, { "claim": "계속 음성이었던 환자도 마지막 채혈 이후 진행했다. 이 사례는 채혈 사이의 경과를 알 수 없다는 한계를 보여 준다.", "units": [ "U-HER2CR26" ] } ], "objection": "이미 오래 반응한 사람을 모집했고 치료 지속과 중단을 무작위로 비교하지 않았다. 짧은 등록 후 추적으로 늦은 재발 위험을 확정할 수 없다.", "changesMind": "같은 검사 일정과 영상 기준으로 치료 지속과 축소를 비교하고 장기 진행과 위해를 평가한 결과가 공개되면 판단을 갱신한다.", "next": [ "모집 전 반응 기간과 등록 뒤 추적 기간을 구분하고 채혈 간격과 빠진 검체를 확인한다" ], "holdStatus": "held" }, { "id": "QP-133", "program": "colorectal", "targets": [ "PDCD1" ], "biomarkers": [], "units": [ "U-CA2098M4" ], "asOf": "2026-11-13", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-11-13", "title": "수술 병리와 비수술 추적을 합친 반응률", "question": "직장암에서 수술 병리와 비수술 추적의 완전반응을 합한 지표로 면역치료를 추가한 이득을 판단할 수 있는가?", "judgment": "수술한 집단의 병리학적 반응과 수술하지 않은 집단의 지속된 임상 반응을 각각 남긴다. 단일군 결과에서 면역치료의 추가 이득과 수술을 줄이는 전략의 효과는 보류한다.", "basis": [ { "claim": "수술한 환자와 수술하지 않은 환자에게 다른 기준과 시점을 적용했다. 전체 합성 지표를 수술 환자의 병리학적 완전반응률로 해석할 수 없다.", "units": [ "U-CA2098M4" ] }, { "claim": "병용치료 기간에 중증 이상반응과 사망이 보고됐다. 사망의 원인과 면역치료가 더해진 위해의 크기는 확정되지 않았다.", "units": [ "U-CA2098M4" ] } ], "objection": "수술을 피하면서 반응을 오래 유지하는지는 중요한 질문이다. 비교군 없이 수술 선택과 추적 기간이 다른 두 집단의 결과를 더하면 치료 효과가 얼마나 달라졌는지 알기 어렵다.", "changesMind": "같은 항암과 방사선치료를 비교군에 적용한 무작위시험에서 장기 직장 보존, 재발, 중증 위해를 함께 보고하면 판단을 갱신한다.", "next": [ "각 반응의 분모와 관찰 기점, 수술 선택 기준, 사망 사례의 평가 방법을 확인한다" ], "holdStatus": "held" }, { "id": "QP-134", "program": "breast", "targets": [ "ERBB2" ], "biomarkers": [ "BM-HER2-B" ], "units": [ "U-UCI1467" ], "asOf": "2026-11-13", "status": "판단 기록됨", "by": "Codex (GPT-6)", "added": "2026-11-13", "title": "허투에 따라 나뉜 치료군의 비교 한계", "question": "허투 양성과 음성에 서로 다른 약제를 배정한 수술 전 연구에서 두 군의 무진행생존 차이로 약제의 효과를 비교할 수 있는가?", "judgment": "각 허투 집단에서 보고된 무진행생존 추정치만 기록한다. 환자 특성과 추가 약제가 함께 달라 약제 간 비교와 허투 상태에 따른 치료 효과 차이는 보류한다.", "basis": [ { "claim": "배정 기준은 허투 상태였다. 무진행생존의 평가 집단과 등록 집단은 인원이 다르고 완전반응의 수치 결과는 게시되지 않았다.", "units": [ "U-UCI1467" ] } ], "objection": "각 군의 경과는 후속 비교를 설계할 때 참고가 된다. 등록 자료만으로 치료 배정과 환자 특성의 영향을 분리할 수 없다.", "changesMind": "같은 허투 상태와 치료 조건에서 비교약을 무작위 배정하고 사건 수와 추적 기간을 공개하면 치료 효과를 다시 판단한다.", "next": [ "평가에서 빠진 환자의 이유와 완전반응의 후속 게시를 확인한다" ], "holdStatus": "held" } ], "briefs": [ { "id": "RB-01", "program": "gxb", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6)", "title": "HER2 across cancers: shared target, different evidence", "summary": "A common target can support a research question across gastric and breast cancer. The treatment effect still belongs to the trial population, treatment setting and comparator that established it.", "scope": "Narrative synthesis of selected library records on HER2-directed treatment. It is not a systematic review or a treatment sequence recommendation.", "units": [ "U-ToGA", "U-GATSBY", "U-JACOB", "U-EGF100151", "U-DG02", "U-DG04", "U-KATHERINE", "U-DB05", "U-HER2Residual26" ], "pairs": [ "QP-01", "QP-06", "QP-28", "QP-32" ], "sections": [ { "heading": "What can travel with the target", "paragraphs": [ "HER2 is a useful shared starting point for gastric and breast cancer research. It supplies a molecular target and a way to ask whether a drug reaches or affects selected tumours. It does not make the clinical populations interchangeable. Tumour site, how HER2 was scored, prior treatment and the treatment setting remain part of the evidence.", "ToGA provides a gastric comparison for trastuzumab with chemotherapy. The gastric GATSBY and JACOB studies test different additions or treatment formats in their own settings. Their outcomes limit the inference that an agent or combination that works in breast cancer will reproduce that benefit in gastric cancer. A negative result limits the tested strategy; it does not erase every possible use of the target." ], "units": [ "U-ToGA", "U-GATSBY", "U-JACOB" ] }, { "heading": "A drug-class label is too coarse for the comparison", "paragraphs": [ "The updated EGF100151 record distinguishes the initial time-to-progression result from the later overall-survival analysis in previously treated HER2-positive advanced breast cancer. It is a comparison of lapatinib plus capecitabine with capecitabine under that trial design. It is not a direct comparison with a gastric HER2 strategy or with a current first-line breast regimen.", "Likewise, trastuzumab emtansine and trastuzumab deruxtecan should not be treated as interchangeable observations merely because both are antibody-drug conjugates. GATSBY and DESTINY-Gastric04 answer different comparisons. Their results justify keeping delivery format, eligibility, line of treatment and comparator visible rather than assigning an effect to the whole class." ], "units": [ "U-EGF100151", "U-GATSBY", "U-DG04" ] }, { "heading": "The time of HER2 measurement changes who enters the evidence", "paragraphs": [ "DESTINY-Gastric02 required confirmation of HER2-positive disease in a biopsy after progression. Its single-arm response result therefore belongs to a reselected population. A study selected only from an earlier specimen may represent a different group even when both are described as HER2-positive.", "The residual-breast-cancer observational record describes a selected subset with sufficient residual invasive tissue for reassessment. A change in that tissue classification is an observation about assessable specimens. It does not, by itself, establish acquired functional resistance or show that changing postoperative treatment improves outcomes. Sampling, assay variation and biological change need separate consideration." ], "units": [ "U-DG02", "U-HER2Residual26" ] }, { "heading": "Residual early breast cancer adds a separate comparison", "paragraphs": [ "KATHERINE supplies randomized evidence in patients with residual invasive HER2-positive breast cancer after neoadjuvant treatment. Its long-term follow-up must remain attached to the original trial rather than being counted as a separate independent study.", "DESTINY-Breast05 adds a direct comparison of trastuzumab deruxtecan with trastuzumab emtansine in its selected high-risk residual-disease population. Its disease-free survival findings and interstitial lung disease findings belong together. Neither the setting nor the eligibility matches every patient in KATHERINE, every patient with residual disease, or metastatic gastric cancer. An indirect ranking of their reported effect sizes would discard those distinctions." ], "units": [ "U-KATHERINE", "U-DB05" ] }, { "heading": "The research judgment this supports", "paragraphs": [ "Transfer the molecular question, then rebuild the clinical claim in the receiving cancer and setting. Keep post-treatment target status, treatment format and the actual comparator attached to each result. Where a matched comparison is missing, preserve an open question rather than inferring an optimal sequence.", "A tissue-change report can nominate a subgroup question. A randomized treatment comparison can estimate a treatment effect in its enrolled population. Connecting the two requires compatible specimens, definitions and analyses; placing the papers next to one another is not itself that validation." ], "units": [ "U-HER2Residual26", "U-DG04", "U-KATHERINE", "U-DB05" ] } ], "comparison": [ { "units": [ "U-DG02" ], "context": "Advanced gastric cancer; HER2 reassessed after progression", "reads": "Activity in a selected single-arm cohort", "boundary": "No randomized comparator; do not generalize the selected population to all previously HER2-positive disease." }, { "units": [ "U-DG04" ], "context": "Advanced gastric cancer after trastuzumab-based treatment", "reads": "Direct comparison with ramucirumab plus paclitaxel", "boundary": "A gastric treatment comparison, not evidence for an entire ADC class across cancers." }, { "units": [ "U-KATHERINE", "U-DB05" ], "context": "Residual invasive early breast cancer after neoadjuvant treatment", "reads": "Randomized postoperative strategies with distinct eligibility and follow-up", "boundary": "Retain adverse events and eligibility; do not rank separate trials by their hazard ratios." }, { "units": [ "U-HER2Residual26" ], "context": "Assessable residual breast-tumour specimens", "reads": "Observed change in HER2 classification", "boundary": "A biomarker observation does not establish the benefit of a treatment change." } ], "changesMind": "Matched, prospectively specified comparisons that connect repeat HER2 assessment to treatment outcomes would strengthen the proposed links. A new response report alone would not establish a cross-cancer treatment effect.", "next": [ "Review paired-specimen subgroup reports with their original trial, assay and assessable denominator.", "Update adverse-event and follow-up information alongside each efficacy update.", "Keep any sequencing claim open until directly relevant comparative evidence is curated." ] }, { "id": "RB-02", "program": "gxb", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6), original synthesis; additions by Gemini Flash3.8, reviewed by Muse Spark1.3, integrated by Codex (GPT-6)", "title": "When follow-up changes the endpoint story", "summary": "An identifier checked today can still point to an early result. This brief distinguishes an initial response finding, later time-to-event analyses and a mature overall-survival test.", "scope": "Focused narrative comparison of updated gastric and breast trial records. Endpoint definitions and analysis populations remain study-specific.", "units": [ "U-KN522", "U-monarchE", "U-TROPIONB01", "U-CLASSIC", "U-JAVG100", "U-MATTERHORN", "U-EGF100151", "U-KN811", "U-OlympiAD" ], "pairs": [ "QP-20", "QP-29", "QP-30", "QP-31" ], "sections": [ { "heading": "A later paper can change what may be concluded", "paragraphs": [ "A study record should identify which analysis supports its headline. Pathological response, invasive disease-free survival, progression-free survival and overall survival measure different outcomes. Refreshing a registry status or a publication identifier does not update the clinical conclusion unless the later analysis is read and incorporated.", "For KEYNOTE-522, the library now connects the initial pathological response report, event-free survival and the final overall-survival analysis within one evidence unit. The later survival report adds an outcome that the early response analysis could not establish on its own. It does not turn every pathological complete response into proof of cure." ], "units": [ "U-KN522" ] }, { "heading": "Longer follow-up can support a stronger, still bounded statement", "paragraphs": [ "The updated monarchE record links its initial recurrence findings to the later overall-survival analysis. That additional evidence concerns the enrolled high-risk, node-positive hormone-receptor-positive, HER2-negative early breast cancer population. It should not silently enlarge the eligibility or demonstrate equal benefit for other drugs in the same class.", "CLASSIC connects an earlier disease-free survival analysis with longer follow-up after curative D2 gastrectomy. Its postoperative strategy is not the same intervention as the whole perioperative strategy in MATTERHORN. Both are relevant to recurrence research, but their populations, treatment phases and comparators cannot be dropped from the interpretation." ], "units": [ "U-monarchE", "U-CLASSIC", "U-MATTERHORN" ] }, { "heading": "Progression and overall survival can yield different conclusions", "paragraphs": [ "TROPION-Breast01 retains its progression-free survival result while adding the final overall-survival analysis, which did not establish a statistically significant improvement. Calling the entire study simply positive would hide that difference. Calling every possible effect absent would also go beyond what the analysis established.", "Subsequent therapies were imbalanced in the reported overall-survival analysis. That is a possible influence on the observed contrast, not proof that an otherwise hidden survival benefit exists. A proposed explanation needs its own assumptions and analysis; it cannot replace the trial result.", "EGF100151 similarly requires the initial progression endpoint and the later survival analysis to be read separately. Changes to trial conduct and post-randomization treatment are part of the uncertainty rather than a licence to choose whichever estimate appears most favorable.", "In OlympiAD, olaparib was compared with physician-choice single-agent chemotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer. Although blinded independent central review confirmed a statistically significant intention-to-treat progression-free survival benefit, the planned final prespecified overall-survival analysis did not show a statistically significant improvement. Subsequent post-hoc extended follow-up reported consistent survival findings, but post-hoc analysis cannot transform statistical non-significance into proof of equivalence or substitute for independent prospective replication. Furthermore, favorable estimates in the exploratory first-line subgroup provide hypothesis generation rather than definitive whole-population survival evidence. Distinct from the adjuvant OlympiA trial in early-stage disease, OlympiAD remains bounded to metastatic cancer, where primary progression gains cannot be presumed to confer overall survival extension." ], "units": [ "U-TROPIONB01", "U-EGF100151", "U-OlympiAD" ] }, { "heading": "The treatment phase must survive the summary", "paragraphs": [ "JAVELIN Gastric 100 randomized a maintenance strategy after induction treatment. It does not answer whether the same agent would add benefit at every phase of gastric cancer treatment. Its negative primary comparison belongs in the evidence library with the selection step that preceded randomization.", "MATTERHORN and KEYNOTE-522 evaluate strategies spanning treatment before and after surgery. Even when the randomized strategy improves a survival endpoint, that comparison does not isolate the contribution of the preoperative phase, the postoperative phase, or the interaction between them. A phase-specific conclusion would require a design or analysis that identifies that contribution." ], "units": [ "U-JAVG100", "U-MATTERHORN", "U-KN522" ] }, { "heading": "Early response and progression findings mature into bounded survival evidence", "paragraphs": [ "In KEYNOTE-811, an initial objective response readout and subsequent interim progression-free survival findings preceded the final overall-survival analysis within one randomized trial. The resulting survival benefit applies to the randomized first-line regimen of pembrolizumab combined with trastuzumab and chemotherapy against placebo plus trastuzumab and platinum-fluoropyrimidine chemotherapy in unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma, rather than HER2-negative disease, later treatment lines, or other cancers, and it cannot be construed as cure. In addition, findings in the full randomized population must be distinguished from exploratory PD-L1 combined positive score (CPS) subsets: tumors with CPS of 1 or greater showed a favorable survival estimate, whereas the small CPS-less-than-1 stratum yielded a wide interval that establishes neither harm, absence of effect, nor equivalence, and should not be cited as standalone predictive validation.", "The original correspondence reporting final overall survival has no PubMed abstract. The library therefore links the original report and the FDA-authored review that summarizes the final survival analysis. These sequential reports strengthen the account of the same trial; they are not independent replication, and a final survival result does not erase uncertainty about subgroup effects." ], "units": [ "U-KN811" ] }, { "heading": "How the library should record an update", "paragraphs": [ "Keep the trial identity stable and attach the later papers to it. Name the outcome, analysis timing, comparator and remaining uncertainty. Preserve earlier reports as part of the same study history. The number of papers can rise while the number of independent trials stays unchanged.", "A mature overall-survival result may resolve one uncertainty while leaving others open: subgroup applicability, late toxicity, treatment sequencing and the separate contribution of treatment phases. The judgment should change only as far as the new evidence reaches." ], "units": [ "U-KN522", "U-monarchE", "U-TROPIONB01", "U-MATTERHORN" ] } ], "comparison": [ { "units": [ "U-KN522", "U-monarchE" ], "context": "Selected early breast cancer populations", "reads": "Later overall-survival results extend earlier outcome reports", "boundary": "Follow-up strengthens the same trial; it is not independent replication or evidence for broader eligibility." }, { "units": [ "U-TROPIONB01", "U-EGF100151" ], "context": "Previously treated advanced breast cancer", "reads": "Progression endpoints and overall-survival analyses must be separated", "boundary": "A non-significant survival test is neither demonstrated equivalence nor proof of a hidden benefit." }, { "units": [ "U-CLASSIC", "U-MATTERHORN" ], "context": "Postoperative and perioperative gastric strategies", "reads": "Each randomized strategy has its own comparator and treatment phases", "boundary": "Do not infer the contribution of a single phase from the whole strategy." }, { "units": [ "U-JAVG100" ], "context": "Maintenance after induction for advanced gastric or junctional cancer", "reads": "A negative maintenance comparison", "boundary": "It does not establish failure of every use of the agent or target." }, { "units": [ "U-KN811" ], "context": "First-line HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma", "reads": "Mature overall survival extends early response and interim progression", "boundary": "Confined to the randomized first-line regimen; exploratory CPS subsets and single-trial maturation do not establish cure or independent validation." }, { "units": [ "U-OlympiAD" ], "context": "Germline BRCA-mutated, HER2-negative metastatic breast cancer", "reads": "Progression-free survival benefit does not establish overall survival gain across prespecified or post-hoc follow-up", "boundary": "Metastatic setting distinct from adjuvant OlympiA; post-hoc follow-up and exploratory first-line subgroup analysis do not demonstrate overall population survival benefit, equivalence, or independent replication." } ], "changesMind": "A new prespecified analysis can revise the conclusion for its own endpoint and population. A subgroup association or post hoc explanation will be labeled separately rather than used to overwrite an unsuccessful primary test.", "next": [ "Track which report supplies each endpoint and its follow-up date.", "Revisit related question pairs when survival or safety matures.", "Keep treatment-phase and comparator differences in every cross-study table.", "Distinguish exploratory biomarker subgroups from full randomized populations and corroborate regulatory summaries when correspondence lacks an abstract.", "Distinguish planned prespecified survival testing from post-hoc extended follow-up, and isolate exploratory prior-therapy subgroup hypotheses from intention-to-treat conclusions." ], "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8; reviewed by Muse Spark1.3; source-checked and integrated by Codex (GPT-6)" }, { "id": "RB-03", "program": "gxb", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6), original synthesis; additions by Gemini Flash3.8, reviewed by Muse Spark1.3, integrated by Codex (GPT-6)", "title": "From residual-disease detection to a useful intervention", "summary": "A blood signal can be associated with recurrence without proving that acting on it improves patient outcomes. The useful comparison is a defined testing-and-treatment strategy against an appropriate alternative.", "scope": "Narrative synthesis of selected gastric, breast and colorectal records on residual disease, recurrence and response. It does not cover every assay or disease setting.", "units": [ "U-ctDNAYang20", "U-ctDNAYuan23", "U-cTRAKTN", "U-DYNAMIC", "U-NICHE2", "U-DOSTrectal", "U-KATHERINE", "U-DYNAMIC3", "U-CIRCULATE-AIO" ], "pairs": [ "QP-21", "QP-22", "QP-23", "QP-24" ], "sections": [ { "heading": "Begin with the claim the study can actually test", "paragraphs": [ "The gastric postoperative ctDNA cohorts link detection with later recurrence outcomes. They are informative about prognosis in the observed patients. They do not randomize a rule for changing treatment because of a blood result. A prognostic association therefore cannot establish the benefit of escalation or de-escalation based on that assay.", "Timing is part of the claim. A result assessed after surgery, after adjuvant treatment, or at any point during follow-up does not describe the same decision. Pooling these into a single ctDNA-positive category can erase when the information was available and what action could have followed it." ], "units": [ "U-ctDNAYang20", "U-ctDNAYuan23" ] }, { "heading": "Earlier detection is not automatically an intervention window", "paragraphs": [ "c-TRAK TN followed a surveillance population and attempted intervention after molecular detection. Many patients allocated to intervention already had metastases on staging, and only a small subgroup began the study treatment. Those transitions matter: entering surveillance, having a detected signal, being eligible for intervention and receiving treatment are different denominators.", "The amended allocation and small treated subgroup do not establish a general comparative survival effect. They also do not prove that every possible ctDNA-guided approach is ineffective. The study exposes a practical research question: can a test identify an actionable state early enough for an intervention with demonstrated benefit?" ], "units": [ "U-cTRAKTN" ] }, { "heading": "A randomized strategy answers a more specific question", "paragraphs": [ "DYNAMIC tested ctDNA-guided management against standard management in its stage II colon cancer population. Its reduced chemotherapy use and recurrence-free survival findings belong to that complete strategy. The randomization was not a separate test of chemotherapy versus observation within every ctDNA-positive subgroup.", "Meeting a noninferiority criterion does not show that the two strategies have identical risk, and a negative ctDNA result does not prove eradication. Long-term follow-up extends the same trial. Transfer to gastric cancer, breast cancer, another colorectal stage or a different assay requires evidence that addresses the new setting." ], "units": [ "U-DYNAMIC" ] }, { "heading": "De-escalation and escalation face distinct tests in locally advanced disease", "paragraphs": [ "DYNAMIC-III tested a ctDNA-guided management strategy in stage III colon cancer, combining de-escalation for ctDNA-negative patients with escalation for ctDNA-positive patients against standard care. In the ctDNA-negative cohort, de-escalation reduced oxaliplatin use and hospitalizations but failed to meet the prespecified noninferiority margin for recurrence-free survival. Failing a noninferiority margin indicates that noninferiority was not established; it does not demonstrate identical outcomes, nor does that failure alone establish inferiority. Among ctDNA-positive patients, treatment escalation showed no demonstrated improvement in recurrence-free survival over standard management.", "The stage II DYNAMIC result does not establish the same strategy in stage III disease. The unmet de-escalation criterion and absence of demonstrated escalation benefit in DYNAMIC-III remain separate findings; neither establishes that every ctDNA-guided strategy is ineffective." ], "units": [ "U-DYNAMIC3" ] }, { "heading": "Randomizing test-positive patients tests treatment efficacy rather than overall strategy", "paragraphs": [ "The CIRCULATE (AIO/ABCSG) trial investigated adjuvant chemotherapy versus observation within patients with ctDNA-positive, mismatch-repair-proficient/microsatellite-stable stage II colon cancer. This approach differs from the whole-strategy design of DYNAMIC in stage II disease, which randomized the broader population to a testing-and-treatment strategy rather than isolating treatment efficacy within positive patients. However, premature trial closure due to funding expiry limited recruitment, and the primary intention-to-treat analysis did not meet its disease-free survival endpoint.", "Although a per-protocol analysis suggested an advantage for patients who received chemotherapy, that selected subset excluded assigned patients who never initiated treatment and cannot rescue or replace the unmet primary intention-to-treat result. As with negative strategy evaluations, failure to demonstrate benefit in this prematurely closed trial does not establish an absence of benefit, nor can these stage II results be generalized across all ctDNA strategies, disease stages, or cancer types." ], "units": [ "U-CIRCULATE-AIO" ] }, { "heading": "Residual tissue, blood and complete response are different observations", "paragraphs": [ "KATHERINE selected residual invasive disease after neoadjuvant treatment and then compared postoperative therapies. It is evidence about a tissue-defined treatment setting. It does not validate a ctDNA decision rule merely because both questions concern residual disease.", "NICHE-2 assessed pathological response in resected colon tumours; the dostarlimab rectal study assessed clinical complete response and organ preservation in a different setting. Their response definitions and subsequent management differ. Neither a pathological complete response nor a clinical complete response can be renamed permanent eradication on the basis of the response count alone." ], "units": [ "U-KATHERINE", "U-NICHE2", "U-DOSTrectal" ] }, { "heading": "The next evidence needs to connect the whole pathway", "paragraphs": [ "A useful study must make its population, assay, sampling time, result threshold, intervention rule and comparator explicit. It must then evaluate outcomes that matter for that question, including harms and follow-up long enough to interpret recurrence. Improving detection alone does not complete this chain.", "The library therefore keeps prognostic association, feasibility of intervention, randomized strategy benefit and long-term disease control as separate claims. This preserves a place for informative negative or incomplete studies without promoting an untested management rule." ], "units": [ "U-ctDNAYuan23", "U-cTRAKTN", "U-DYNAMIC" ] } ], "comparison": [ { "units": [ "U-ctDNAYang20", "U-ctDNAYuan23" ], "context": "Gastric cancer after surgery or adjuvant treatment", "reads": "Observed association between ctDNA detection and recurrence", "boundary": "No randomized evidence here that acting on the result improves outcomes." }, { "units": [ "U-cTRAKTN" ], "context": "ctDNA surveillance and attempted intervention in selected TNBC", "reads": "Detection-to-staging-to-treatment feasibility", "boundary": "Changing allocation and a small treated group limit comparative conclusions." }, { "units": [ "U-DYNAMIC" ], "context": "Stage II colon cancer management strategy", "reads": "Randomized comparison of testing-guided and standard management", "boundary": "Do not infer a positive-subgroup chemotherapy effect or transfer to another cancer." }, { "units": [ "U-NICHE2", "U-DOSTrectal" ], "context": "Selected dMMR colon or rectal cancer", "reads": "Study-defined pathological or clinical response", "boundary": "Different response definitions and follow-up; response alone does not establish cure." }, { "units": [ "U-DYNAMIC3" ], "context": "Stage III colon cancer de-escalation and escalation strategy", "reads": "Randomized comparison of ctDNA-guided de-escalation/escalation and standard management", "boundary": "Noninferiority margin not met for de-escalation and no demonstrated benefit from escalation; do not generalize across stages or strategies." }, { "units": [ "U-CIRCULATE-AIO" ], "context": "Selected ctDNA-positive, pMMR/MSS stage II colon cancer", "reads": "Randomized comparison of chemotherapy versus observation in ctDNA-positive patients", "boundary": "Underaccrual and unmet primary ITT DFS; selected per-protocol finding cannot rescue primary, and failure to demonstrate benefit is not proof of absence." } ], "changesMind": "A prospective comparative study linking a prespecified assay and intervention rule to recurrence, survival and harms in the receiving population could change the held judgment. Better detection performance alone would not.", "next": [ "Separate landmark sampling from detection at any time during follow-up.", "Keep surveillance, test-positive, eligible and treated denominators explicit.", "Look for comparative strategy results in the target cancer before transferring an MRD conclusion.", "Distinguish whole-strategy randomizations from treatment trials restricted to biomarker-positive cohorts, and do not use selected per-protocol analyses to rescue an unmet primary endpoint." ], "updated": "2026-09-30", "updatedBy": "Gemini Flash3.8; reviewed by Muse Spark1.3; integrated by Codex (GPT-6)" }, { "id": "RB-04", "program": "breast", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6)", "title": "ESR1: from tissue detection to a treatment-strategy question", "summary": "Cross-sectional samples, paired specimens and an external cohort address different uncertainties. Their findings provide context for randomized switching trials without replacing those trials.", "scope": "Focused narrative synthesis of existing ESR1 records. Includes an inconclusive external evaluation; not a systematic review, causal analysis or treatment recommendation.", "units": [ "U-A2", "U-A5", "U-Razavi18", "U-PADA1", "U-SERENA6" ], "pairs": [ "QP-05", "QP-08" ], "sections": [ { "heading": "Start with the unit of comparison", "paragraphs": [ "A2 compared primary and metastatic specimens from different sampled groups in the MSK breast dataset. That contrast describes a prevalence difference in the observed material. Sampling, treatment histories and patient selection can contribute to it; the contrast does not follow a mutation appearing within each individual.", "A5 instead selected one primary and one metastatic specimen for each eligible patient from the same MSK collection. More discordant pairs had a reported ESR1 variant only in the metastatic specimen. This supports a paired detection pattern under the specified rules, while reusing the same collection rather than providing another independent cohort." ], "units": [ "U-A2", "U-A5", "U-Razavi18" ] }, { "heading": "A pair is not a recorded evolutionary sequence", "paragraphs": [ "Some selected metastatic specimens were collected at the same recorded time as the primary specimen, or earlier. Variant non-detection also depends on assay coverage and sensitivity. The paired comparison therefore does not establish when a mutation arose, which treatment selected it, or whether the alteration caused progression.", "The A5 record retains its original plan and an explicit decoder amendment for missing Entrez annotations. The implementation change followed input acquisition, and aggregate results were disclosed before the amended execution. It is a documented retrospective analysis, not a claim of prospectively blinded code development." ], "units": [ "U-A5" ] }, { "heading": "Keep the inconclusive external result visible", "paragraphs": [ "CV-A2 evaluated the A2 direction using the separately collected MBCproject material. The comparison used breast tissue sampled before documented metastatic disease and distant metastatic tissue, with one selected specimen per patient. These metadata-based categories are imperfect proxies and come from a project recruiting people with metastatic disease.", "The point estimate favored greater ESR1 detection in distant metastases, but the confidence interval crossed no difference and the prespecified evaluation remained inconclusive. This is neither confirmation nor proof that the groups are equivalent. Study-level recruitment differs from MSK, but globally anonymized donor overlap cannot be completely excluded." ], "units": [ "U-A2" ] }, { "heading": "A clinical switching strategy requires its own comparison", "paragraphs": [ "PADA-1 and SERENA-6 randomized strategies after an ESR1 alteration was detected in blood before radiographic progression. Their reported progression-free survival benefits belong to the actual eligibility, assay, treatment and comparator in each trial. Detecting a tissue prevalence difference is not the intervention those trials tested.", "A shared selection time followed by randomization should not be dismissed as a lead-time artifact merely because treatment changed before progression. At the same time, progression-free survival does not stand in for demonstrated overall survival, later-line outcomes or every safety endpoint. Each additional claim needs its own result and follow-up." ], "units": [ "U-PADA1", "U-SERENA6" ] }, { "heading": "The next useful test", "paragraphs": [ "A larger independently collected cohort with compatible specimen definitions, patient-level selection and verified gene coverage could reduce uncertainty around the observational question. Eligibility and analysis rules should be fixed before inspecting the molecular outcome. Repeated releases of overlapping patients should not be counted as independent confirmations.", "For the clinical question, update the original switching trials as longer follow-up and harm data become available. An observational association, a paired internal analysis, an inconclusive external evaluation and a randomized treatment comparison can coexist without being reduced to one success label." ], "units": [ "U-A2", "U-A5", "U-PADA1", "U-SERENA6" ] } ], "comparison": [ { "units": [ "U-A2" ], "context": "Different primary and metastatic sampled groups", "reads": "Observed ESR1 prevalence contrast; CV-A2 adds an inconclusive external evaluation", "boundary": "Patient selection, metadata proxies and measurement differences remain." }, { "units": [ "U-A5" ], "context": "Selected primary/metastatic specimens from the same MSK patients", "reads": "Paired detection pattern with an explicit implementation-amendment history", "boundary": "Same collection as A2; neither acquisition timing nor treatment causation established." }, { "units": [ "U-PADA1", "U-SERENA6" ], "context": "Blood-guided switching before radiographic progression", "reads": "Randomized strategy comparisons with reported progression-free survival benefit", "boundary": "Retain each trial population, treatment, harms and endpoint maturity." } ], "changesMind": "Compatible external patient data with narrower uncertainty would revise the observational judgment. Mature randomized survival and harm results would revise the clinical-strategy judgment; one cannot substitute for the other.", "next": [ "Assess a larger separate cohort before viewing molecular outcomes.", "Retain the inconclusive CV-A2 result when adding future evaluations.", "Link mature follow-up to the original switching-trial unit." ] }, { "id": "RB-05", "program": "breast", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6) with Gemini 3.8 Flash", "title": "Endocrine therapy after surgery: suppression and longer treatment ask different questions", "summary": "Four trials examine when to intensify or extend endocrine therapy. Their findings depend on ovarian function, previous treatment, endpoint definition and follow-up; a single recurrence-prevention label loses those distinctions.", "scope": "Selected narrative synthesis of library records, not a systematic review or treatment guideline.", "units": [ "U-SOFT", "U-ASTRRA", "U-ATLAS", "U-NSABPB42" ], "pairs": [ "QP-14" ], "sections": [ { "heading": "Start with the treatment decision", "paragraphs": [ "Ovarian suppression trials ask whether adding suppression during initial adjuvant endocrine treatment improves outcomes in selected premenopausal patients. Extension trials ask whether treatment should continue after an earlier course. These are different comparisons, not successive steps validated by one evidence chain. Hormone receptor positivity also does not imply that every participant had HER2-negative disease. The question is not simply whether more endocrine treatment is better. It is which added treatment, after which exposure, changes which outcome in a defined population. Separating these decisions also makes late benefits and adverse effects easier to evaluate." ], "units": [ "U-SOFT", "U-ASTRRA", "U-ATLAS", "U-NSABPB42" ] }, { "heading": "SOFT: preserve three arms and separate endpoints", "paragraphs": [ "SOFT compared tamoxifen alone, tamoxifen plus ovarian suppression, and exemestane plus suppression. The primary comparison of adding suppression to tamoxifen did not significantly improve five-year disease-free survival (DFS). Final follow-up favored tamoxifen plus suppression for breast cancer-free interval, a different endpoint that does not rewrite that initial test. Reported survival differences in selected high-risk HER2-negative subgroups cannot be generalized to everyone enrolled. This brief uses SOFT-specific findings; the pooled SOFT/TEXT comparison is neither another independent SOFT trial nor a TEXT-only result. SOFT included women with and without prior chemotherapy; that eligibility distinction matters when comparing suppression trials." ], "units": [ "U-SOFT" ] }, { "heading": "ASTRRA: ovarian function defines the population", "paragraphs": [ "ASTRRA studied ER-positive disease after chemotherapy in women who remained premenopausal or recovered ovarian function. Adding two years of suppression to five years of tamoxifen improved DFS, including at eight-year follow-up. The later overall-survival comparison was not statistically significant; the earlier survival finding cannot replace it. The later comparison leaves survival benefit uncertain while supporting the DFS finding. Quantitative toxicity was not supplied in the saved abstracts. ASTRRA did not directly compare two with five years of suppression." ], "units": [ "U-ASTRRA" ] }, { "heading": "ATLAS: read benefit alongside its safety population", "paragraphs": [ "ATLAS compared continuing tamoxifen to ten years with stopping at five. Lower recurrence and breast-cancer mortality concern the ER-positive population; higher pulmonary-embolus and endometrial-cancer incidence were assessed across receptor groups. These findings fall outside the stated correction scope. This brief omits affected cardiac and mortality categories and appendix subgroup estimates; the separate center-exclusion letter was not reviewed in full. ATLAS supplies evidence for tamoxifen extension, not a direct comparison with an aromatase inhibitor. Long-term disease control should be considered alongside these serious harms rather than converted into universal net benefit." ], "units": [ "U-ATLAS" ] }, { "heading": "B-42: longer follow-up does not erase the original boundary", "paragraphs": [ "NSABP B-42 compared five additional years of letrozole with placebo in postmenopausal stage I–IIIA hormone-receptor-positive patients who were disease-free after approximately five years of an aromatase inhibitor, or tamoxifen followed by one. Initial DFS missed its adjusted significance threshold (P=.048 versus .0418). The ten-year update, not prespecified in the protocol, reported improved DFS and fewer distant recurrences without a significant overall-survival improvement. DFS included second primary malignancy and death, not recurrence alone. Fracture and arterial-event comparisons did not establish absence of harm." ], "units": [ "U-NSABPB42" ] } ], "comparison": [ { "units": [ "U-SOFT", "U-ASTRRA" ], "context": "Premenopausal treatment intensification", "reads": "Ovarian suppression added to defined endocrine regimens", "boundary": "Ovarian function, chemotherapy history and endpoint matter." }, { "units": [ "U-ATLAS", "U-NSABPB42" ], "context": "Treatment extension", "reads": "Continuing tamoxifen or adding letrozole after prior therapy", "boundary": "Different preceding treatments and populations prevent direct ranking." } ], "changesMind": "Direct comparisons with matched eligibility, prespecified endpoints and mature benefit–harm assessment would refine these judgments. Follow-up updates the original trial rather than adding independent replication.", "next": [ "Track late efficacy and harms together.", "Keep prior treatment and endpoint definitions attached to every comparison." ] }, { "id": "RB-06", "program": "breast", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Codex (GPT-6) with Gemini 3.8 Flash", "title": "HER2-positive breast cancer de-escalation: distinguishing components and design limits", "summary": "Four trials evaluate de-escalation of distinct treatment components in HER2-positive early breast cancer: chemotherapy intensity, anthracycline inclusion or trastuzumab duration. Single-arm cohorts cannot establish equivalence; a superiority trial without a significant result does not prove equivalence; and descriptive long-term percentages or exploratory subgroups cannot rescue a failed non-inferiority result.", "scope": "Selected narrative synthesis of library records, not a systematic review or treatment guideline.", "units": [ "U-APT", "U-PERSEPHONE", "U-TRAIN2", "U-ShortHER" ], "pairs": [ "QP-37" ], "sections": [ { "heading": "Distinguish modified components from study designs", "paragraphs": [ "De-escalation strategies in HER2-positive early breast cancer address fundamentally distinct questions. Shortening trastuzumab duration differs from reducing chemotherapy intensity or omitting anthracyclines. Permissible inferences depend on protocol design: uncontrolled cohorts provide descriptive outcomes, whereas randomized trials test specific non-inferiority or superiority hypotheses. Conflating these designs obscures critical uncertainties." ], "units": [ "U-APT", "U-PERSEPHONE", "U-TRAIN2", "U-ShortHER" ] }, { "heading": "APT: single-arm evaluation in selected small tumors", "paragraphs": [ "The APT trial evaluated chemotherapy de-escalation, giving weekly paclitaxel for 12 weeks with trastuzumab, then trastuzumab monotherapy completing one year. It enrolled selected patients with tumors up to 3 cm, predominantly node-negative, though amendments permitted limited micrometastases. Favorable 10-year invasive disease-free survival cannot establish equivalence or non-inferiority without a control arm, and invasive disease-free survival includes contralateral cancers and deaths." ], "units": [ "U-APT" ] }, { "heading": "PERSEPHONE: non-inferiority met for six months of trastuzumab", "paragraphs": [ "PERSEPHONE randomized patients to 6 versus 12 months of adjuvant trastuzumab with chemotherapy and met its prespecified non-inferiority criterion based on a 3 percentage-point absolute four-year DFS margin (HR 1.10, 90% CI 0.96–1.26). In the trastuzumab-received safety population, 6 months reduced early stopping due to cardiotoxicity (61/1977 [3%] vs 146/1941 [8%], p<0.0001). However, meeting this margin is not identical efficacy or universal interchangeability, nor does it validate shorter courses or dual blockade." ], "units": [ "U-PERSEPHONE" ] }, { "heading": "ShortHER: nine-week strategy failed original non-inferiority", "paragraphs": [ "ShortHER randomized 9 weeks versus 1 year of adjuvant trastuzumab with different chemotherapy schedules in resected HER2-positive patients who were node-positive or node-negative with specified risk factors. The upper limit of the primary disease-free survival hazard ratio confidence interval exceeded the prespecified 1.29 margin, so non-inferiority was not established. At median 9 years, similar 10-year survival percentages do not reverse that conclusion. Exploratory outcomes with four or more positive nodes were poorer in the short-duration arm; subgroup patterns cannot establish which individuals can safely receive a shorter course. Differing chemotherapy backbones prevent isolating duration from the chemotherapy-strategy difference." ], "units": [ "U-ShortHER" ] }, { "heading": "TRAIN-2: anthracycline omission with dual blockade lacks equivalence proof", "paragraphs": [ "TRAIN-2 compared neoadjuvant chemotherapy with or without anthracyclines, both given with concurrent trastuzumab and pertuzumab in stage II–III disease. There was no statistically significant difference in pathological complete response in evaluable patients or in the secondary three-year event-free survival analysis. However, this nonsignificant superiority trial provides no equivalence proof. In the treatment-received safety population, omitting anthracyclines reduced grade 3 or worse febrile neutropenia. Pathological complete response is not cure, and concurrent dual blockade prevents isolating either antibody's contribution." ], "units": [ "U-TRAIN2" ] } ], "comparison": [ { "units": [ "U-PERSEPHONE", "U-ShortHER" ], "context": "Adjuvant trastuzumab duration reduction", "reads": "PERSEPHONE met its prespecified margin for six months; ShortHER did not establish non-inferiority for nine weeks.", "boundary": "Different regimens, populations and margins prevent a cross-trial ranking of treatment duration." }, { "units": [ "U-APT", "U-TRAIN2" ], "context": "Chemotherapy backbone and agent reduction", "reads": "Single-agent paclitaxel in small low-stage tumors or anthracycline omission with dual HER2 blockade.", "boundary": "Single-arm cohorts cannot establish equivalence, and nonsignificant superiority trials provide no equivalence proof." }, { "units": [ "U-APT", "U-PERSEPHONE", "U-TRAIN2", "U-ShortHER" ], "context": "Evaluative limits of study designs", "reads": "Interpreting clinical results strictly according to protocol-defined statistical hypotheses.", "boundary": "Prespecified non-inferiority success within defined margins must not be conflated with single-arm trials, failed non-inferiority, or trials lacking equivalence proof." } ], "changesMind": "Direct randomized comparisons with matched chemotherapy backbones, prespecified non-inferiority margins, and mature safety assessments would refine these boundaries. Extended follow-up updates existing trials rather than providing independent replication.", "next": [ "Specify the exact treatment component modified alongside protocol-defined statistical hypotheses and non-inferiority margins.", "Distinguish intention-to-treat efficacy populations from treatment-received safety cohorts when reporting toxicities." ] }, { "id": "RB-07", "program": "breast", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Muse Spark1.3", "title": "Genomic risk versus chemotherapy benefit in early HR-positive/HER2-negative breast cancer", "summary": "TAILORx, RxPONDER and MINDACT test different assays in populations defined by different nodal status, score ranges and menopausal status. A favorable prognosis without chemotherapy, meeting a chemotherapy-omission benchmark, validation of a prognostic model and exploratory patterns by age or ovarian reserve are not randomized proof of equal treatment outcomes, nor do they amount to a validated policy of biomarker-guided chemotherapy omission.", "scope": "Selected narrative synthesis of library records and official abstracts; not a systematic review or treatment guideline.", "units": [ "U-TAILORx", "U-RxPONDER", "U-MINDACT" ], "pairs": [ "QP-40" ], "sections": [ { "heading": "Different tests, populations and questions", "paragraphs": [ "TAILORx and RxPONDER use the 21-gene recurrence score on a 0-100 scale; MINDACT uses the 70-gene signature with clinical risk from clinicopathological features. TAILORx randomized recurrence scores 11-25 in node-negative disease, RxPONDER randomized scores 25 or lower with one to three positive nodes, and MINDACT randomized chemotherapy only when clinical and genomic classifications disagreed in operable disease with up to three positive nodes. Endpoints also differ: invasive disease-free survival includes second cancers and death, while distant metastasis-free or distant relapse-free survival is narrower. The overall MINDACT eligibility population was not restricted to hormone receptor-positive, HER2-negative disease; its age analysis concerned that subgroup." ], "units": [ "U-TAILORx", "U-RxPONDER", "U-MINDACT" ] }, { "heading": "TAILORx: noninferiority in node-negative scores 11-25", "paragraphs": [ "Among 10273 enrolled women, 9719 were eligible with follow-up and 6711 with scores 11-25 entered the randomized comparison of endocrine therapy alone versus chemoendocrine therapy. Endocrine therapy alone was noninferior for invasive disease-free survival (HR endocrine versus chemoendocrine 1.08, 95% CI 0.94-1.24). At 9 years, invasive disease-free survival was 83.3% versus 84.3%, freedom from distant recurrence 94.5% versus 95.0%, and overall survival 93.9% versus 93.8%. Chemotherapy benefit varied with combined score and age (P=0.004), with some benefit in women 50 years or younger with scores 16-25. Lower- and higher-score groups did not receive the same randomized comparison.", "Clinical risk by tumor size and grade added prognostic information to the score, and a later RSClin model combining score, grade, size and age improved prognostic estimates in 10004 women across three trials with validation in 1098 registry women. That late-recurrence prognostic validation is not a new randomized treatment comparison and does not prove benefit of a particular extended regimen." ], "units": [ "U-TAILORx" ] }, { "heading": "RxPONDER: menopause-dependent effect in node-positive scores 25 or lower", "paragraphs": [ "RxPONDER randomized 5083 women with one to three positive nodes and recurrence score 25 or lower; 5018 participated. Chemotherapy effect on invasive disease-free survival differed by menopausal status (interaction P=0.008). In postmenopausal women, 5-year invasive disease-free survival was 91.9% endocrine-only versus 91.3% chemoendocrine (HR for chemoendocrine versus endocrine-only therapy 1.02, 95% CI 0.82-1.26), without demonstrated benefit. In premenopausal women it was 89.0% versus 93.9% (HR for chemoendocrine versus endocrine-only therapy 0.60, 95% CI 0.43-0.83); distant relapse-free survival also favored chemoendocrine therapy (HR 0.58, 95% CI 0.39-0.87). Relative benefit did not increase with higher score within the tested range.", "A later ovarian-reserve analysis in 1556 participants aged below 55 years used predefined cut points in available pretreatment serum. AMH at or above 10 pg/ml, present in 64%, showed superior invasive disease-free survival with chemoendocrine therapy (HR 0.46, 95% CI 0.33-0.65), while AMH below 10 pg/ml, present in 36%, did not (HR 1.27, 95% CI 0.81-1.99; treatment-marker interaction adjusted P=0.0034). Because chemotherapy was not randomized against optimized ovarian suppression, neither the main younger-women result nor this subset isolates a cytotoxic from an ovarian mechanism, and the subset does not independently validate a biomarker-guided treatment policy." ], "units": [ "U-RxPONDER" ] }, { "heading": "MINDACT: omission benchmark is not a randomized equivalence result", "paragraphs": [ "MINDACT enrolled 6693 patients. Its original primary test asked whether high-clinical-risk/low-genomic-risk patients receiving no chemotherapy exceeded a prespecified 92% lower-bound for 5-year distant metastasis-free survival. At updated follow-up the adherent no-chemotherapy primary population of 644 patients reached 95.1% (95% CI 93.1-96.6). Meeting that benchmark describes outcome without chemotherapy; it does not establish identical outcomes between treatments.", "The separate intention-to-treat randomized comparison allocated 749 to chemotherapy and 748 to no chemotherapy. Eight-year distant metastasis-free survival was 92.0% (95% CI 89.6-93.8) versus 89.4% (86.8-91.5) (HR 0.66, 95% CI 0.48-0.92). Exploratory hormone receptor-positive/HER2-negative age analysis showed an absolute difference of 5.0 percentage points (95% CI -0.5 to 10.4) at or below 50 years and 0.2 percentage points (-4.0 to 4.4) above 50 years, with wide uncertainty. A selected above-50 high-risk-feature analysis reported 8-year distant metastasis-free survival without chemotherapy of 87.9% for tumors larger than 2 cm, 91.3% for grade 3 and 89.6% for node-positive disease, with chemotherapy versus no-chemotherapy differences of 1.2%, -2.2% and 0.7%. These underpowered exploratory results do not validate age alone as an omission rule. All reports are follow-ups of one trial, not new trials." ], "units": [ "U-MINDACT" ] } ], "comparison": [ { "units": [ "U-TAILORx", "U-RxPONDER" ], "context": "21-gene score in node-negative versus node-positive disease", "reads": "TAILORx shows noninferiority of endocrine therapy alone for scores 11-25 without nodes; RxPONDER shows menopause-dependent chemotherapy effects for scores 25 or lower with one to three nodes.", "boundary": "Different nodal status, score ranges and subgroup variables prevent one shared omission rule." }, { "units": [ "U-MINDACT" ], "context": "Original omission benchmark versus later randomized comparison", "reads": "The 644-patient no-chemotherapy benchmark exceeded 92%, while the separate 749-versus-748 randomized comparison favored chemotherapy at 8 years.", "boundary": "A met single-arm-style benchmark must not be read as proof of equal randomized outcomes." }, { "units": [ "U-TAILORx", "U-RxPONDER", "U-MINDACT" ], "context": "Prognostic information versus treatment-policy evidence", "reads": "Clinical risk, RSClin validation and AMH-subset interactions refine prognosis or generate hypotheses; only prespecified randomized comparisons test treatment benefit.", "boundary": "Prognostic validation and exploratory subsets do not establish biomarker-guided treatment selection or an ovarian mechanism." } ], "changesMind": "Prespecified marker-treatment interaction plus independent validation of a marker-guided strategy in the same nodal, menopausal and score setting, or direct comparison separating ovarian suppression from cytotoxic contribution, would update the applicable boundaries.", "next": [ "Record enrolled, randomized and primary-test populations separately with score, nodal and menopausal definitions.", "Track prognosis, marker-treatment interaction and marker-guided strategy usefulness as separate evidence items." ] }, { "id": "RB-08", "program": "colorectal", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Gemini Flash 3.8", "title": "What three bevacizumab trials actually compare", "summary": "This brief synthesizes three randomized trials evaluating bevacizumab-containing regimens: AVAGAST, SUNLIGHT, and TRIBE2. The observed outcomes diverge across trials that differ in tumor type, chemotherapy backbone, disease setting and endpoint structure. However, cross-trial differences do not demonstrate why outcomes differ, nor do they establish causal effect modification. In advanced gastric cancer, adding first-line bevacizumab to chemotherapy did not produce a statistically significant improvement in overall survival. In refractory metastatic colorectal cancer, bevacizumab added to trifluridine-tipiracil improved overall and progression-free survival. In previously untreated metastatic colorectal cancer, TRIBE2 evaluated a chemotherapy strategy spanning multiple treatment lines, with bevacizumab given in both study arms, so it provides no estimate of the independent effect of adding bevacizumab. Cross-trial comparisons cannot be used for drug ranking or treatment selection.", "scope": "Evidence is strictly restricted to supplied records U-AVAGAST, U-SUNLIGHT, and U-TRIBE2 under a comparative trial methodology framework. This brief is not a systematic review, meta-analysis, or clinical treatment guideline.", "units": [ "U-AVAGAST", "U-SUNLIGHT", "U-TRIBE2" ], "pairs": [], "sections": [ { "heading": "Distinct Clinical Settings and Primary Endpoint Divergence", "paragraphs": [ "AVAGAST evaluated the addition of bevacizumab to first-line fluoropyrimidine-cisplatin chemotherapy in advanced gastric or gastro-oesophageal junction adenocarcinoma. AVAGAST did not meet its primary overall survival endpoint. Secondary progression-free survival and objective response rate favored bevacizumab, but secondary gains cannot reverse primary overall survival failure, and exploratory regional subgroup differences do not establish efficacy. In refractory metastatic colorectal cancer, SUNLIGHT evaluated bevacizumab plus trifluridine-tipiracil versus trifluridine-tipiracil monotherapy after prior standard therapies. SUNLIGHT met its primary endpoint, showing prolonged overall survival and improved progression-free survival. Because these trials evaluated distinct tumor biologies, therapy lines, and companion backbones, their diverging results reflect distinct trial contexts rather than explaining why outcomes differ, precluding cross-trial ranking." ], "units": [ "U-AVAGAST", "U-SUNLIGHT" ] }, { "heading": "Chemotherapy Continuum Strategy Versus Drug Addition in TRIBE2", "paragraphs": [ "In previously untreated metastatic colorectal cancer, TRIBE2 evaluated a multi-line continuum-care strategy rather than isolating bevacizumab efficacy. The trial compared upfront triplet chemotherapy (FOLFOXIRI) plus bevacizumab with reintroduction after disease progression against sequential doublets (mFOLFOX6 followed by FOLFIRI), also given with bevacizumab. Crucially, because bevacizumab was administered in both arms, TRIBE2 provides no comparative estimate or inference regarding the independent effect of adding bevacizumab. Instead, it tests upfront chemotherapy intensification against sequential administration within a planned sequence. The primary endpoint was progression-free survival 2, measuring time from randomization to disease progression on post-first-progression therapy or death. This strategy endpoint evaluates disease control across successive treatment lines rather than conventional single-line progression-free survival or overall survival, and the record does not incorporate updated overall survival." ], "units": [ "U-TRIBE2" ] }, { "heading": "Functional Trajectories, Quality of Life, and Toxicity Burdens", "paragraphs": [ "In the SUNLIGHT quality-of-life analysis, scores in both arms remained stable without clinically meaningful change; the combination delayed definitive deterioration and performance-status worsening. These reported outcomes must be distinguished from separate analyses of maintained-performance cohorts, which select a surviving patient subset. Comprehensive trial evaluation also requires assessing harms. In TRIBE2, upfront triplet intensification increased serious adverse events, severe diarrhea, neutropenia, and first-line treatment-related deaths compared with sequential doublet therapy, while reported severe hypertension was numerically lower in the triplet arm. In SUNLIGHT, common toxicities included neutropenia, nausea, and anemia, with no treatment-related deaths. In AVAGAST, reported severe adverse events included neutropenia, anemia, and decreased appetite without novel safety signals." ], "units": [ "U-AVAGAST", "U-SUNLIGHT", "U-TRIBE2" ] } ], "comparison": [ { "context": "First-line advanced gastric or gastro-oesophageal junction adenocarcinoma, evaluating bevacizumab plus fluoropyrimidine-cisplatin versus placebo plus fluoropyrimidine-cisplatin.", "reads": "Tests the addition of bevacizumab to first-line chemotherapy; demonstrated improved secondary progression-free survival and objective response rate, but failed to achieve a statistically significant improvement in the primary overall survival endpoint.", "boundary": "Cannot establish an overall survival benefit for bevacizumab in advanced gastric cancer; secondary progression-free survival gains, response rate improvements, and exploratory regional subgroup differences cannot reverse primary overall survival failure.", "units": [ "U-AVAGAST" ] }, { "context": "Refractory metastatic colorectal cancer after at most two prior chemotherapy regimens in patients with ECOG performance status 0-1, evaluating trifluridine-tipiracil plus bevacizumab versus trifluridine-tipiracil monotherapy.", "reads": "Tests the addition of bevacizumab to trifluridine-tipiracil; demonstrated significantly improved overall survival and progression-free survival as reported in this record, along with delayed time to ECOG performance-status worsening to >=2.", "boundary": "Cannot establish efficacy in earlier lines of therapy or in patients with poorer performance status; exploratory KRAS subgroup analyses do not establish predictive interactions, maintained-performance analyses select a subgroup, and findings cannot explain cross-trial divergences.", "units": [ "U-SUNLIGHT" ] }, { "context": "Previously untreated unresectable metastatic colorectal cancer, evaluating upfront triplet chemotherapy (FOLFOXIRI) plus bevacizumab with post-progression reintroduction versus sequential doublets (mFOLFOX6 followed by FOLFIRI) plus bevacizumab.", "reads": "Tests upfront multi-line chemotherapy intensification and reintroduction against sequential doublet administration within a multi-line continuum strategy; demonstrated a statistically significant improvement in the primary strategy endpoint of progression-free survival 2 (PFS2).", "boundary": "Cannot isolate the independent effect of adding bevacizumab because bevacizumab was administered in both study arms; primary endpoint was strategy-specific PFS2, not single-line/first-line PFS; this record does not summarize an updated overall survival analysis.", "units": [ "U-TRIBE2" ] } ], "changesMind": "Source-grounded future evidence needed to revise this synthesis includes any updated overall survival analysis for TRIBE2 beyond this record, if available, or full-text appraisal of currently unread published correspondence across the trials as identified in the supplied records.", "next": [ "Retrieve and analyze the full text of published correspondence and commentaries currently unread for AVAGAST, SUNLIGHT, and TRIBE2.", "Check clinical trial registry records and literature cited in the supplied records for any updated overall survival analysis for TRIBE2 beyond this record, if available.", "Examine the progression-free survival 2 (PFS2) endpoint definition as stated in the TRIBE2 record.", "Assess post-progression therapy exposure and subsequent treatment distribution as reported in the AVAGAST and SUNLIGHT trial records, if reported." ] }, { "id": "RB-09", "program": "gxb", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Muse Spark1.3; Gemini Flash3.8 review; Codex source reconciliation", "reviewedBy": "gemini-3.8-flash-high", "title": "ERBB2 co-amplification: one descriptive analysis, two different cohort results", "summary": "The original TCGA comparison described higher distant-locus co-amplification in selected ERBB2-amplified gastric tumors. Two later cohort evaluations, performed internally and using the same breast comparator, produced one supported comparison and one inconclusive comparison. This synthesis keeps their populations, measurement differences and uncertainty separate.", "scope": "Published aggregate outputs only. Discovery covers TCGA PanCancer Atlas gastric and breast tumour samples with copy-number calls. Evaluations examine separate public collections for descriptive contrast only, without treatment, outcome, or clinical HER2 status inference.", "units": [ "U-A1" ], "pairs": [ "QP-01", "QP-05" ], "sections": [ { "heading": "Question, data and method", "paragraphs": [ "The question asked whether co-amplification of selected distant loci among ERBB2-amplified tumours differs between selected gastric and breast collections. Discovery data comprised TCGA PanCancer Atlas bulk primary tumours: 438 gastric and 1,070 breast tumour samples with copy-number calls, retrieved 2026-09-28 via the cBioPortal public API using GISTIC 2.0 discrete calls (value 2 = high-level amplification; denominator = samples with CNA data). These counts represent bulk tumour sample accessions rather than deduplicated patient denominators, and do not represent clinical HER2 status by IHC/ISH. No treatment or outcome data were used." ], "units": [ "U-A1" ] }, { "heading": "Observed discovery result", "paragraphs": [ "In the TCGA material, ERBB2 high-level amplification occurred in 58/438 gastric (13.2%) and 123/1,070 breast (11.5%) tumour samples. Among ERBB2-amplified samples, co-amplification of EGFR, MET, FGFR2, KRAS or CCNE1 occurred in 27/58 gastric (46.6%) versus 9/123 breast (7.3%) samples. GRB7 and CDK12 share the ERBB2 amplicon and were kept outside this selected distant-locus endpoint. These are descriptive reported-call counts, not clinical HER2 diagnoses or treatment-response measurements." ], "units": [ "U-A1" ] }, { "heading": "Computational reproduction and two cohort evaluations", "paragraphs": [ "A separate implementation reproduced the recorded numerical result fields on the same named TCGA cohorts. Title, retrieval date and prose method metadata were outside that numerical comparison. Original raw-input hashes were not retained, so historical input byte identity remains unverified. This is computational reproduction by the internal team, not independent external-team or biological validation.", "CV-A1 used patient-deduplicated collections and supported the prespecified directional comparison: co-amplification occurred in 11/17 ERBB2-amplified gastric patients in the selected OncoSG collection versus 42/298 breast patients in METABRIC. The gastric publication also contained TCGA material; that discovery material was excluded from this evaluation. Independence of all upstream preprocessing was not established.", "CV-A3 evaluated a new EGC-MSK gastric collection against the same frozen METABRIC comparator. Its primary contrast was inconclusive: 3/26 gastric versus 42/298 breast amplified complete cases. The recorded risk difference was -2.56 percentage points, with a 95% interval from -11.29 to +15.23 points. This negative point estimate establishes neither an opposite direction nor equivalence. Six-gene complete cases were required and missing calls were not filled with zero. The minimum subgroup count was a guard, not a power calculation.", "The anatomically concordant 248-person gastric primary set was fixed before selected molecular retrieval. The original 280-person frame and three other prespecified sensitivity groups remain descriptive and do not replace the primary result. Both evaluations reuse the METABRIC comparator and are correlated; the second adds no new breast patient coverage. Assay platforms and cancer types remain confounded. No pooled effect is estimated here." ], "units": [ "U-A1" ] }, { "heading": "Limitations and next decisions", "paragraphs": [ "TCGA discovery counts refer to tumour samples; the later evaluations use selected patient-deduplicated cohorts. Recruitment, specimen definitions and measurement platforms were not made interchangeable. Small amplified gastric subgroups leave uncertainty, and donor overlap across differently anonymized studies cannot be fully excluded.", "The evaluation plans were locally fixed after earlier results were known and before their selected molecular retrieval. For CV-A3, an incidental whole-release aggregate had already been seen and disclosed. These are retrospective internal evaluations, not fully blinded or externally preregistered prospective studies.", "The next useful observation would come from a separately collected, adequately characterized cohort with compatible measurements and selection rules fixed before its outcomes are inspected. Any new estimate must retain prior inconclusive findings and account for comparator reuse. A genomic co-amplification pattern alone does not establish a resistance mechanism, drug sensitivity or treatment benefit." ], "units": [ "U-A1" ] } ], "comparison": [ { "units": [ "U-A1" ], "context": "ERBB2-amplified gastric versus breast contrast for distant-locus co-amplification in discovery and follow-up collections.", "reads": "TCGA sample counts differed; CV-A1 supported its patient-level directional comparison, while CV-A3 was inconclusive with the same reused breast comparator.", "boundary": "Discrete copy-number calls do not equal clinical HER2 status, and platform confounding, shared comparators, and small subgroups preclude causal or treatment generalization." } ], "changesMind": "A compatible separate-cohort evaluation with narrower uncertainty could revise the observational judgment. A source or implementation discrepancy could also require revision. Any change must account for population selection, measurement differences and comparator reuse; these descriptive comparisons cannot determine treatment benefit.", "next": [ "Assess source overlap, specimen definitions and gene coverage before selecting another cohort.", "Freeze any new selection and analysis rules before inspecting selected molecular outcomes, disclosing already known results.", "Keep descriptive genomic contrasts separate from randomized evidence about treatment effects." ] }, { "id": "RB-10", "program": "gastric", "asOf": "2026-09-30", "added": "2026-09-30", "by": "Gemini Flash3.8; Muse Spark1.3 review; Codex source reconciliation", "reviewedBy": "muse-spark-1.3", "title": "What the CLDN18 isoform comparison establishes", "summary": "This brief records an equal-length position-by-position comparison of canonical CLDN18 isoform A1 (P56856-1) and isoform A2 (P56856-2, CLDN18.2) and a numerical reproduction of the recorded outputs. It states measured differences, annotation boundaries and reproduction limits without drawing structural, binding or clinical inferences.", "scope": "Comparison of two 261-residue UniProt records and reproduction of eight recorded output fields. Topology is canonical annotation only. No binding, efficacy, diagnostic, or model-suitability inference is made from sequence identity or difference alone.", "units": [ "U-A3" ], "pairs": [ "QP-13", "QP-16" ], "sections": [ { "heading": "Analytical Question and Equal-Length Method", "paragraphs": [ "The recorded QP-13 question concerns whether a canonical CLDN18 record can stand in for CLDN18.2. Unit U-A3 addresses only the sequence component. Analysis A3 retrieved P56856-1 and P56856-2 on 2026-09-28 and compared the two 261-residue sequences at identical 1-based positions with no alignment inference. Topology and alternative-sequence annotation were read from P56856. Unequal lengths are incomparable under this method; no folding, epitope, affinity, or clinical measurement is made." ], "units": [ "U-A3" ] }, { "heading": "Measured Differences and Annotation Boundaries", "paragraphs": [ "Both records are 261 residues. Twenty-one positions differ across the measured span from residue 2 to residue 69, with identical sequence from residue 70 through 261. UniProt annotates an alternative sequence for A2 across residues 1 to 69, but residue 1 is identical, so annotation interval and measured span are distinct. Differences are reported as observed residue differences at corresponding sequence positions, not as acquired substitutions and not as a tested cancer mechanism.", "By canonical coordinates, residues 1 to 69 overlap cytoplasmic segment 1 to 6, transmembrane helix 7 to 27, and part of extracellular segment 28 to 80. That topology is annotated for canonical A1; whether it holds for A2 is not shown. The comparison therefore locates differences against canonical coordinates only and does not establish A2 topology, folding, epitope exposure, binding, or therapeutic response." ], "units": [ "U-A3" ] }, { "heading": "Computational Reproduction and Input Verification Limits", "paragraphs": [ "An independent Python implementation re-evaluated the same named pair against a freshly frozen snapshot. It ran 148 automated checks across eight fields covering lengths, positions, span, identity resumption, per-position differences, topology, alternative-sequence definition, and touched regions, with zero failed fields. This is numerical concordance of software outputs, not biological validation, and sequence difference alone is not proof of differential binding or response. No original raw snapshots accompanied the legacy artifact, so byte identity with original 2026-09-28 inputs is unverified." ], "units": [ "U-A3" ] }, { "heading": "What remains to be checked", "paragraphs": [ "The linked research judgments separate isoform identity, structural correspondence, antibody function and clinical assay criteria. The sequence calculation supports keeping the two records distinct. It does not itself measure their structural or functional interchangeability.", "Antibody contacts located after residue 70 would not by themselves justify substituting a canonical model for the other isoform. That use would require documented isoform and sequence identity, contact mapping and structural correspondence appropriate to the proposed analysis. Clinical assay concordance requires its own evidence. These are conditions for further review, not results produced by this sequence calculation." ], "units": [ "U-A3" ] } ], "comparison": [ { "units": [ "U-A3" ], "context": "Equal-length comparison of P56856-1 and P56856-2 with canonical P56856 topology and numerical reproduction against a frozen snapshot.", "reads": "Both 261 residues; 21 differing positions from residue 2 to 69; identical from residue 70 to 261; 148 software checks passed with zero failed fields and unverified original byte identity.", "boundary": "Primary-structure divergence relative to canonical coordinates only; does not establish A2 topology, folding, epitope exposure, binding, efficacy, or clinical concordance; numerical agreement is not biological validation." } ], "changesMind": "A verified source or implementation change could revise the sequence comparison. Structural or functional interpretations require directly relevant mapping and empirical evidence; sequence identity after residue 70 alone does not establish model interchangeability.", "next": [ "Retain the residue 70 onward identity and 2 to 69 difference span as sequence facts pending any justified structure mapping.", "Retain separate confirmation for isoform identity, structural correspondence, and assay concordance without merging criteria." ] }, { "id": "RB-11", "program": "gastric", "asOf": "2026-10-01", "title": "FGFR2b in gastric cancer: interim survival and later uncertainty", "summary": "Bemarituzumab plus mFOLFOX6 showed activity in FGFR2b-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma in the randomized phase 2 FIGHT and phase 3 FORTITUDE-101 trials. A synthesis must separate the formal success at the interim analysis, at which the full alpha was spent, from the later, descriptive attenuation; keep the efficacy denominators distinct from the as-treated safety denominators; and report bemarituzumab-associated corneal harm without treating the assays as interchangeable.", "scope": "Narrative synthesis of randomized evidence for bemarituzumab in advanced gastric or gastroesophageal junction adenocarcinoma. It does not provide practice recommendations or compare against chemoimmunotherapy.", "units": [ "U-FIGHT", "U-FORT101" ], "pairs": [ "QP-41" ], "sections": [ { "heading": "Trial transition and biomarker scope", "paragraphs": [ "FIGHT and FORTITUDE-101 tested first-line bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6 in HER2-non-positive advanced gastric or gastroesophageal junction adenocarcinoma. FIGHT was a randomized phase 2 trial permitting FGFR2b overexpression by immunohistochemistry, FGFR2 amplification in circulating tumor DNA, or both. FORTITUDE-101 was a separate randomized phase 3 trial selected by FGFR2b staining. Neither establishes that the two selection methods are interchangeable.", "Threshold handling differs by level. FIGHT evaluated FGFR2b 2+/3+ in at least 10% of tumor cells as prespecified exploratory. FORTITUDE-101 used that 10% cutoff for the prespecified primary efficacy population (N=324) while total enrollment included staining above 0% (N=547). Registry eligibility currently states 10% or more, differing from the abstract enrolled description; amendment history is unreconciled. Immunohistochemical overexpression is not interchangeable with FGFR2 amplification." ], "units": [ "U-FIGHT", "U-FORT101" ] }, { "heading": "Interim confirmation versus descriptive follow-up", "paragraphs": [ "FORTITUDE-101 crossed the overall survival efficacy boundary at the primary interim analysis with full alpha spent in the 10% or higher population (HR 0.61; P=0.005). Later follow-up was descriptive only and showed attenuation (HR 0.82, confidence interval including no difference). The later result is not a new formal failure test, but it leaves clinical uncertainty about durability.", "FIGHT primary report described progression-free survival as not statistically significant and the trial as exploratory (HR 0.68; P=0.073). That interpretation is distinct from the publicly attached primary analysis plan specifying one-sided 0.1 hierarchical testing of progression-free then overall survival and response. The plan document date alone does not establish fixation before data inspection. Final FIGHT follow-up stated no formal hypothesis testing was performed. P>0.05 alone is not used to label this exploratory trial a primary-endpoint failure." ], "units": [ "U-FIGHT", "U-FORT101" ] }, { "heading": "Bemarituzumab-associated corneal events and safety denominators", "paragraphs": [ "Safety is as-treated and distinct from efficacy. In the FORTITUDE-101 safety cohort (N=542), Grade 3 or higher treatment-emergent events were higher with bemarituzumab; the abstract attributes this treatment-emergent excess mainly to corneal events. That attribution is not extended to all safety increases including treatment-related events.", "FIGHT also reported more corneal events, including severe events, with bemarituzumab. Similar average trajectories in exploratory quality-of-life analyses do not establish equivalence or negate the ocular signal. These findings concern the studied drug and regimen; they do not establish a class-wide toxicity profile." ], "units": [ "U-FIGHT", "U-FORT101" ] }, { "heading": "Maturity and landscape boundaries", "paragraphs": [ "Maturity is unequal. FIGHT primary, final and quality-of-life reports are extended follow-up of one phase 2 trial, not independent replications. FORTITUDE-101 was reviewed here only as a conference abstract; a full manuscript and presentation were not reviewed for this record and the received registry record has no posted structured results.", "Neither trial compared bemarituzumab against contemporary chemoimmunotherapy, so no superiority over those regimens is established. Numerical efficacy for FORTITUDE-102 is unavailable here, so no efficacy inference or indirect comparison for bemarituzumab with checkpoint inhibition is drawn." ], "units": [ "U-FIGHT", "U-FORT101" ] } ], "comparison": [ { "units": [ "U-FIGHT" ], "context": "First-line HER2-non-positive advanced gastric/GEJ cancer; randomized phase 2", "reads": "Exploratory signal with descriptive final follow-up; no formal testing at final analysis", "boundary": "Follow-up reports belong to the same trial; the 10% cutoff was exploratory; corneal harm remains part of the result." }, { "units": [ "U-FORT101" ], "context": "First-line HER2-non-positive advanced gastric/GEJ cancer; randomized phase 3", "reads": "Primary interim survival boundary crossed with full alpha spent; later descriptive follow-up attenuated", "boundary": "Abstract-only review; unreconciled 10% versus above-0% enrollment descriptions; no chemoimmunotherapy comparison." } ], "changesMind": "Review of the full FORTITUDE-101 manuscript and reconciled protocol amendment history would clarify durability and enrollment cutoffs. Descriptive attenuation does not overturn the crossed interim boundary.", "next": [ "Seek and review the full FORTITUDE-101 report and presentation for survival and corneal-event resolution; neither was reviewed here.", "Reconcile registry and protocol records on above-0% versus 10%-or-higher enrollment.", "Track FORTITUDE-102 reporting without inferring efficacy from status." ], "added": "2026-10-01", "by": "Gemini Flash3.8; revised by Muse Spark1.3; source-checked and integrated by Codex (GPT-6)" }, { "id": "RB-12", "program": "breast", "asOf": "2026-10-01", "title": "First-line TNBC when immunotherapy is not an option", "summary": "A synthesis of ASCENT-03 and TROPION-Breast02 in previously untreated advanced triple-negative breast cancer when PD-1/PD-L1 inhibitor therapy is not an option. It reports PFS and OS results separately, gives the observed confidence intervals and notes that the safety reporting is not comparable.", "scope": "Narrative synthesis, not systematic review or treatment recommendation", "units": [ "U-ASCENT03", "U-TROPIONB02" ], "pairs": [ "QP-33" ], "sections": [ { "heading": "Population Defined by Immunotherapy Ineligibility", "paragraphs": [ "ASCENT-03 (NCT05382299) enrolled previously untreated locally advanced unresectable or metastatic triple-negative breast cancer. TROPION-Breast02 (NCT05374512) enrolled previously untreated locally recurrent inoperable or metastatic disease. Both randomized patients for whom PD-1 or PD-L1 inhibitor therapy was not an option. This synthesis uses primary abstracts, a protocol abstract and registry records; full-text publications were not reviewed.", "Ineligibility is not synonymous with PD-L1-negative status alone. ASCENT-03 enrolled tumors with PD-L1 combined positive score less than 10 and tumors with score 10 or higher when patients had previous anti-PD-(L)1 use or coexisting conditions precluding checkpoint inhibition. TROPION-Breast02 enrolled PD-L1-negative disease and PD-L1-positive disease with relapse after prior early-stage anti-PD-(L)1 therapy, comorbidities precluding therapy, or lack of regulatory access to pembrolizumab.", "The TROPION-Breast02 protocol publication (PMID 37526149) is design background for the same trial, not an independent study. Findings apply only to the defined not-a-candidate population and do not extend to unselected or immunotherapy-eligible populations." ], "units": [ "U-ASCENT03", "U-TROPIONB02" ] }, { "heading": "ASCENT-03: Sacituzumab Govitecan Progression-Free Survival", "paragraphs": [ "The international open-label phase 3 ASCENT-03 trial assigned patients 1:1 to sacituzumab govitecan or physician's choice chemotherapy with paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin. The primary endpoint was progression-free survival by blinded independent central review.", "Among 558 patients in the primary report, median progression-free survival was 9.7 months (95% CI, 8.1 to 11.1) with sacituzumab govitecan versus 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for progression or death 0.62; 95% CI, 0.50 to 0.77; P<0.001).", "Overall survival was a secondary endpoint with no numeric result reported in the supplied abstract, so no survival inference is made. The registry records actual enrollment of 623; this count is explicitly unreconciled at abstract level and is not claimed as a larger efficacy analysis.", "Adverse events of grade 3 or higher, not described as treatment-related in the abstract, occurred in 66% with sacituzumab govitecan and 62% with chemotherapy. Adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug occurred in 4% and 12%, respectively. Per-arm treated safety denominators were not reported. Linked correspondence items PMID 41885990 and PMID 41885991 were unread metadata only and are not treated as corrections." ], "units": [ "U-ASCENT03" ] }, { "heading": "TROPION-Breast02: Datopotamab Deruxtecan PFS and OS", "paragraphs": [ "The open-label phase 3 TROPION-Breast02 trial randomized 644 patients 1:1 to datopotamab deruxtecan (n=323) or investigator's choice chemotherapy (n=321; paclitaxel, nab-paclitaxel, carboplatin, capecitabine, or eribulin mesylate). Dual primary endpoints were progression-free survival by blinded independent central review per RECIST 1.1 and overall survival. Efficacy was in the intention-to-treat population.", "Median progression-free survival was 10.8 months (95% CI, 8.6 to 13.0) versus 5.6 months (95% CI, 5.0 to 7.0), hazard ratio 0.57 (99% CI, 0.44 to 0.73; P<0.0001). Median overall survival was 23.7 months (95% CI, 19.8 to 25.6) versus 18.7 months (95% CI, 16.0 to 21.8), hazard ratio 0.79 (95.01% CI, 0.64 to 0.98; P=0.029). Confidence intervals are reported as observed without alteration.", "Treatment-related adverse events of grade 3 or higher as reported were 105 patients (33%) with datopotamab deruxtecan and 89 patients (29%) with chemotherapy. Treatment-related adverse events led to discontinuation in 14 patients (4%) and 23 patients (7%), respectively. There were no treatment-related deaths in either arm, which does not imply zero all-cause mortality. Exact treated safety denominators were not stated and were not derived from randomized counts." ], "units": [ "U-TROPIONB02" ] }, { "heading": "Boundaries for Interpretation", "paragraphs": [ "The control regimens were not identical, and endpoint structures differ. TROPION-Breast02 reported statistically significant intention-to-treat progression-free survival and overall survival as dual primary endpoints with the observed intervals above. ASCENT-03 reported significant blinded central progression-free survival as the primary endpoint, with overall survival as a secondary endpoint without numeric results in the supplied abstract.", "The available abstracts do not support a direct comparison of toxicity. ASCENT-03 reported adverse events not described as treatment-related, while TROPION-Breast02 reported treatment-related adverse events. Neither abstract supplied exact treated safety denominators. These separate trials do not estimate a drug-versus-drug effect: eligibility, control regimens and endpoint structures differ. Comparing their hazard ratios or medians cannot establish drug superiority or a preferred treatment sequence.", "This synthesis claims no clinical recommendation and no independent research-team validation. Review of full-text reports, reconciliation of 558 versus 623 in ASCENT-03, mature numeric overall survival for ASCENT-03, or head-to-head randomization would warrant an update." ], "units": [ "U-ASCENT03", "U-TROPIONB02" ] } ], "comparison": [ { "units": [ "U-ASCENT03", "U-TROPIONB02" ], "context": "Efficacy endpoints and observed intervals", "reads": "ASCENT-03: median PFS 9.7 vs 6.9 months, stratified HR 0.62 (95% CI, 0.50-0.77; P<0.001); ORR 48% vs 46%; OS secondary with no numeric result in abstract. TROPION-Breast02: median PFS 10.8 vs 5.6 months, HR 0.57 (99% CI, 0.44-0.73; P<0.0001); median OS 23.7 vs 18.7 months, HR 0.79 (95.01% CI, 0.64-0.98; P=0.029).", "boundary": "These separate trials do not estimate a drug-versus-drug effect. Eligibility, control regimens and endpoint structures differ; comparing their reported effect sizes cannot establish drug superiority." }, { "units": [ "U-ASCENT03", "U-TROPIONB02" ], "context": "Safety reporting and denominators", "reads": "ASCENT-03: grade >=3 adverse events, not described as treatment-related, 66% vs 62%; adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug in 4% and 12%, respectively. TROPION-Breast02: grade >=3 treatment-related adverse events in 105 (33%) vs 89 (29%); treatment-related discontinuation in 14 (4%) vs 23 (7%); no treatment-related deaths.", "boundary": "Toxicity cannot be compared directly due to different attribution (adverse events vs treatment-related adverse events). No treatment-related deaths does not equal zero all-cause mortality. Neither abstract gave exact treated safety denominators." }, { "units": [ "U-ASCENT03", "U-TROPIONB02" ], "context": "Target population", "reads": "Both enrolled previously untreated advanced TNBC when immunotherapy was not an option, including PD-L1-negative disease and PD-L1-positive disease with prior early-stage checkpoint exposure, contraindicating comorbidity, and for TROPION-Breast02 lack of regulatory access.", "boundary": "Ineligibility must not be equated with PD-L1 negativity alone. Abstract data do not support subgroup-specific efficacy by ineligibility reason or sequencing advice." } ], "changesMind": "Full-text review of both trials, formal reconciliation of ASCENT-03 558 versus registry 623, mature numeric ASCENT-03 overall survival, or head-to-head randomization would warrant updating this synthesis.", "next": [ "Review the ASCENT-03 full text and dated registry/protocol history to investigate the 558 versus 623 discrepancy, and check for numerical overall-survival reporting.", "Review full-text safety tables for exact treated denominators and all-cause mortality for both trials.", "Track efficacy by specific ineligibility reason without assuming benefit or lack of benefit per subgroup." ], "by": "Gemini Flash3.8; revised by Muse Spark1.3; source-checked and integrated by Codex (GPT-6)", "added": "2026-10-01" }, { "id": "RB-13", "program": "gxb", "asOf": "2026-10-01", "title": "What Pathologic Response Can Establish", "summary": "Four gastric and breast cancer trials show why pathologic response must be read in light of trial design, surgical denominators, survival follow-up and safety. Response at surgery cannot measure the effect of treatment given afterward.", "scope": "Public primary abstracts and registry records for four neoadjuvant or perioperative trials in gastric/gastroesophageal junction and breast cancer. Full texts were not reviewed; no pooled efficacy comparison or new patient analysis.", "units": [ "U-DRAGONIV", "U-NEONIPIGA", "U-DB11", "U-NeoPACT" ], "pairs": [ "QP-31" ], "sections": [ { "heading": "Response within each trial", "paragraphs": [ "Randomized comparisons and single-arm interventional cohorts answer different questions, and pathologic complete response (pCR) definitions differ by trial. In DRAGON IV/CAP 05, perioperative SOXRC—camrelizumab plus low-dose rivoceranib and SOX—was compared with SOX alone in locally advanced gastric or gastroesophageal junction adenocarcinoma. Among the first 360 randomized patients with opportunity for surgery under per-protocol reporting (180 per group), pCR was 18.3% (95% CI, 13.0 to 24.8) versus 5.0% (95% CI, 2.3 to 9.3), source-reported difference 13.7 percentage points (95% CI, 7.2 to 20.1; one-sided P<.0001). In DESTINY-Breast11, neoadjuvant T-DXd-THP versus ddAC-THP in high-risk HER2-positive early breast cancer yielded pCR (ypT0/is ypN0, intention-to-treat) 67.3% (n=216/321) versus 56.3% (n=180/320), reported difference 11.2 percentage points (95% CI, 4.0 to 18.3; P=0.003); T-DXd alone yielded 43.0% (n=123/286). Both contrasts are retained as reported without inferring adjustment models. NEONIPIGA (pT0N0) and NeoPACT (no invasive tumor in breast and axilla) are single-arm interventional studies and therefore describe activity without comparative efficacy. A response assessed at surgery cannot be an outcome of postoperative treatment." ], "units": [ "U-DRAGONIV", "U-DB11", "U-NEONIPIGA", "U-NeoPACT" ] }, { "heading": "Who enters the denominator", "paragraphs": [ "Denominators determine what response rates mean. DRAGON IV reports the first 360 patients with a surgery opportunity; registry enrollment is an estimated 580, a different reporting scope. The abstract does not label the 360-patient set as an interim analysis. DESTINY-Breast11 uses randomized intention-to-treat denominators. NEONIPIGA treated 32 patients, including one protocol-ineligible patient with baseline metastasis; 29 underwent surgery with R0 resection, and pCR was 17/29 (58.6%; 90% CI, 41.8 to 74.1). Three non-operated patients had complete endoscopic responses with tumor-free biopsies, which does not establish that resection can be omitted. NeoPACT analyzed 115 eligible patients for pCR 58% (95% CI, 48% to 67%), while the registry records 120 actual enrolled patients, an explicitly unresolved discrepancy." ], "units": [ "U-DRAGONIV", "U-DB11", "U-NEONIPIGA", "U-NeoPACT" ] }, { "heading": "Response and survival answer different questions", "paragraphs": [ "DRAGON IV lists event-free survival (EFS) as a co-primary endpoint, but this abstract does not report EFS; therefore no recurrence or survival conclusion follows from the pCR difference here, and full text was not reviewed to seek it. DESTINY-Breast11 reports secondary EFS at 4.5% maturity with hazard ratio 0.56 (95% CI, 0.26 to 1.17), a confidence interval crossing unity that does not establish survival benefit; even a statistically significant EFS difference alone would not validate pCR as a surrogate. NEONIPIGA, with median follow-up 14.9 months (95% CI, 10.6 to 17.6), documents no relapse with one death without relapse, a descriptive observation in a single group. NeoPACT estimates 3-year EFS 86% overall, 98% with pCR versus 68% with residual disease; because pCR status is defined after preoperative therapy, this stratification is a post-treatment observational association, not causal evidence that achieving pCR prolongs survival or that postoperative components can be separated. When both treatment phases differ by assignment, survival comparisons evaluate the whole strategy; QP-31 keeps the contribution of each phase unresolved." ], "units": [ "U-DRAGONIV", "U-DB11", "U-NEONIPIGA", "U-NeoPACT" ] }, { "heading": "Safety belongs beside response", "paragraphs": [ "These comparisons do not isolate each component’s incremental toxicity. DRAGON IV reports neoadjuvant grade ≥3 treatment-related adverse events 34% versus 17% and surgical complications 27% versus 33% for SOXRC versus SOX; enrollment in the third arm SOXR (high-dose rivoceranib plus SOX) was stopped after Independent Data Monitoring Committee review of safety data from the first 103 patients randomized across all three arms, not 103 in SOXR alone. In the order T-DXd alone, T-DXd-THP and ddAC-THP, DESTINY-Breast11 reports grade ≥3 adverse events, not restricted to treatment-related events, of 22.6% (n=64), 37.5% (n=120), and 55.8% (n=174), adjudicated drug-related interstitial lung disease/pneumonitis 4.9%, 4.4%, and 5.1%, and treatment-related deaths 0.3% (n=1, T-DXd-THP) and 0.6% (n=2, ddAC-THP); percentages use the safety analysis set whose denominators were not reported in the abstract and are not inferred from intention-to-treat, and T-DXd-alone closure followed IDMC recommendation with no reason stated in the abstract. NEONIPIGA reports neoadjuvant grade 3/4 treatment-related events 19% (6/32) with surgical morbidity 55% including one postoperative death; NeoPACT reports grade ≥3 immune-mediated events 3.5% without an overall severe-toxicity rate in the abstract." ], "units": [ "U-DRAGONIV", "U-DB11", "U-NEONIPIGA", "U-NeoPACT" ] } ], "comparison": [ { "units": [ "U-DRAGONIV", "U-DB11" ], "context": "Randomized absolute pCR contrasts in phase III trials", "reads": "DRAGON IV SOXRC 18.3% vs SOX 5.0%, reported difference 13.7 points (95% CI 7.2-20.1); DB11 T-DXd-THP 67.3% vs ddAC-THP 56.3%, reported difference 11.2 points (95% CI 4.0-18.3).", "boundary": "Abstracts only; full texts not reviewed. Contrasts retained as published without inferring adjustment models." }, { "units": [ "U-NEONIPIGA", "U-NeoPACT" ], "context": "Denominator definition in single-arm interventional trials", "reads": "NEONIPIGA pCR 17/29 operated (58.6%; 90% CI 41.8-74.1) of 32 treated; NeoPACT pCR 58% (95% CI 48-67) in 115 eligible vs 120 registry-enrolled, unresolved.", "boundary": "Abstracts plus registries only. Descriptive rates do not establish comparative efficacy." }, { "units": [ "U-DRAGONIV", "U-DB11", "U-NeoPACT" ], "context": "EFS reporting, maturity, and post-treatment stratification", "reads": "DRAGON IV EFS not reported in this abstract; DB11 EFS HR 0.56 (95% CI 0.26-1.17) at 4.5% maturity, crossing unity; NeoPACT 98% vs 68% by pCR status is post-treatment association, not causal.", "boundary": "Abstracts only. pCR differences do not validate surrogacy; EFS significance alone would not validate surrogacy." }, { "units": [ "U-DRAGONIV", "U-NEONIPIGA", "U-DB11" ], "context": "Severe toxicities, mortality, and arm closures", "reads": "DRAGON IV grade ≥3 neoadjuvant TRAEs: 34% vs 17%; SOXR enrollment stopped after safety review of 103 patients across all three arms. DESTINY-Breast11 grade ≥3 AEs: 37.5% with T-DXd-THP vs 55.8% with ddAC-THP; treatment-related deaths: one vs two. NEONIPIGA: 19% grade 3/4 neoadjuvant TRAEs, 55% surgical morbidity, one postoperative death.", "boundary": "DB11 percentages use safety set, not inferred from ITT. AE vs TRAE retained as reported." } ], "changesMind": "Interpretation would change with mature randomized EFS/OS showing concordant survival benefit alongside the reported pCR differences, which would support clinical relevance without alone proving surrogacy; randomized contribution-design or de-escalation data separating preoperative from postoperative effects would change the QP-31 hold on phase-specific contributions; and complete reconciled denominators with full safety sets would change precision judgments. Without such evidence, pCR remains a preoperative response measure that does not establish survival benefit or separable phase contributions.", "next": [ "Audit future DRAGON IV publications for mature EFS/OS to test whether the 13.7-point pCR difference corresponds to longitudinal benefit of the whole perioperative strategy.", "Track mature DB11 EFS beyond 4.5% maturity to reassess the HR 0.56 signal without inferring surrogacy from pCR alone.", "Reconcile NeoPACT 115 eligible versus 120 registry-enrolled counts without closing the discrepancy from abstracts alone.", "Monitor longer NEONIPIGA follow-up for late relapse, retaining that endoscopic response does not establish that surgery can be omitted." ], "by": "Gemini Flash3.8; revised by Muse Spark1.3; source-checked and integrated by Codex (GPT-6)", "added": "2026-10-01" } ], "files": [ { "id": "RF-G1", "program": "gastric", "pair": "QP-06", "target": "ERBB2", "dossier": "SD-ERBB2", "analyses": [], "resistance": [ "RS-HER2LOSS" ], "why": "공개 근거와 데이터 접근성을 확인한 결과, 위암 쪽에서 가장 근거가 촘촘한 내성 질문이다. 재생검 비율과 등록 기준 문장이 모두 원문으로 확인된다.", "hypothesis": "1차 항HER2 치료 뒤 HER2 양성을 잃은 종양이 섞이면 2차 치료 비교의 효과 크기가 희석된다." }, { "id": "RF-B1", "program": "breast", "pair": "QP-08", "target": "ESR1", "dossier": "SD-ESR1", "analyses": [ "A2", "A5" ], "resistance": [ "RS-ESR1", "RS-MAPK" ], "why": "횡단 비교와 같은 환자의 짝지은 관찰, 별도 수집 코호트의 판단 불가 결과를 연결한 ESR1 연구 파일이다. 관찰과 혈액 검사 기반 치료 교체 시험은 서로 다른 질문으로 관리한다.", "hypothesis": "조직의 ESR1 변이 검출 양상은 치료 교체 전략을 연구할 배경이지만, 그 전략의 환자 결과는 해당 무작위 비교와 후속 보고로 별도로 판단해야 한다." }, { "id": "RF-X1", "program": "gxb", "pair": "QP-01", "target": "ERBB2", "dossier": "SD-ERBB2", "analyses": [ "A1" ], "resistance": [ "RS-COAMP" ], "why": "두 암종을 같은 표적으로 잇는 비교 파일이다. 성공과 실패가 모두 3상으로 남아 있어 이식 가능성을 근거로 따질 수 있다.", "hypothesis": "위암의 ERBB2 증폭 종양은 다른 수용체·세포주기 유전자의 공동 변화가 잦아, 유방암에서 통한 일부 약제가 위암에서 통하지 않는다." }, { "id": "RF-C1", "program": "colorectal", "pair": "QP-24", "target": null, "dossier": null, "analyses": [], "resistance": [], "why": "위암·유방암의 잔존 질환 연구를 해석할 비교 파일이다. 결장암의 검사 기반 무작위 관리 전략과 다른 암종의 예후·개입 근거를 구분한다.", "hypothesis": "잔존 신호를 검출해도 실제 개입 시점과 치료의 효과가 확보되지 않으면 환자 결과 개선으로 이어지지 않을 수 있다.", "by": "Codex (GPT-6)", "added": "2026-09-28" } ], "resistance": [ { "id": "RS-HER2LOSS", "name": "Loss of HER2 positivity after trastuzumab", "program": "gastric", "target": "ERBB2", "context": "After first-line trastuzumab-containing therapy", "subtype": "G-HER2", "route": "Tumours re-biopsied at progression no longer meet HER2-positive criteria in a sizeable fraction; within-tumour heterogeneity rises.", "units": [ "U-GASTHER3", "U-HER2loss16", "U-Janjigian18" ], "consequence": "Second-line comparisons that do not re-measure HER2 mix two populations (QP-06).", "pairs": [ "QP-06" ] }, { "id": "RS-COAMP", "name": "Co-alteration alongside ERBB2 amplification", "program": "gxb", "target": "ERBB2", "context": "ERBB2-amplified tumours", "subtype": "G-HER2", "route": "RTK, RAS and PI3K co-alterations were associated with intrinsic or acquired trastuzumab resistance in one esophagogastric cohort; A1 counts how often such co-amplification occurs in each cancer.", "units": [ "U-Janjigian18", "U-A1" ], "consequence": "A candidate explanation for why HER2 results do not transfer between the two cancers (QP-01) — a hypothesis, not a finding.", "pairs": [ "QP-01" ] }, { "id": "RS-ESR1", "name": "Acquired ESR1 ligand-binding-domain mutations", "program": "breast", "target": "ESR1", "context": "During aromatase-inhibitor-based therapy", "subtype": "B-HRPOS", "route": "Mutations such as D538G and Y537S are far more frequent in metastatic than primary HR+/HER2− samples (A2) and stabilise the AF-2-binding conformation (preclinical).", "units": [ "U-A2", "U-Fanning16", "U-EMERALD", "U-PADA1" ], "consequence": "Selects patients for newer ER antagonists and degraders; the timing question is QP-08.", "pairs": [ "QP-08" ] }, { "id": "RS-MAPK", "name": "MAPK and ER-machinery alterations", "program": "breast", "target": "ESR1", "context": "After hormonal therapy", "subtype": "B-HRPOS", "route": "Alterations in MAPK pathway genes and the ER transcriptional machinery were enriched in treated tumours, mutually exclusive with ESR1 mutations, and linked to shorter response to subsequent hormonal therapy.", "units": [ "U-Razavi18" ], "consequence": "A second resistance route that an ESR1-only test would miss.", "pairs": [] }, { "id": "RS-CDK46-POST", "name": "Progression on a CDK4/6 inhibitor with endocrine therapy", "program": "breast", "target": "CDK4/6", "context": "After progression on first-line CDK4/6 inhibitor plus endocrine therapy", "subtype": "B-HRPOS", "route": "Randomized trials after progression split by what was changed: switching the endocrine partner together with a different CDK inhibitor (abemaciclib after mostly palbociclib; ribociclib with switched endocrine therapy) prolonged PFS, while continuing or rechallenging palbociclib did not show a significant benefit.", "units": [ "U-postMONARCH", "U-MAINTAIN", "U-PACE", "U-PALMIRA" ], "consequence": "Resistance to one CDK4/6 inhibitor is not shown to be class-wide, but the trials do not separate the drug change from the endocrine change (QP-35).", "pairs": [ "QP-35" ] }, { "id": "RS-FAH-CDK9", "name": "Nuclear FAH–CDK9 axis under CDK4/6 inhibition", "program": "breast", "target": "CDK4/6", "context": "Preclinical models of resistance to CDK4/6 inhibition", "subtype": "B-HRPOS", "route": "In breast cancer models, FAH moved into the nucleus during CDK4/6 inhibition and interacted with CDK9; CDK9 inhibition reversed FAH-mediated resistance in the tested models, and nuclear FAH was enriched in relapsed tumours.", "units": [ "U-FAHCDK9" ], "consequence": "A mechanistic hypothesis only: no validated biomarker, patient selection rule or clinical benefit (QP-45).", "pairs": [ "QP-45" ] }, { "id": "RS-PI3K-ENDO", "name": "PI3K/AKT pathway activity in endocrine-resistant disease", "program": "breast", "target": "PIK3CA", "context": "Relapse during or soon after endocrine therapy", "subtype": "B-HRPOS", "route": "Adding an AKT inhibitor to fulvestrant, or a PI3Kα inhibitor to palbociclib and fulvestrant in PIK3CA-mutated early relapse, prolonged PFS; the final capivasertib overall-survival analysis was not significant.", "units": [ "U-CAP291", "U-INAVO120" ], "consequence": "Pathway-directed add-ons delay progression in selected disease; a survival effect is not established for capivasertib, and the two trials select different populations.", "pairs": [] }, { "id": "RS-PARP-EFFLUX", "name": "Drug efflux after PARP inhibition (model)", "program": "breast", "target": "PARP1", "context": "BRCA1-deficient mouse mammary tumours treated with a PARP inhibitor", "subtype": null, "route": "Tumours that initially responded later became resistant with increased expression of P-glycoprotein efflux genes; combining the PARP inhibitor with platinum prolonged recurrence-free and overall survival in the model.", "units": [ "U-PARPRottenberg08" ], "consequence": "One mouse-model route; it does not establish how resistance arises in patients with germline BRCA1/2 variants.", "pairs": [] }, { "id": "RS-ADC-SEQ", "name": "Short benefit from a second antibody–drug conjugate", "program": "breast", "target": "ERBB2", "context": "HER2-low metastatic disease treated with T-DXd and sacituzumab govitecan in sequence", "subtype": null, "route": "In a selected retrospective cohort that received both ADCs, progression-free survival on the second ADC was short in either order, consistent with cross-resistance through the shared topoisomerase-I payload class or through treatment history.", "units": [ "U-ADCLow" ], "consequence": "Retrospective and selected: order effects and mechanism are not established (QP-11).", "pairs": [ "QP-11" ] }, { "id": "RS-RAM-BEYOND", "name": "VEGFR2 blockade continued beyond progression", "program": "gastric", "target": "KDR", "context": "Third or later line after progression on ramucirumab-containing chemotherapy", "subtype": null, "route": "Continuing ramucirumab with irinotecan after progression improved progression-free survival but did not significantly improve overall survival.", "units": [ "U-RINDBeRG" ], "consequence": "Resistance to VEGFR2 blockade is not overcome in a way that changes survival in this trial; the result is not proof of zero effect (QP-04).", "pairs": [ "QP-04" ] } ], "ledger": [ { "date": "2026-10-05", "kind": "fetch", "what": "AlphaFold DB models for the ESMO 2024 NGS gene tables", "detail": "The owner chose guideline biomarkers as the scope for structure models. Genes named in tables 1, 3, 4 and 11 of the ESMO Precision Medicine Working Group 2024 recommendations (tumour-agnostic, breast, colorectal, thyroid) were listed with their source; the nine without a model (NTRK1, NTRK2, NTRK3, FGFR1, FGFR3, PALB2, KRAS, NRAS, POLE) were fetched. BRCA2 has no single AlphaFold DB model. Gastric cancer sits in a supplementary table not yet read. These nine are marked as not linked to evidence.", "by": "data/curated/panel-esmo2024.json; scripts/fetch-sources.mjs proteins; scripts/fetch-models.mjs" }, { "date": "2026-10-05", "kind": "fetch", "what": "AlphaFold DB models for RET, VEGFA, CTLA4, BRAF, BRCA1, PTEN and TP53", "detail": "Proteins named in evidence text as drug targets (selpercatinib, bevacizumab, ipilimumab, BRAF inhibition) or biomarkers (germline BRCA1, PTEN, TP53) had no structure model. The seven canonical entries were added to the identifier list and fetched with coordinates, per-residue confidence and PAE. They are not registered as evidence targets. Their RCSB experimental entry counts were fetched in the same pass.", "by": "scripts/fetch-sources.mjs proteins; scripts/fetch-models.mjs" }, { "date": "2026-10-03", "kind": "fetch", "what": "AlphaFold DB models for AKT2, AKT3, PARP2 and MTOR", "detail": "The AKT card (pan-AKT capivasertib) showed AKT1 only, the PARP1/2 card PARP1 only, and everolimus had no target model. The four canonical entries were added to the identifier list and fetched with coordinates, per-residue confidence and PAE.", "by": "scripts/fetch-sources.mjs proteins; scripts/fetch-models.mjs" }, { "date": "2026-10-03", "kind": "check", "what": "First dated result check for PR-001", "detail": "Registry record and two PubMed searches re-fetched with receipts; no eligible event-free-survival result found. The forecast stays awaiting result and the frozen v1 is unchanged.", "by": "docs/predictions/PR-001-check-2026-10-03.json" }, { "date": "2026-10-03", "kind": "forecast", "what": "PR-001 frozen: DRAGON IV event-free survival direction", "detail": "The first forecast written before its result: question, population, comparator, endpoint, report-selection rule, basis, counterarguments and comparison rules, pinned by hash. No probability or effect size was given.", "by": "docs/predictions/PR-001.v1.json; scripts/prediction-records.mjs" }, { "date": "2026-09-30", "kind": "analysis", "what": "External-cohort evaluations CV-A1, CV-A2 and CV-A3", "detail": "Prespecified descriptive evaluations of the A1 and A2 signals in separately collected patient cohorts. One supported the original direction and two were inconclusive; none was a biological experiment or a predictive-model validation.", "by": "data/cohort-validations/2026-09-30; scripts/cohort-records.mjs" }, { "date": "2026-09-30", "kind": "analysis", "what": "A5 paired ESR1 analysis executed", "detail": "Paired primary and metastatic specimens from the same patients, run from a locked plan with hashed inputs, code and outputs, then audited.", "by": "scripts/run-paired-mutation.py; docs/A5-PLAN-2026-09-30.json" }, { "date": "2026-09-30", "kind": "check", "what": "Computational reproduction of A1 and A3", "detail": "Separate Python implementations agree with the saved scientific outputs: A1 84/84 checks; A3 148/148 object/leaf checks. Two unique analyses reproduced, no independent biological validation. Original historical input byte identity is unverified; newly fetched official inputs are frozen.", "by": "scripts/reproduce-a1.py; scripts/reproduce-a3.py; scripts/research-records.mjs" }, { "date": "2026-09-30", "kind": "fetch", "what": "DepMap A4 inputs partially received", "detail": "Pinned 24Q4 Public v1 metadata and license verified. Model.csv alone received and checked against the official checksum; four required files remain missing. Plan is a draft, no outcomes inspected or regression executed.", "by": "scripts/fetch-depmap-a4.py; data/analyses/inputs/A4/access-report.json" }, { "date": "2026-09-28", "kind": "fetch", "what": "Re-fetched every cited identifier from its source", "detail": "53 trials (ClinicalTrials.gov API v2), 83 papers (PubMed E-utilities), 13 proteins (UniProt, AlphaFold DB, RCSB search), structure entries (RCSB Data API).", "by": "scripts/fetch-sources.mjs" }, { "date": "2026-09-28", "kind": "correction", "what": "Wrong registry number for VERITAC-2", "detail": "NCT05909397 was first entered for VERITAC-2; the registry lists it as VERITAC-3. Replaced with NCT05654623, whose record reads VERITAC-2.", "by": "Evidence Curator check against the registry acronym" }, { "date": "2026-09-28", "kind": "correction", "what": "Two literature searches matched unrelated papers", "detail": "The first queries for GATSBY and RAINFALL returned “The academic Great Gatsby Curve” and “Rainfall events and adverse health outcomes”. Queries were narrowed to title terms and the correct papers pinned by PMID.", "by": "scripts/fetch-sources.mjs, second pass" }, { "date": "2026-09-28", "kind": "correction", "what": "Default CLDN18 model is not CLDN18.2", "detail": "The default AlphaFold entry is isoform A1. The isoform A2 (CLDN18.2) entry exists and replaces it; analysis A3 records where the isoforms differ.", "by": "scripts/run-analyses.mjs (A3)" }, { "date": "2026-09-28", "kind": "check", "what": "Post-progression HER2 re-confirmation in two trials", "detail": "DESTINY-Gastric04 eligibility (registry text) and DESTINY-Gastric02 methods (abstract) both require HER2 positivity confirmed on a biopsy taken after progression.", "by": "data/sources/trials-eligibility.json, papers.json" }, { "date": "2026-09-28", "kind": "analysis", "what": "Ran A1, A2, A3", "detail": "ERBB2 co-amplification (TCGA gastric vs breast); ESR1 and PIK3CA in primary vs metastatic samples; CLDN18 isoform sequence comparison.", "by": "scripts/run-analyses.mjs" }, { "date": "2026-09-28", "kind": "check", "what": "Retraction, correction and duplicate check", "detail": "No retraction or expression of concern among 83 papers. Eight correction notices on seven papers; none has an abstract, so whether they touch a cited number is unreviewed. No duplicate identifiers. Every internal reference resolves.", "by": "scripts/check-integrity.mjs" }, { "date": "2026-09-28", "kind": "fetch", "what": "Benchmark indicators for 30 institutions and RISCON Labs", "detail": "Trial and publication counts with published queries; a self-test confirmed the results-posted filter narrows counts before it was used.", "by": "scripts/fetch-benchmarks.mjs, fetch-representatives.mjs" } ], "collabLinks": [ { "unit": "U-ToGA", "label": "ToGA", "lead": "Hoffmann-La Roche", "leadIds": [ "roche" ], "collaborators": [ "Chugai Pharmaceutical" ], "collabIds": [], "outside": [ "Chugai Pharmaceutical" ] }, { "unit": "U-DG01", "label": "DESTINY-Gastric01", "lead": "Daiichi Sankyo Co., Ltd.", "leadIds": [ "daiichi" ], "collaborators": [ "AstraZeneca" ], "collabIds": [ "astrazeneca" ], "outside": [] }, { "unit": "U-DG02", "label": "DESTINY-Gastric02", "lead": "Daiichi Sankyo", "leadIds": [ "daiichi" ], "collaborators": [ "AstraZeneca" ], "collabIds": [ "astrazeneca" ], "outside": [] }, { 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Surgeons", "Cancer and Leukemia Group B", "NSABP Foundation Inc", "NCIC Clinical Trials Group", "North Central Cancer Treatment Group", "SWOG Cancer Research Network" ] }, { "unit": "U-MINDACT", "label": "MINDACT", "lead": "European Organisation for Research and Treatment of Cancer - EORTC", "leadIds": [], "collaborators": [ "Agendia", "Breast International Group", "Roche Pharma AG", "Novartis", "Sanofi" ], "collabIds": [ "novartis" ], "outside": [ "Agendia", "Breast International Group", "Roche Pharma AG", "Sanofi" ] }, { "unit": "U-SALSA", "label": "ABCSG-16/SALSA", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-DAISY", "label": "DAISY", "lead": "UNICANCER", "leadIds": [], "collaborators": [ "Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company" ], "collabIds": [ "daiichi" ], "outside": [] }, { "unit": "U-AVAGAST", "label": "AVAGAST", "lead": "Genentech, Inc.", "leadIds": [ "roche" ], "collaborators": [ "Hoffmann-La Roche", "Chugai Pharmaceutical" ], "collabIds": [ "roche" ], "outside": [ "Chugai Pharmaceutical" ] }, { "unit": "U-DB08", "label": "DESTINY-Breast08", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [ "Daiichi Sankyo Co., Ltd.", "Daiichi Sankyo Company, Limited" ], "collabIds": [ "daiichi", "daiichi" ], "outside": [] }, { "unit": "U-OlympiAD", "label": "OlympiAD · olaparib in germline-BRCA metastatic breast cancer", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [ "Myriad Genetic Laboratories, Inc.", "Merck Sharp & Dohme LLC" ], "collabIds": [ "msd" ], "outside": [ "Myriad Genetic Laboratories, Inc." ] }, { "unit": "U-TROPIONB02", "label": "TROPION-Breast02", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [ "Daiichi Sankyo" ], "collabIds": [ "daiichi" ], "outside": [] }, { "unit": "U-DB11", "label": "DESTINY-Breast11 · neoadjuvant HER2 regimen comparison", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [ "Daiichi Sankyo" ], "collabIds": [ "daiichi" ], "outside": [] }, { "unit": "U-NeoPACT", "label": "NeoPACT · single-arm anthracycline-free chemoimmunotherapy", "lead": "University of Kansas Medical Center", "leadIds": [], "collaborators": [ "Merck Sharp & Dohme LLC" ], "collabIds": [ "msd" ], "outside": [] }, { "unit": "U-evERA", "label": "evERA Breast Cancer", "lead": "Genentech, Inc.", "leadIds": [ "roche" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-MOUNTAINEER", "label": "MOUNTAINEER · tucatinib plus trastuzumab in HER2-positive colorectal cancer", "lead": "Seagen Inc.", "leadIds": [], "collaborators": [ "National Cancer Institute (NCI)", "Academic and Community Cancer Research United" ], "collabIds": [ "nci-us" ], "outside": [ "Academic and Community Cancer Research United" ] }, { "unit": "U-DCRC01", "label": "DESTINY-CRC01 · trastuzumab deruxtecan by HER2 expression level in colorectal cancer", "lead": "Daiichi Sankyo Co., Ltd.", "leadIds": [ "daiichi" ], "collaborators": [ "Daiichi Sankyo", "AstraZeneca" ], "collabIds": [ "daiichi", "astrazeneca" ], "outside": [] }, { "unit": "U-BEACON", "label": "BEACON CRC · encorafenib plus cetuximab in BRAF V600E colorectal cancer", "lead": "Pfizer", "leadIds": [ "pfizer" ], "collaborators": [ "Merck KGaA, Darmstadt, Germany", "Pierre Fabre Medicament", "Ono Pharmaceutical Co., Ltd." ], "collabIds": [], "outside": [ "Merck KGaA, Darmstadt, Germany", "Pierre Fabre Medicament", "Ono Pharmaceutical Co., Ltd." ] }, { "unit": "U-KN355", "label": "KEYNOTE-355 · pembrolizumab plus chemotherapy by PD-L1 score", "lead": "Merck Sharp & Dohme LLC", "leadIds": [ "msd" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-ML2", "label": "MONALEESA-2 · first-line ribociclib plus letrozole", "lead": "Novartis Pharmaceuticals", "leadIds": [ "novartis" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-DB02", "label": "DESTINY-Breast02", "lead": "Daiichi Sankyo", "leadIds": [ "daiichi" ], "collaborators": [ "Daiichi Sankyo Co., Ltd.", "AstraZeneca" ], "collabIds": [ "daiichi", "astrazeneca" ], "outside": [] }, { "unit": "U-OPRA", "label": "OPRA · watch-and-wait after total neoadjuvant therapy", "lead": "Memorial Sloan Kettering Cancer Center", "leadIds": [ "mskcc" ], "collaborators": [ "Colon and Rectal Surgery Inc.", "The Cleveland Clinic", "John Muir Health", "Oregon Health and Science University", "St. Joseph Hospital of Orange", "University of California, Irvine", "University of California, San Francisco", "University of Chicago", "University of South Florida", "University of Vermont", "University of Washington", "Medstar Health Research Institute", "Washington University School of Medicine", "Creighton University Medical Center", "The Methodist Hospital Research Institute", "University of Rochester", "University of Virginia", "St. Paul's Hospital", "St. Joseph, Florida", "Cleveland Clinic Florida", "University of Colorado, Denver", "University of Michigan" ], "collabIds": [], "outside": [ "Colon and Rectal Surgery Inc.", "The Cleveland Clinic", "John Muir Health", "Oregon Health and Science University", "St. Joseph Hospital of Orange", "University of California, Irvine", "University of California, San Francisco", "University of Chicago", "University of South Florida", "University of Vermont", "University of Washington", "Medstar Health Research Institute", "Washington University School of Medicine", "Creighton University Medical Center", "The Methodist Hospital Research Institute", "University of Rochester", "University of Virginia", "St. Paul's Hospital", "St. Joseph, Florida", "Cleveland Clinic Florida", "University of Colorado, Denver", "University of Michigan" ] }, { "unit": "U-APHINITY", "label": "APHINITY · adjuvant pertuzumab added to trastuzumab and chemotherapy", "lead": "Hoffmann-La Roche", "leadIds": [ "roche" ], "collaborators": [ "Genentech, Inc.", "Breast International Group" ], "collabIds": [ "roche" ], "outside": [ "Breast International Group" ] }, { "unit": "U-PALOMA3", "label": "PALOMA-3 · palbociclib plus fulvestrant after endocrine therapy", "lead": "Pfizer", "leadIds": [ "pfizer" ], "collaborators": [ "AstraZeneca" ], "collabIds": [ "astrazeneca" ], "outside": [] }, { "unit": "U-KN756", "label": "KEYNOTE-756 · neoadjuvant pembrolizumab in ER-positive early breast cancer", "lead": "Merck Sharp & Dohme LLC", "leadIds": [ "msd" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-KRISTINE", "label": "KRISTINE · neoadjuvant T-DM1 plus pertuzumab without conventional chemotherapy", "lead": "Hoffmann-La Roche", "leadIds": [ "roche" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-MONARCH2", "label": "MONARCH 2 · abemaciclib plus fulvestrant after endocrine therapy", "lead": "Eli Lilly and Company", "leadIds": [ "lilly" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-ML7", "label": "MONALEESA-7 · ribociclib plus endocrine therapy before menopause", "lead": "Novartis Pharmaceuticals", "leadIds": [ "novartis" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-PATINA", "label": "PATINA · palbociclib added to maintenance HER2 and endocrine therapy", "lead": "Alliance Foundation Trials, LLC.", "leadIds": [], "collaborators": [ "Pfizer", "GBG Forschungs GmbH", "Fondazione Michelangelo", "PrECOG, LLC.", "Breast Cancer Trials, Australia and New Zealand", "Syneos Health", "SOLTI Breast Cancer Research Group", "UNICANCER" ], "collabIds": [ "pfizer" ], "outside": [ "GBG Forschungs GmbH", "Fondazione Michelangelo", "PrECOG, LLC.", "Breast Cancer Trials, Australia and New Zealand", "Syneos Health", "SOLTI Breast Cancer Research Group", "UNICANCER" ] }, { "unit": "U-T-ARROW", "label": "ARROW (pralsetinib, RET-altered thyroid cohorts)", "lead": "Hoffmann-La Roche", "leadIds": [ "roche" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-IM050", "label": "IMpassion050: primary response and final follow-up", "lead": "Hoffmann-La Roche", "leadIds": [ "roche" ], "collaborators": [ "Chugai Pharmaceutical" ], "collabIds": [], "outside": [ "Chugai Pharmaceutical" ] }, { "unit": "U-BREAKWATER", "label": "BREAKWATER · first-line encorafenib, cetuximab and mFOLFOX6 in BRAF V600E colorectal cancer", "lead": "Pfizer", "leadIds": [ "pfizer" ], "collaborators": [ "Ono Pharmaceutical Co., Ltd.", "Merck KGaA, Darmstadt, Germany", "Eli Lilly and Company" ], "collabIds": [ "lilly" ], "outside": [ "Ono Pharmaceutical Co., Ltd.", "Merck KGaA, Darmstadt, Germany" ] }, { "unit": "U-ATOMIC", "label": "ATOMIC · adjuvant atezolizumab with FOLFOX in stage III dMMR colon cancer", "lead": "National Cancer Institute (NCI)", "leadIds": [ "nci-us" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-ML3", "label": "MONALEESA-3 · ribociclib plus fulvestrant", "lead": "Novartis Pharmaceuticals", "leadIds": [ "novartis" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-PALOMA2", "label": "PALOMA-2 · first-line palbociclib plus letrozole", "lead": "Pfizer", "leadIds": [ "pfizer" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-HER2CLIMB02", "label": "HER2CLIMB-02 · tucatinib added to T-DM1", "lead": "Seagen, a wholly owned subsidiary of Pfizer", "leadIds": [ "pfizer" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-T-ESTIMABL2", "label": "ESTIMABL2 · thyroidectomy with or without radioiodine in low-risk thyroid cancer", "lead": "Gustave Roussy, Cancer Campus, Grand Paris", "leadIds": [ "gustave-roussy" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-T-ESTIMABL1", "label": "ESTIMABL1 · radioiodine dose and stimulation method in low-risk thyroid cancer", "lead": "Gustave Roussy, Cancer Campus, Grand Paris", "leadIds": [ "gustave-roussy" ], "collaborators": [ "National Cancer Institute, France" ], "collabIds": [], "outside": [ "National Cancer Institute, France" ] }, { "unit": "U-T-ASTRA", "label": "ASTRA · selumetinib added to adjuvant radioactive iodine in high-risk differentiated thyroid cancer", "lead": "AstraZeneca", "leadIds": [ "astrazeneca" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-Ganetespib26", "label": "Fulvestrant with ganetespib in endocrine resistance: negative randomized phase II result", "lead": "Dana-Farber Cancer Institute", "leadIds": [ "dfci" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-PaxalisibBrain26", "label": "Paxalisib plus trastuzumab: no confirmed CNS responses at the recommended dose", "lead": "Dana-Farber Cancer Institute", "leadIds": [ "dfci" ], "collaborators": [ "Kazia Therapeutics Limited" ], "collabIds": [], "outside": [ "Kazia Therapeutics Limited" ] }, { "unit": "U-HypoMastIMNI26", "label": "HypoMast-IMNI: locoregional noninferiority and reduced acute skin toxicity", "lead": "Fudan University", "leadIds": [ "fuscc" ], "collaborators": [], "collabIds": [], "outside": [] }, { "unit": "U-LEAP017", "label": "LEAP-017 · lenvatinib plus pembrolizumab in previously treated pMMR colorectal cancer", "lead": "Merck Sharp & Dohme LLC", "leadIds": [ "msd" ], "collaborators": [ "Eisai Inc." ], "collabIds": [], "outside": [ "Eisai Inc." ] }, { "unit": "U-DCRC02", "label": "DESTINY-CRC02 · two doses of trastuzumab deruxtecan in HER2-positive colorectal cancer", "lead": "Daiichi Sankyo", "leadIds": [ "daiichi" ], "collaborators": [ "AstraZeneca" ], "collabIds": [ "astrazeneca" ], "outside": [] }, { "unit": "U-T-LENVA211", "label": "Study 211 · lenvatinib starting dose 18 mg versus 24 mg in radioiodine-refractory thyroid cancer", "lead": "Eisai Inc.", "leadIds": [], "collaborators": [ "Merck Sharp & Dohme LLC" ], "collabIds": [ "msd" ], "outside": [] }, { "unit": "U-INTEGRAL26", "label": "INTEGRAL: early termination of intratumoral IL-12 combination in anthracycline-refractory TNBC", "lead": "The Methodist Hospital Research Institute", "leadIds": [], "collaborators": [ "Merck Sharp & Dohme LLC" ], "collabIds": [ "msd" ], "outside": [] }, { "unit": "U-CALGB80405", "label": "CALGB/SWOG 80405 · cetuximab or bevacizumab with first-line chemotherapy", "lead": "Alliance for Clinical Trials in Oncology", "leadIds": [], "collaborators": [ "National Cancer Institute (NCI)", "SWOG Cancer Research Network", "Bristol-Myers Squibb", "Aptuit" ], "collabIds": [ "nci-us" ], "outside": [ "SWOG Cancer Research Network", "Bristol-Myers Squibb", "Aptuit" ] } ], "dossiers": [ { "id": "SD-ERBB2", "target": "ERBB2", "uniprot": "P04626", "alphafold": [ "AF-P04626-F1" ], "experimental": [ { "id": "1N8Z", "title": "Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab", "method": "X-RAY DIFFRACTION", "resolution": 2.52, "released": "2003-02-18", "deposited": "2002-11-21", "citation": { "title": "Structure of the Extracellular Region of HER2 Alone and in Complex with the Herceptin Fab", "journal": "Nature", "year": 2003, "pmid": "12610629", "doi": "10.1038/nature01392" }, "url": "https://www.rcsb.org/structure/1N8Z", "kind": "Experimental structure" }, { "id": "1S78", "title": "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex", "method": "X-RAY DIFFRACTION", "resolution": 3.25, "released": "2004-04-27", "deposited": "2004-01-29", "citation": { "title": "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.", "journal": "Cancer Cell", "year": 2004, "pmid": "15093539", "doi": "10.1016/S1535-6108(04)00083-2" }, "url": "https://www.rcsb.org/structure/1S78", "kind": "Experimental structure" }, { "id": "3PP0", "title": "Crystal Structure of the Kinase domain of Human HER2 (erbB2).", "method": "X-RAY DIFFRACTION", "resolution": 2.25, "released": "2011-03-30", "deposited": "2010-11-23", "citation": { "title": "Structural Analysis of the Mechanism of Inhibition and Allosteric Activation of the Kinase Domain of HER2 Protein.", "journal": "J Biol Chem", "year": 2011, "pmid": "21454582", "doi": "10.1074/jbc.M110.206193" }, "url": "https://www.rcsb.org/structure/3PP0", "kind": "Experimental structure" }, { "id": "3RCD", "title": "HER2 Kinase Domain Complexed with TAK-285", "method": "X-RAY DIFFRACTION", "resolution": 3.21, "released": "2011-11-23", "deposited": "2011-03-30", "citation": { "title": "Design and Synthesis of Novel Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors Bearing a Pyrrolo[3,2-d]pyrimidine Scaffold.", "journal": "J Med Chem", "year": 2011, "pmid": "22003817", "doi": "10.1021/jm2008634" }, "url": "https://www.rcsb.org/structure/3RCD", "kind": "Experimental structure" } ], "context": { "gastric": "HER2-positive gastric cancer; HER2 status can be lost after trastuzumab (see QP-06).", "breast": "HER2-positive and HER2-low breast cancer." }, "comparison": "The AlphaFold entry is a full-length monomer with no antibody, no membrane, no glycans and no partner receptor. The experimental entries cover single domains or the extracellular region in complex with antibody fragments: 1N8Z (trastuzumab Fab), 1S78 (pertuzumab Fab), 3PP0 and 3RCD (kinase domain, the latter with an inhibitor).", "observations": [ "Trastuzumab and pertuzumab bind different regions of the extracellular domain: the juxtamembrane region and the centre of domain II (primary citations of 1N8Z and 1S78).", "The very-low-confidence fraction of the AlphaFold model marks residues whose placement should not be read." ], "questions": [ "Do the antibody epitopes differ between the gastric-specific and breast HER2 scoring contexts? (a pathology question, not answerable from structure)", "Which regions change conformation on dimerisation? Needs complexes, not the monomer model." ], "notFromStructure": [ "Whether an antibody will work in gastric vs breast cancer.", "Why pertuzumab failed in gastric cancer while it succeeded in breast cancer (QP-01)." ], "needs": [ "Receptor-dimer complexes", "Mapping of scoring-relevant epitopes to IHC antibodies" ], "pairs": [ "QP-01", "QP-06" ], "predicted": [ { "entryId": "AF-P04626-F1", "accession": "P04626", "version": 6, "created": "2025-08-01", "mean": 74, "veryHigh": 0.422, "confident": 0.246, "low": 0.086, "veryLow": 0.245, "span": [ 1, 1255 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P04626-F1", "kind": "Predicted model" } ], "experimentalTotal": 63, "searches": null, "analysis": null }, { "id": "SD-CLDN18", "target": "CLDN18.2", "uniprot": "P56856", "alphafold": [ "AF-P56856-F1", "AF-P56856-2-F1" ], "experimental": [ { "id": "9V32", "title": "Human claudin 18.2 in complex with the Fab fragment of Zolbetuximab", "method": "ELECTRON MICROSCOPY", "resolution": 4.1, "released": "2026-05-27", "deposited": "2025-05-21", "citation": { "title": "Recognition of human claudin 18.2 by therapeutic antibodies", "journal": "To be published", "year": null, "pmid": null, "doi": null }, "url": "https://www.rcsb.org/structure/9V32", "kind": "Experimental structure" }, { "id": "9V2U", "title": "Human claudin 18.2 in complex with the Fab fragment of Osemitamab (TST001)", "method": "ELECTRON MICROSCOPY", "resolution": 3.8, "released": "2026-05-27", "deposited": "2025-05-20", "citation": { "title": "Recognition of human claudin 18.2 by therapeutic antibodies", "journal": "To be published", "year": null, "pmid": null, "doi": null }, "url": "https://www.rcsb.org/structure/9V2U", "kind": "Experimental structure" }, { "id": "9V31", "title": "Human claudin 18.2 (dimer form) in complex with the Fab fragment of Osemitamab (TST001)", "method": "ELECTRON MICROSCOPY", "resolution": 4.4, "released": "2026-05-27", "deposited": "2025-05-21", "citation": { "title": "Recognition of human claudin 18.2 by therapeutic antibodies", "journal": "To be published", "year": null, "pmid": null, "doi": null }, "url": "https://www.rcsb.org/structure/9V31", "kind": "Experimental structure" } ], "context": { "gastric": "CLDN18.2-positive gastric cancer selected by IHC; thresholds differ by study (QP-07).", "breast": "Not studied here." }, "comparison": "The default AlphaFold entry (AF-P56856-F1) is isoform A1. CLDN18.2 is isoform A2 and has its own entry (AF-P56856-2-F1). Analysis A3 shows the two isoforms differ only within residues 1–69. The cryo-EM entries (released 2026) show CLDN18.2 with the Fab of zolbetuximab (9V32) or osemitamab (9V2U, 9V31).", "observations": [ "Isoform-specific residues fall in the N-terminal cytoplasmic segment, the first transmembrane helix and most of the first extracellular segment (A3).", "The experimental entries have no primary citation in the PDB as of 2026-09-28." ], "questions": [ "Do the zolbetuximab contact residues in 9V32 lie inside residues 1–69, the isoform-specific stretch?" ], "notFromStructure": [ "Whether the IHC thresholds select the same patients (QP-07).", "Clinical activity of either antibody." ], "needs": [ "Contact-residue map from 9V32", "Primary publication for the cryo-EM entries" ], "pairs": [ "QP-07", "QP-13" ], "predicted": [ { "entryId": "AF-P56856-F1", "accession": "P56856", "version": 6, "created": "2025-08-01", "mean": 72.81, "veryHigh": 0.314, "confident": 0.28, "low": 0.199, "veryLow": 0.207, "span": [ 1, 261 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P56856-F1", "kind": "Predicted model" }, { "entryId": "AF-P56856-2-F1", "accession": "P56856-2", "version": 6, "created": "2025-08-01", "mean": 73.12, "veryHigh": 0.318, "confident": 0.276, "low": 0.199, "veryLow": 0.207, "span": [ 1, 261 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P56856-2-F1", "kind": "Predicted model" } ], "experimentalTotal": 3, "searches": null, "analysis": { "id": "A3", "title": "CLDN18 isoform A1 (canonical) vs isoform A2 (CLDN18.2) sequence comparison", "retrieved": "2026-09-28", "method": "UniProt REST FASTA for both isoform accessions, position-by-position comparison; topology and alternative-sequence annotation read from the P56856 entry. The topology is annotated for the canonical isoform; whether it holds for A2 is not shown here.", "lengths": { "P56856-1": 261, "P56856-2": 261 }, "differingPositions": 21, "span": { "first": 2, "last": 69 }, "identicalFrom": 70, "differences": [ { "pos": 2, "a1": "S", "a2": "A" }, { "pos": 3, "a1": "T", "a2": "V" }, { "pos": 5, "a1": "T", "a2": "A" }, { "pos": 8, "a1": "V", "a2": "G" }, { "pos": 9, "a1": "V", "a2": "L" }, { "pos": 10, "a1": "A", "a2": "G" }, { "pos": 12, "a1": "L", "a2": "V" }, { "pos": 13, "a1": "L", "a2": "V" }, { "pos": 15, "a1": "I", "a2": "L" }, { "pos": 16, "a1": "L", "a2": "I" }, { "pos": 18, "a1": "L", "a2": "I" }, { "pos": 21, "a1": "C", "a2": "I" }, { "pos": 26, "a1": "G", "a2": "C" }, { "pos": 29, "a1": "M", "a2": "Q" }, { "pos": 37, "a1": "D", "a2": "N" }, { "pos": 42, "a1": "S", "a2": "A" }, { "pos": 45, "a1": "Q", "a2": "N" }, { "pos": 47, "a1": "E", "a2": "Q" }, { "pos": 56, "a1": "Q", "a2": "E" }, { "pos": 65, "a1": "P", "a2": "G" }, { "pos": 69, "a1": "I", "a2": "L" } ], "topology": [ { "type": "Topological domain", "start": 1, "end": 6, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 7, "end": 27, "description": "Helical" }, { "type": "Topological domain", "start": 28, "end": 80, "description": "Extracellular" }, { "type": "Transmembrane", "start": 81, "end": 101, "description": "Helical" }, { "type": "Topological domain", "start": 102, "end": 122, "description": "Cytoplasmic" }, { "type": "Transmembrane", "start": 123, "end": 143, "description": "Helical" }, { "type": "Topological domain", "start": 144, "end": 174, "description": "Extracellular" }, { "type": "Transmembrane", "start": 175, "end": 195, "description": "Helical" }, { "type": "Topological domain", "start": 196, "end": 261, "description": "Cytoplasmic" } ], "alternativeSequence": [ { "start": 1, "end": 69, "description": "in isoform A2" } ], "regionsTouched": [ "Topological domain 1-6 (Cytoplasmic)", "Transmembrane 7-27 (Helical)", "Topological domain 28-80 (Extracellular)" ] } }, { "id": "SD-ESR1", "target": "ESR1", "uniprot": "P03372", "alphafold": [ "AF-P03372-F1" ], "experimental": [ { "id": "1ERE", "title": "HUMAN ESTROGEN RECEPTOR LIGAND-BINDING DOMAIN IN COMPLEX WITH 17BETA-ESTRADIOL", "method": "X-RAY DIFFRACTION", "resolution": 3.1, "released": "1998-09-16", "deposited": "1997-09-08", "citation": { "title": "Molecular basis of agonism and antagonism in the oestrogen receptor.", "journal": "Nature", "year": 1997, "pmid": "9338790", "doi": "10.1038/39645" }, "url": "https://www.rcsb.org/structure/1ERE", "kind": "Experimental structure" }, { "id": "3ERT", "title": "HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 4-HYDROXYTAMOXIFEN", "method": "X-RAY DIFFRACTION", "resolution": 1.9, "released": "1999-04-08", "deposited": "1999-03-30", "citation": { "title": "The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.", "journal": "Cell", "year": 1998, "pmid": "9875847", "doi": "10.1016/S0092-8674(00)81717-1" }, "url": "https://www.rcsb.org/structure/3ERT", "kind": "Experimental structure" } ], "context": { "breast": "HR-positive breast cancer; ESR1 mutations enrich after endocrine therapy (A2).", "gastric": "Not studied here." }, "comparison": "The AlphaFold entry is one static, ligand-free model of the full receptor. The experimental ligand-binding-domain structures differ by ligand: agonist (1ERE, oestradiol) and antagonist (3ERT, 4-hydroxytamoxifen). Many further entries carry the Y537S mutation (count saved in structures.json).", "observations": [ "Agonist and antagonist ligands induce different conformations of the transactivation region (primary citation of 1ERE).", "Y537S and D538G are reported to stabilise the AF-2-binding conformation (Fanning 2016) — a state change a single static model cannot show." ], "questions": [ "How does the ligand-binding-domain conformation differ between wild-type and Y537S entries bound to the same ligand class?" ], "notFromStructure": [ "Whether switching therapy at ESR1 emergence prolongs survival (QP-08)." ], "needs": [ "Matched wild-type/mutant pairs with the same ligand", "Dynamics or ensemble data" ], "pairs": [ "QP-02", "QP-08" ], "predicted": [ { "entryId": "AF-P03372-F1", "accession": "P03372", "version": 6, "created": "2025-08-01", "mean": 66.44, "veryHigh": 0.435, "confident": 0.069, "low": 0.032, "veryLow": 0.464, "span": [ 1, 595 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P03372-F1", "kind": "Predicted model" } ], "experimentalTotal": 493, "searches": { "total": 131, "ids": [ "9WB2", "9VT5", "9VTU", "9W11", "9W12", "9W13", "9BPX", "9BQE", "9BU1", "7YMK", "7Y8F", "7Y8G" ] }, "analysis": null }, { "id": "SD-PIK3CA", "target": "PIK3CA", "uniprot": "P42336", "alphafold": [ "AF-P42336-F1" ], "experimental": [ { "id": "4JPS", "title": "Co-crystal Structures of the Lipid Kinase PI3K alpha with Pan and Isoform Selective Inhibitors", "method": "X-RAY DIFFRACTION", "resolution": 2.2, "released": "2014-04-02", "deposited": "2013-03-19", "citation": { "title": "Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation.", "journal": "Bioorg Med Chem Lett", "year": 2013, "pmid": "23726034", "doi": "10.1016/j.bmcl.2013.05.007" }, "url": "https://www.rcsb.org/structure/4JPS", "kind": "Experimental structure" } ], "context": { "breast": "PIK3CA-mutated HR-positive breast cancer.", "gastric": "Recurrent PIK3CA mutation in the EBV-positive TCGA subtype; no trial in the library." }, "comparison": "The AlphaFold entry models the p110α catalytic subunit alone. 4JPS contains both p110α and the p85α regulatory subunit with an inhibitor bound. A high model confidence therefore describes the isolated chain, not the heterodimer that functions in cells.", "observations": [ "4JPS has two polymer entities: the catalytic subunit alpha and the regulatory subunit alpha (RCSB, 2026-09-28).", "The RLY-2608 paper used molecular dynamics and cryo-EM to describe an allosteric network in mutant PI3Kα." ], "questions": [ "Where do hotspot mutations sit relative to the p85α interface in 4JPS?" ], "notFromStructure": [ "Clinical toxicity differences between orthosteric and mutant-selective inhibitors." ], "needs": [ "Mutant heterodimer structures", "Clinical data from the registered phase 3 (NCT06982521)" ], "pairs": [ "QP-02" ], "predicted": [ { "entryId": "AF-P42336-F1", "accession": "P42336", "version": 6, "created": "2025-08-01", "mean": 92.38, "veryHigh": 0.822, "confident": 0.117, "low": 0.05, "veryLow": 0.011, "span": [ 1, 1068 ], "page": "https://alphafold.ebi.ac.uk/entry/AF-P42336-F1", "kind": "Predicted model" } ], "experimentalTotal": 139, "searches": null, "analysis": null } ], "roles": [ { "id": "AG-LEAD", "name": "Research Lead", "state": "partial", "remit": "Set priorities, name the standing hypotheses, and record why work is running, held or stopped — so that the decision, not just the result, is reviewable.", "ran": [ "Wrote the 14 question–judgment pairs, each with the condition that would change the judgment.", "Marked two questions as held rather than answered (QP-08 waiting on survival data, QP-11 waiting on a randomised comparison)." ], "didNot": [ "No resource plan, so \"priority\" here means order of interest, not a funded queue." ], "outputs": [ "QP-01…QP-14" ] }, { "id": "AG-G", "name": "Gastric Cancer Lead", "state": "partial", "remit": "Hold the clinical and biological context of gastric cancer and judge which target evidence is solid enough to build on.", "ran": [ "Curated 32 gastric evidence units including the four HER2 agents that failed.", "Recorded that HER2 scoring and CLDN18.2 thresholds are study-specific, not universal." ], "didNot": [ "Did not read the full PDQ section on stages 0–III; only the advanced-disease options were extracted.", "Did not cover peritoneal metastasis as its own literature." ], "outputs": [ "U-ToGA…U-TCGASTAD", "QP-06", "QP-07" ] }, { "id": "AG-B", "name": "Breast Cancer Lead", "state": "partial", "remit": "Hold subtype-specific context: HER2 level, endocrine resistance, recurrence and response differences.", "ran": [ "Curated 36 breast evidence units across the three subtypes plus the HER2-level axis.", "Built the HR status × HER2 level matrix and left the empty cells visible." ], "didNot": [ "Did not curate adjuvant HER2 trials, or brain-metastasis-specific evidence." ], "outputs": [ "U-CLEOPATRA…U-OlympiA", "QP-08", "QP-10" ] }, { "id": "AG-STRUCT", "name": "Structural Biology Analyst", "state": "partial", "remit": "Compare predicted and experimental structures and write down where structural reading stops.", "ran": [ "Four structure dossiers with the experimental/predicted difference stated for each.", "Ran A3, which found the isoform difference that makes the default CLDN18 model the wrong one to use.", "Read and recorded the published limits of the prediction model and its terms of use." ], "didNot": [ "Did not open a single structure file. No contact-residue analysis, no superposition, no per-residue confidence read beyond the summary values the API returns." ], "outputs": [ "SD-ERBB2", "SD-CLDN18", "SD-ESR1", "SD-PIK3CA", "A3" ] }, { "id": "AG-TRANS", "name": "Translational Research Analyst", "state": "designed", "remit": "Say what a structural or cell-level observation still needs before it can be called a disease-level finding.", "ran": [], "didNot": [ "Nothing ran. The \"not from structure\" lines in the dossiers are the placeholder for this role and were written by the same session, not checked by a second one." ], "outputs": [] }, { "id": "AG-DATA", "name": "Data & Statistics Analyst", "state": "partial", "remit": "Run the open-data analyses and state comparison groups, confounders, uncertainty and reproducibility.", "ran": [ "A1, A2 and A3 executed from scripts that re-run end to end.", "Denominators printed with every percentage; group definitions taken from the study's own recorded fields." ], "didNot": [ "No statistical test, no confidence interval, no adjustment. The analyses are counts, and the library says so. A2 compares samples from different patients, which is stated as a limit rather than modelled." ], "outputs": [ "A1", "A2", "A3" ] }, { "id": "AG-CURATE", "name": "Evidence Curator", "state": "executed", "remit": "Keep every source identifier, date, and correction status, and prevent one study from being counted twice.", "ran": [ "All 83 papers, 53 trials, 13 proteins and 20 structures re-fetched from their APIs, with the retrieval date stored.", "Retraction and expression-of-concern check: none found.", "Seven papers carry errata; the notices were fetched, have no abstracts, and are marked unreviewed with links.", "Duplicate-identifier check: none. Every internal reference resolves (0 problems).", "Four trials are reported by more than one paper and are listed so they stay one evidence unit." ], "didNot": [ "Did not open the journal pages of the errata, so whether a correction touches a cited number is unknown." ], "outputs": [ "data/sources/*", "data/sources/integrity.json" ] }, { "id": "AG-CRIT", "name": "Critical Reviewer", "state": "partial", "remit": "Find the counter-evidence, the alternative explanation, the over-reach, and the condition that would reject the hypothesis.", "ran": [ "Every pair carries an objection and a stated condition that would change the judgment.", "Negative and mixed trials were curated deliberately, not only positive ones: 8 negative and 4 mixed units, plus 3 registry records left explicitly uncurated.", "Rejected one framing during the work: a claim that structure confidence ranks targets (QP-02)." ], "didNot": [ "Did not search systematically for contradicting studies; the negative evidence here is the negative evidence of trials already known to the session. A systematic search is not done." ], "outputs": [ "objection and changesMind fields of QP-01…QP-14" ] }, { "id": "AG-COORD", "name": "Research Coordinator", "state": "partial", "remit": "Track inputs, dependencies, next checks and deliverables.", "ran": [ "Every pair ends with concrete next steps; every dataset carries a connection status; every feature carries a build state." ], "didNot": [ "No owner, no date and no effort estimate on any next step beyond the five gap actions." ], "outputs": [ "next fields", "dataset status", "feature status" ] } ], "disclosure": { "reality": "The initial draft was produced in one model session on 2026-09-28. Later library updates and computational reproductions used separately tasked Codex agents; provenance is recorded per output. This is internal AI-assisted work, not independent external peer review. The roles below retain the initial draft checklist.", "doubleCounting": "Several papers report the same trial. The library counts one evidence unit per trial, and the integrity check lists which trials have more than one paper so the count cannot drift.", "disagreement": "No formal blinded disagreement assessment between the nine proposed roles has been conducted. Where the evidence itself conflicts, both sides are kept in the unit and in the pair (objection field)." }, "benchmark": { "method": { "built": "2026-09-28", "standing": "This is a comparison set assembled by IATHEON, not an official or global ranking. No recognised world ranking exists for the areas below.", "selection": [ "Ran a phase 3 trial or published a paper that this library already cites as evidence, or", "Runs a public resource that this draft queries (structures, predictions, sequences, genomics), or", "Is a national or comprehensive cancer centre in a country where gastric cancer incidence is high, and publishes on it." ], "excluded": "Institutions whose relevant work exists but is registered or published only in sources this draft does not query are under-counted; that is stated on every affected row rather than corrected silently.", "weights": "None. Areas are ranked separately and never summed into one score, because the indicators measure different things and an institution type can be strong in one area by definition.", "missing": "A missing or zero value is reported as \"not measured\" with the query that produced it. It is never imputed and never treated as a low score.", "unit": "One row is one organisation counted the same way for every institution (2026-11-06). A university-based centre is counted as its university medical system: the medical school with its own and teaching hospitals (for example Seoul National University with SNUH, Bundang and Boramae; Yonsei with the Severance hospitals; Sungkyunkwan University with the Samsung hospitals). An independent cancer centre without a parent university medical system of its own is counted as the centre. Companies are counted with their named subsidiaries. Every row shows its exact PubMed and ClinicalTrials.gov expression in its institution profile.", "overlap": "A paper with authors from two institutions is counted once for each of them, so columns overlap and do not add up to a total.", "rounding": "Counts are integers as returned by the API on the retrieval date. Re-running the scripts on a later date will give different numbers; the date is printed beside every count." }, "note": "Comparison set constructed by IATHEON on 2026-09-28; institution units made consistent on 2026-11-06 (founder decision, \"합리적 잣대로 순위를 다시 매겨\"). Not an official or global ranking. ctgov = ClinicalTrials.gov sponsor/collaborator expression (null = not a clinical-trial sponsor by role). pubmed = PubMed affiliation expression. Types: center, industry, infrastructure. unit = what one row counts. pubmedNarrow/ctgovNarrow = the earlier hospital-name-only expression, kept for the sensitivity line.", "checked": "2026-11-06", "sources": { "trials": "ClinicalTrials.gov API v2 (query.spons = sponsor or collaborator; query.lead = lead sponsor)", "pubs": "NCBI PubMed E-utilities esearch (count only)" }, "windows": { "trials": "start date 2016-01-01 to 2025-12-31, interventional", "completedLead": "start 2016-01-01 to 2023-12-31, status completed, lead sponsor", "pubs": "2021-2025 publication date" }, "conditions": { "gastric": "(gastric cancer OR stomach cancer OR gastroesophageal junction adenocarcinoma)", "breast": "breast cancer" }, "topics": { "gastric": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab])", "breast": "(breast neoplasms[mh] OR breast cancer[tiab])", "structuralAny": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab])", "structural": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh])" }, "resultsFilterWorks": true, "institutions": [ { "id": "ncc-korea", "name": "National Cancer Center, Korea", "country": "KR", "type": "center", "ctgov": "\"National Cancer Center, Korea\"", "pubmed": "\"National Cancer Center\"[ad] AND (Korea[ad] OR Goyang[ad])", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "National cancer centre in the same country and health system as RISCON Labs; gastric cancer is a high-incidence disease there.", "learn": "Screening-era cohorts and prevention trials that a Korean research programme can realistically join.", "collab": "Possible route to Korean cohort data; nothing approached." }, "indicators": { "id": "ncc-korea", "trials": { "gastric": { "n": 17, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Korea%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Korea%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Korea%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Korea%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Korea%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Center%2C+Korea%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Center%2C+Korea%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 265, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"National Cancer Center\"[ad] AND (Korea[ad] OR Goyang[ad]) AND 2021:2025[dp]" }, "breast": { "n": 320, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"National Cancer Center\"[ad] AND (Korea[ad] OR Goyang[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 12, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"National Cancer Center\"[ad] AND (Korea[ad] OR Goyang[ad]) AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"National Cancer Center\"[ad] AND (Korea[ad] OR Goyang[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 1, "completed": 9, "pct": 11.1 }, "representative": [ { "nct": "NCT06780748", "title": "Photo-medicine-Guided Dual Approach for Reoperation of Sentinel Lymph Nodes in Locally Recurrent Breast Cancer Patients", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2023-08-13", "conditions": [ "Breast Cancer", "Locally Recurrent Breast Cancer", "Sentinel Lymph Node Biopsy (SLNB)" ] }, { "nct": "NCT05750290", "title": "CKD-702 Plus Irinotecan in Gastric Cancer", "acronym": null, "phases": [ "PHASE2" ], "status": "UNKNOWN", "start": "2022-12-01", "conditions": [ "Gastric Cancer" ] }, { "nct": "NCT04214990", "title": "Aspirin Use for Gastric Cancer Prevention in the Early Gastric Cancer Patients", "acronym": "EASTERN", "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2020-02-15", "conditions": [ "Aspirin", "Gastric Cancer" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "smc", "name": "Sungkyunkwan University (Samsung Medical Center, Kangbuk Samsung, Samsung Changwon)", "country": "KR", "type": "center", "ctgov": "\"Samsung Medical Center\" OR \"Sungkyunkwan University\" OR \"Kangbuk Samsung Hospital\" OR \"Samsung Changwon Hospital\"", "pubmed": "(\"Sungkyunkwan University\"[ad] OR \"Samsung Medical Center\"[ad] OR \"Kangbuk Samsung\"[ad] OR \"Samsung Changwon\"[ad])", "pubmedNarrow": "\"Samsung Medical Center\"[ad]", "ctgovNarrow": "\"Samsung Medical Center\"", "unit": "University medical system: Sungkyunkwan University School of Medicine and its Samsung teaching hospitals.", "note": { "why": "Ran the umbrella screening protocol that reported how often molecular screening reached a matched treatment.", "learn": "How to link a sequencing pipeline to parallel trial arms and report the fraction that actually reaches assignment.", "collab": "The screening design is published; the data are not open." }, "indicators": { "id": "smc", "trials": { "gastric": { "n": 24, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 29, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 143, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 5, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Samsung+Medical+Center%22+OR+%22Sungkyunkwan+University%22+OR+%22Kangbuk+Samsung+Hospital%22+OR+%22Samsung+Changwon+Hospital%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 317, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Sungkyunkwan University\"[ad] OR \"Samsung Medical Center\"[ad] OR \"Kangbuk Samsung\"[ad] OR \"Samsung Changwon\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 713, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Sungkyunkwan University\"[ad] OR \"Samsung Medical Center\"[ad] OR \"Kangbuk Samsung\"[ad] OR \"Samsung Changwon\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 97, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"Sungkyunkwan University\"[ad] OR \"Samsung Medical Center\"[ad] OR \"Kangbuk Samsung\"[ad] OR \"Samsung Changwon\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 3, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"Sungkyunkwan University\"[ad] OR \"Samsung Medical Center\"[ad] OR \"Kangbuk Samsung\"[ad] OR \"Samsung Changwon\"[ad]) AND 2021:2025[dp]" } }, "pubsNarrow": { "gastric": { "n": 246, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Samsung Medical Center\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 532, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Samsung Medical Center\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 5, "completed": 143, "pct": 3.5 }, "representative": [ { "nct": "NCT07757958", "title": "Partial Breast Irradiation Without Sentinel Lymph Node Biopsy in Low-Risk Early Breast Cancer", "acronym": "APROOB", "phases": [ "PHASE3" ], "status": "NOT_YET_RECRUITING", "start": "2026-08-01", "conditions": [ "Breast Cancer", "Node-negative Breast Cancer", "Early-Stage Invasive Breast Carcinoma" ] }, { "nct": "NCT04656002", "title": "As a Second-line Treatment for Metastatic Gastric Adenocarcinoma Patients, the Safety and Effective of Vactosertib Administration in Combination With Paclitaxel+Ramucirumab is Evaluated, and a Phase 2a Clinical Trial to Biomarkers", "acronym": null, "phases": [ "PHASE2" ], "status": "UNKNOWN", "start": "2022-10", "conditions": [ "Gastric Cancer" ] }, { "nct": "NCT04819243", "title": "PALbociclib Endocrine Therapy Followed by Talazo Vs. Talazoz-Atezo Study", "acronym": "Young-PALETTA", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2021-08-25", "conditions": [ "Premenopausal HR+/HER2- Metastatic Breast Cancer" ] } ], "evidence": { "total": 3, "lead": 3, "positive": 0, "negativeOrMixed": 2, "units": [ { "unit": "U-VIKTORY", "label": "VIKTORY", "role": "lead sponsor", "result": "descriptive", "program": "gastric", "phases": [ "NA" ] }, { "unit": "U-ARTIST2", "label": "ARTIST 2 · postoperative chemotherapy and radiation", "role": "lead sponsor", "result": "mixed", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-ARTIST", "label": "ARTIST · adjuvant chemotherapy with or without radiotherapy", "role": "lead sponsor", "result": "negative", "program": "gastric", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "yonsei", "name": "Yonsei University (Severance, Gangnam, Yongin)", "country": "KR", "type": "center", "ctgov": "\"Yonsei University\" OR \"Severance Hospital\"", "pubmed": "(\"Yonsei University\"[ad] OR \"Severance\"[ad])", "pubmedNarrow": "(\"Yonsei University\"[ad] OR \"Severance Hospital\"[ad])", "ctgovNarrow": "\"Yonsei University\"", "unit": "University medical system: Yonsei University College of Medicine and the Severance hospitals.", "note": { "why": "Second-largest gastric-cancer publication count among the Korean university medical systems in this set, with ongoing HER2-low and TROP2 studies.", "learn": "Sustained single-centre output on one cancer over years.", "collab": "None approached." }, "indicators": { "id": "yonsei", "trials": { "gastric": { "n": 49, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Yonsei+University%22+OR+%22Severance+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Yonsei+University%22+OR+%22Severance+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 32, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Yonsei+University%22+OR+%22Severance+Hospital%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Yonsei+University%22+OR+%22Severance+Hospital%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Yonsei+University%22+OR+%22Severance+Hospital%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 247, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Yonsei+University%22+OR+%22Severance+Hospital%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 4, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Yonsei+University%22+OR+%22Severance+Hospital%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 431, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Yonsei University\"[ad] OR \"Severance\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 727, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Yonsei University\"[ad] OR \"Severance\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 98, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"Yonsei University\"[ad] OR \"Severance\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 6, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"Yonsei University\"[ad] OR \"Severance\"[ad]) AND 2021:2025[dp]" } }, "pubsNarrow": { "gastric": { "n": 426, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Yonsei University\"[ad] OR \"Severance Hospital\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 723, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Yonsei University\"[ad] OR \"Severance Hospital\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 4, "completed": 247, "pct": 1.6 }, "representative": [ { "nct": "NCT07788222", "title": "Sacituzumab Govitecan and Q901 in Advanced TNBC", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-09-01", "conditions": [ "Triple Negative Breast Neoplasms" ] }, { "nct": "NCT05894824", "title": "T-Dxd in Combination With Ramucirumab as HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2024-02-05", "conditions": [ "Gastric Cancer", "Gastroesophageal Junction (GEJ) Cancer" ] }, { "nct": "NCT06677944", "title": "Preoperative Partial Breast Irradiation in Early-Stage Breast Cancer", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2023-10-13", "conditions": [ "Breast Cancer", "Ductal Carcinoma in Situ", "Invasive Breast Cancer" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "snuh", "name": "Seoul National University (SNUH, Bundang, Boramae)", "country": "KR", "type": "center", "ctgov": "\"Seoul National University\" OR \"Boramae Medical Center\"", "pubmed": "(\"Seoul National University\"[ad] OR \"Boramae\"[ad])", "pubmedNarrow": "\"Seoul National University Hospital\"[ad]", "ctgovNarrow": "\"Seoul National University Hospital\"", "unit": "University medical system: Seoul National University College of Medicine and its hospitals (SNUH, Bundang, SMG-SNU Boramae).", "note": { "why": "University medical system with the widest lead-sponsored trial portfolio among the Korean institutions in this set.", "learn": "Investigator-initiated trials on de-escalation questions industry does not fund.", "collab": "None approached." }, "indicators": { "id": "snuh", "trials": { "gastric": { "n": 24, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 31, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 4, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 419, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 15, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Seoul+National+University%22+OR+%22Boramae+Medical+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 523, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Seoul National University\"[ad] OR \"Boramae\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 907, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Seoul National University\"[ad] OR \"Boramae\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 253, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"Seoul National University\"[ad] OR \"Boramae\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 7, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"Seoul National University\"[ad] OR \"Boramae\"[ad]) AND 2021:2025[dp]" } }, "pubsNarrow": { "gastric": { "n": 238, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Seoul National University Hospital\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 450, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Seoul National University Hospital\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 15, "completed": 419, "pct": 3.6 }, "representative": [ { "nct": "NCT06704945", "title": "No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy", "acronym": "Neo-NAUTILUS", "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-06-04", "conditions": [ "Breast Cancer", "Neoadjuvant Therapy", "Sentinel Lymph Node Biopsy" ] }, { "nct": "NCT05536128", "title": "Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors After a CDK4/6 Inhibitor", "acronym": "Post-CDK", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2022-12-31", "conditions": [ "Advanced Breast Cancer" ] }, { "nct": "NCT05440149", "title": "The Postoperative Radiotherapy in N1 Breast Cancer Patients", "acronym": "PORT-N1", "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2022-08-01", "conditions": [ "Radiotherapy", "Breast Cancer" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "ncc-japan", "name": "National Cancer Center Japan", "country": "JP", "type": "center", "ctgov": "\"National Cancer Center, Japan\" OR \"National Cancer Center Hospital East\"", "pubmed": "\"National Cancer Center\"[ad] AND (Japan[ad] OR Tokyo[ad] OR Kashiwa[ad])", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "Highest gastric-cancer publication count among the independent cancer centres in the set; Japanese trials define much of the gastric evidence base.", "learn": "Gastric cancer as a primary programme rather than a secondary one.", "collab": "None approached.", "caveat": "Japanese trials registered only in jRCT are invisible to our ClinicalTrials.gov counts." }, "indicators": { "id": "ncc-japan", "trials": { "gastric": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Center%2C+Japan%22+OR+%22National+Cancer+Center+Hospital+East%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 609, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"National Cancer Center\"[ad] AND (Japan[ad] OR Tokyo[ad] OR Kashiwa[ad]) AND 2021:2025[dp]" }, "breast": { "n": 426, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"National Cancer Center\"[ad] AND (Japan[ad] OR Tokyo[ad] OR Kashiwa[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 6, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"National Cancer Center\"[ad] AND (Japan[ad] OR Tokyo[ad] OR Kashiwa[ad]) AND 2021:2025[dp]" }, "structural": { "n": 3, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"National Cancer Center\"[ad] AND (Japan[ad] OR Tokyo[ad] OR Kashiwa[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 2, "completed": 8, "pct": 25 }, "representative": [ { "nct": "NCT07699939", "title": "Perioperative HLX10 (Serplulimab) With S-1+Oxaliplatin (SOX) in Locally Advanced and PD-L1-Positive Gastric or Esophagogastric Junction Adenocarcinoma", "acronym": "PLATANUS", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2026-07-15", "conditions": [ "Gastric Adenocarcinoma", "Gastroesophageal Junction (GEJ) Adenocarcinoma" ] }, { "nct": "NCT07018570", "title": "An Open Label Phase 2 Study of Total Neoadjuvant Therapy (TNT) Consisting of FLOT With Pembrolizumab and Short Radiation for Patients With Locally Advanced Gastroesophageal Junction Adenocarcinoma", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-07-24", "conditions": [ "Gastroesophageal Junction (GEJ) Adenocarcinoma" ] }, { "nct": "NCT07529613", "title": "Trastuzumab Deruxtecan Plus Nivolumab Plus Capecitabine Plus Oxaliplatin for HER2 Low Gastric and Gastroesophageal Junction Adenocarcinoma", "acronym": "T-DXd_HER2Low", "phases": [ "PHASE1", "PHASE2" ], "status": "COMPLETED", "start": "2023-12-20", "conditions": [ "Gastric Adenocarcinoma", "Gastroesophageal Junction Adenocarcinoma" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "pkuch", "name": "Peking University (incl. 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"https://clinicaltrials.gov/api/v2/studies?query.spons=%22Peking+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Peking+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 52, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Peking+University%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 4, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Peking+University%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Peking+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 217, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Peking+University%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 4, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Peking+University%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 779, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Peking University\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 1145, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Peking University\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 564, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Peking University\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 13, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Peking University\"[ad] AND 2021:2025[dp]" } }, "pubsNarrow": { "gastric": { "n": 474, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Peking University Cancer Hospital\"[ad] OR \"Beijing Cancer Hospital\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 378, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Peking University Cancer Hospital\"[ad] OR \"Beijing Cancer Hospital\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 4, "completed": 217, "pct": 1.8 }, "representative": [ { "nct": "NCT07595523", "title": "Iparomlimab Tolvorlimab as Neoadjuvant Immunotherapy for Locally Advanced Gastric Adenocarcinoma With Microsatellite Instability/Mismatch Repair Deficiency", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-06-01", "conditions": [ "Gastric Cancer" ] }, { "nct": "NCT07527806", "title": "Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-05-01", "conditions": [ "Breast Cancer" ] }, { "nct": "NCT07417241", "title": "SHR-A1811 vs Pyrotinib/Capecitabine in Trastuzumab-Resistant HER2+ Advanced Breast Cancer: A Randomized Study", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-03-31", "conditions": [ "Breast Cancer", "HER2-positive Breast Cancer" ] } ], "evidence": { "total": 2, "lead": 1, "positive": 2, "negativeOrMixed": 0, "units": [ { "unit": "U-CT041", "label": "Satri-cel CT041-ST-01", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE1", "PHASE2" ] }, { "unit": "U-RESOLVE", "label": "RESOLVE · corrected comparisons and final survival follow-up", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "fuscc", "name": "Fudan University (incl. Fudan University Shanghai Cancer Center)", "country": "CN", "type": "center", "ctgov": "\"Fudan University\"", "pubmed": "\"Fudan University\"[ad]", "pubmedNarrow": "\"Fudan University Shanghai Cancer Center\"[ad]", "ctgovNarrow": "\"Fudan University\"", "unit": "University medical system: Fudan University Shanghai Medical College and its hospitals, including Fudan University Shanghai Cancer Center.", "note": { "why": "Largest breast-cancer trial portfolio in the set after the NCI, and a collaborator on the CLDN18.2 CAR-T trial.", "learn": "Running gastric and breast programmes at scale in one centre.", "collab": "None approached." }, "indicators": { "id": "fuscc", "trials": { "gastric": { "n": 39, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Fudan+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Fudan+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 178, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Fudan+University%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 40, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Fudan+University%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Fudan+University%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 138, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Fudan+University%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Fudan+University%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 762, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR 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797, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Fudan University Shanghai Cancer Center\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 3, "completed": 138, "pct": 2.2 }, "representative": [ { "nct": "NCT07419880", "title": "Re-challenge Immunotherapy With Cromolyn, TQB2102, and Panpulimab in Immune-Refractory Triple Negative Breast Cancer", "acronym": "RECLAIM", "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2027-01-01", "conditions": [ "Triple -Negative Breast Cancer" ] }, { "nct": "NCT07423611", "title": "ctDNA-Guided Chemotherapy Omission With Ribociclib Plus Endocrine Therapy in HR-Positive/HER2-Negative Breast Cancer", "acronym": "RACE", "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-10-01", "conditions": [ "Breast Cancer" ] }, { "nct": "NCT07760844", "title": "An Open-Label, Randomized Phase III Study of Trastuzumab Rezetecan With or Without Everolimus in First to Third Line LAR Subtype TNBC", "acronym": "SCHBCC-N0117", "phases": [ "PHASE3" ], "status": "NOT_YET_RECRUITING", "start": "2026-10-01", "conditions": [ "Breast Cancer", "Triple Negative Breast Cancer (TNBC)" ] } ], "evidence": { "total": 2, "lead": 1, "positive": 2, "negativeOrMixed": 0, "units": [ { "unit": "U-CT041", "label": "Satri-cel CT041-ST-01", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE1", "PHASE2" ] }, { "unit": "U-HypoMastIMNI26", "label": "HypoMast-IMNI: locoregional noninferiority and reduced acute skin toxicity", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "NA" ] } ] }, "resources": [] }, { "id": "mskcc", "name": "Memorial Sloan Kettering Cancer Center", "country": "US", "type": "center", "ctgov": "\"Memorial Sloan Kettering Cancer Center\"", "pubmed": "\"Memorial Sloan Kettering\"[ad]", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "Source of the breast cohort used in analysis A2 and of the esophagogastric genomic study behind the co-alteration hypothesis.", "learn": "Making an institutional sequencing cohort public at summary level so outsiders can re-analyse it.", "collab": "Its data are already reachable through cBioPortal; that is the working relationship this draft uses." }, "indicators": { "id": "mskcc", "trials": { "gastric": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Memorial+Sloan+Kettering+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Memorial+Sloan+Kettering+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 83, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Memorial+Sloan+Kettering+Cancer+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 4, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Memorial+Sloan+Kettering+Cancer+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Memorial+Sloan+Kettering+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 159, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Memorial+Sloan+Kettering+Cancer+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 61, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Memorial+Sloan+Kettering+Cancer+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 236, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Memorial Sloan Kettering\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 1671, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Memorial Sloan Kettering\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 135, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Memorial Sloan Kettering\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 18, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Memorial Sloan Kettering\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 61, "completed": 159, "pct": 38.4 }, "representative": [ { "nct": "NCT07818018", "title": "A Study of 2141-V11 in People With Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2026-09-04", "conditions": [ "Esophageal Cancer", "Advanced Esophageal Cancer", "Gastric Cancer" ] }, { "nct": "NCT07776613", "title": "A Study of Romosozumab in People With Breast Cancer and Osteoporosis", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2026-08-17", "conditions": [ "Breast Cancer", "Metastatic Breast Cancer (MBC)" ] }, { "nct": "NCT07768436", "title": "A Study of Cyclophosphamide, Methotrexate, Fluorouracil (CMF) for People With Breast Cancer", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2026-08-11", "conditions": [ "Adenocarcinoma of the Breast", "Breast Cancer", "Triple Negative Breast Cancer" ] } ], "evidence": { "total": 2, "lead": 2, "positive": 1, "negativeOrMixed": 0, "units": [ { "unit": "U-DOSTrectal", "label": "Dostarlimab · dMMR rectal organ preservation", "role": "lead sponsor", "result": "positive", "program": "colorectal", "phases": [ "PHASE2" ] }, { "unit": "U-OPRA", "label": "OPRA · watch-and-wait after total neoadjuvant therapy", "role": "lead sponsor", "result": "descriptive", "program": "colorectal", "phases": [ "PHASE2" ] } ] }, "resources": [ { "id": "D-MSK18", "name": "Breast Cancer (MSK, Cancer Cell 2018)", "status": "Connected", "used": [ "A2", "A5" ] }, { "id": "D-MSKEGC", "name": "MSK esophagogastric cohort (Janjigian 2018)", "status": "Planned", "used": [] } ] }, { "id": "mdacc", "name": "The University of Texas MD Anderson Cancer Center", "country": "US", "type": "center", "ctgov": "\"M.D. Anderson Cancer Center\"", "pubmed": "\"MD Anderson\"[ad]", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "Highest breast-cancer publication count in the set.", "learn": "Volume of investigator-initiated early-phase work.", "collab": "None approached." }, "indicators": { "id": "mdacc", "trials": { "gastric": { "n": 23, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22M.D.+Anderson+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22M.D.+Anderson+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 109, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22M.D.+Anderson+Cancer+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22M.D.+Anderson+Cancer+Center%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22M.D.+Anderson+Cancer+Center%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 210, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22M.D.+Anderson+Cancer+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 93, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22M.D.+Anderson+Cancer+Center%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 261, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"MD Anderson\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 1881, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"MD Anderson\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 96, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"MD Anderson\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 16, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"MD Anderson\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 93, "completed": 210, "pct": 44.3 }, "representative": [ { "nct": "NCT07610525", "title": "Blood and imagE-guided Optimization of Neoadjuvant Therapy in People With Early Stage Triple-negative Breast cancER - the BETTER Trial", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-11-05", "conditions": [ "Triple Negative Breast Cancer", "Blood and Image Guided", "Optimization of Neoadjuvant Therapy" ] }, { "nct": "NCT07509008", "title": "Phase 1/2 Window Of Opportunity Study Of TROP2 CAR/IL-15 TGFBR2 KO NK Cells Delivered Intraperitoneally For The Management Of Gastric Cancer Metastatic To The Peritoneum", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-09-01", "conditions": [ "Gastric Cancer, Metastatic" ] }, { "nct": "NCT07407920", "title": "Ph2 Study for Optimization of Adjunct Systemic Therapy in HER2+ Patients, MolecularPCR Trial", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-10-09", "conditions": [ "Anatomic Stage I Breast Cancer AJCC v8", "Anatomic Stage II Breast Cancer AJCC v8", "Early Stage HER2-Positive Breast Carcinoma" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "dfci", "name": "Dana-Farber Cancer Institute", "country": "US", "type": "center", "ctgov": "\"Dana-Farber Cancer Institute\"", "pubmed": "\"Dana-Farber\"[ad]", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "High breast-cancer output with an unusually high count on structural and computational methods among the clinical centres.", "learn": "Keeping a computational group inside a clinical cancer centre.", "collab": "None approached." }, "indicators": { "id": "dfci", "trials": { "gastric": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Dana-Farber+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Dana-Farber+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 107, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Dana-Farber+Cancer+Institute%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Dana-Farber+Cancer+Institute%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Dana-Farber+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 127, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Dana-Farber+Cancer+Institute%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 77, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Dana-Farber+Cancer+Institute%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 84, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Dana-Farber\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 1643, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Dana-Farber\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 166, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Dana-Farber\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 19, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Dana-Farber\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 77, "completed": 127, "pct": 60.6 }, "representative": [ { "nct": "NCT07499999", "title": "Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer", "acronym": "BabyTEARS", "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-09-09", "conditions": [ "Breast Cancer", "Ductal Carcinoma", "Estrogen-receptor-positive Breast Cancer" ] }, { "nct": "NCT07123649", "title": "Individualizing Approaches to Surveillance Mammography in Older Breast Cancer Survivors - The I-MAMMO Study", "acronym": "I-MAMMO", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-09-11", "conditions": [ "Breast Cancer" ] }, { "nct": "NCT06439693", "title": "The SAPPHO Study: Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2024-08-08", "conditions": [ "Breast Cancer Female", "Breast Cancer", "Breast Cancer Metastatic" ] } ], "evidence": { "total": 5, "lead": 5, "positive": 0, "negativeOrMixed": 4, "units": [ { "unit": "U-PACE", "label": "PACE · palbociclib continuation after progression", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-APT", "label": "APT · long-term outcomes after limited adjuvant chemotherapy", "role": "lead sponsor", "result": "descriptive", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-ATEMPT", "label": "ATEMPT", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-Ganetespib26", "label": "Fulvestrant with ganetespib in endocrine resistance: negative randomized phase II result", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-PaxalisibBrain26", "label": "Paxalisib plus trastuzumab: no confirmed CNS responses at the recommended dose", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE2" ] } ] }, "resources": [] }, { "id": "gustave-roussy", "name": "Gustave Roussy", "country": "FR", "type": "center", "ctgov": "\"Gustave Roussy, Cancer Campus, Grand Paris\"", "pubmed": "\"Gustave Roussy\"[ad]", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "European comprehensive centre; the ESR1-switching trial came from the French cooperative group network it sits in.", "learn": "Cooperative-group trials that test a monitoring strategy rather than a drug.", "collab": "None approached." }, "indicators": { "id": "gustave-roussy", "trials": { "gastric": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 16, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 21, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Gustave+Roussy%2C+Cancer+Campus%2C+Grand+Paris%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 33, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Gustave Roussy\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 689, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Gustave Roussy\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 24, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Gustave Roussy\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 3, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Gustave Roussy\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 0, "completed": 21, "pct": 0 }, "representative": [ { "nct": "NCT06787118", "title": "Study Assessing the Efficacy and Safety of cANnabidiol Oral Solution for Joint Pain of Adjuvant enDOcrine theRApy in Patients With Early Breast Cancer", "acronym": "PANDORA", "phases": [ "PHASE3" ], "status": "NOT_YET_RECRUITING", "start": "2025-12", "conditions": [ "Breast Cancer Stage I", "Breast Cancer Stage II", "Breast Cancer Stage III" ] }, { "nct": "NCT07159451", "title": "A Short-term Preoperative, Evaluating Activity and Safety of Elacestrant Monotherapy as Compared to Elacestrant + Ovarian Function Suppression (LHRH Agonist) in Premenopausal Patients With Stage I-II ER+/HER2- Breast Cancer", "acronym": "POP-ELA", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-10-06", "conditions": [ "Breast Cancer" ] }, { "nct": "NCT06781996", "title": "A Study to Determine the Efficacy of a Digital Self-management Support Tool to Improve the Quality of Life During Adjuvant HOrmonal Therapy for Patients With Early Breast Cancer", "acronym": "HOPE", "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-09-09", "conditions": [ "Breast Cancer", "Breast Cancer Early Stage Breast Cancer (Stage 1-3)" ] } ], "evidence": { "total": 2, "lead": 2, "positive": 2, "negativeOrMixed": 0, "units": [ { "unit": "U-T-ESTIMABL2", "label": "ESTIMABL2 · thyroidectomy with or without radioiodine in low-risk thyroid cancer", "role": "lead sponsor", "result": "positive", "program": "thyroid", "phases": [ "PHASE3" ] }, { "unit": "U-T-ESTIMABL1", "label": "ESTIMABL1 · radioiodine dose and stimulation method in low-risk thyroid cancer", "role": "lead sponsor", "result": "positive", "program": "thyroid", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "nki", "name": "Netherlands Cancer Institute", "country": "NL", "type": "center", "ctgov": "\"The Netherlands Cancer Institute\"", "pubmed": "\"Netherlands Cancer Institute\"[ad]", "unit": "Independent cancer centre without a parent university medical system of its own: counted as the centre (hospital, research institute and school under its own name).", "note": { "why": "Comprehensive centre known for de-escalation and biology-driven trial design.", "learn": "Designing trials that can return a negative answer cleanly.", "collab": "None approached." }, "indicators": { "id": "nki", "trials": { "gastric": { "n": 5, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22The+Netherlands+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22The+Netherlands+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 30, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22The+Netherlands+Cancer+Institute%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22The+Netherlands+Cancer+Institute%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22The+Netherlands+Cancer+Institute%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 33, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22The+Netherlands+Cancer+Institute%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22The+Netherlands+Cancer+Institute%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 83, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Netherlands Cancer Institute\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 845, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Netherlands Cancer Institute\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 50, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Netherlands Cancer Institute\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 2, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Netherlands Cancer Institute\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 0, "completed": 33, "pct": 0 }, "representative": [ { "nct": "NCT07786051", "title": "DiEtary Mimicry by Glucocorticoid Modulation Evaluation in ER+ Metastatic Breast Cancer Treatment: Efficacy and Response (DEMETER Trial)", "acronym": "DEMETER", "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-11-01", "conditions": [ "Breast Cancer" ] }, { "nct": "NCT07486687", "title": "Pembrolizumab Adjuvant in Patients With Early-stage Triple Negative Breast Cancer With Residual Disease After Neoadjuvant Pembrolizumab Plus Chemotherapy", "acronym": "PLANET", "phases": [ "PHASE3" ], "status": "NOT_YET_RECRUITING", "start": "2026-04", "conditions": [ "Triple Negative Breast Cancer (TNBC), Early Setting", "Early Stage Triple-Negative Breast Carcinoma", "Triple -Negative Breast Cancer" ] }, { "nct": "NCT07310758", "title": "Contrast-enhanced Ultrasound for Sentinel Node Detection", "acronym": null, "phases": [ "PHASE2", "PHASE3" ], "status": "RECRUITING", "start": "2025-09-18", "conditions": [ "Melanoma", "Breast Cancer", "Head & Neck Cancer" ] } ], "evidence": { "total": 3, "lead": 2, "positive": 1, "negativeOrMixed": 2, "units": [ { "unit": "U-NICHE2", "label": "NICHE-2 · neoadjuvant dual checkpoint blockade", "role": "lead sponsor", "result": "positive", "program": "colorectal", "phases": [ "PHASE2" ] }, { "unit": "U-CRITICS", "label": "CRITICS · postoperative chemotherapy versus chemoradiotherapy", "role": "collaborator", "result": "negative", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-TRAIN2", "label": "TRAIN-2 · anthracycline contribution with dual HER2 blockade", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "nci-us", "name": "U.S. National Cancer Institute", "country": "US", "type": "infrastructure", "ctgov": "\"National Cancer Institute (NCI)\"", "pubmed": "\"National Cancer Institute\"[ad] AND (Bethesda[ad] OR Rockville[ad] OR Frederick[ad])", "note": { "why": "Public funder and sponsor; also the source of the two reference pages this draft cites for treatment options.", "learn": "Keeping a maintained, dated, reference summary of the evidence — the model for our own Research Briefs.", "collab": "Its pages and data portals are public; no relationship needed." }, "indicators": { "id": "nci-us", "trials": { "gastric": { "n": 79, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Institute+%28NCI%29%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 6, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Institute+%28NCI%29%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 475, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Institute+%28NCI%29%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 32, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Institute+%28NCI%29%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 10, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22National+Cancer+Institute+%28NCI%29%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 149, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Institute+%28NCI%29%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 137, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22National+Cancer+Institute+%28NCI%29%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 158, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"National Cancer Institute\"[ad] AND (Bethesda[ad] OR Rockville[ad] OR Frederick[ad]) AND 2021:2025[dp]" }, "breast": { "n": 791, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"National Cancer Institute\"[ad] AND (Bethesda[ad] OR Rockville[ad] OR Frederick[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 248, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"National Cancer Institute\"[ad] AND (Bethesda[ad] OR Rockville[ad] OR Frederick[ad]) AND 2021:2025[dp]" }, "structural": { "n": 22, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"National Cancer Institute\"[ad] AND (Bethesda[ad] OR Rockville[ad] OR Frederick[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 137, "completed": 149, "pct": 91.9 }, "representative": [ { "nct": "NCT07391774", "title": "Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2026-08-10", "conditions": [ "Anatomic Stage II Breast Cancer AJCC v8", "Anatomic Stage IIIA Breast Cancer AJCC v8", "Anatomic Stage IIIC Breast Cancer AJCC v8" ] }, { "nct": "NCT06503146", "title": "18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-09-09", "conditions": [ "Sarcoma", "Small Cell Lung Cancer or Extrapulmonary Neuroendocrine Cancer (EP-NEC)", "Mesothelioma" ] }, { "nct": "NCT06195306", "title": "Low Dose Tamoxifen With or Without Omega-3 Fatty Acids for Breast Cancer Risk Reduction", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-07-28", "conditions": [ "Breast Atypical Hyperplasia", "Breast Carcinoma", "Breast Ductal Carcinoma In Situ" ] } ], "evidence": { "total": 9, "lead": 3, "positive": 3, "negativeOrMixed": 6, "units": [ { "unit": "U-EA1131", "label": "EA1131 · platinum versus capecitabine", "role": "collaborator", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-SOFT", "label": "SOFT · ovarian suppression in premenopausal early breast cancer", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-NSABPB42", "label": "NSABP B-42 · extended letrozole with long-term follow-up", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-PROSPECT", "label": "PROSPECT · FOLFOX with selective chemoradiation before surgery", "role": "collaborator", "result": "positive", "program": "colorectal", "phases": [ "PHASE2", "PHASE3" ] }, { "unit": "U-RxPONDER", "label": "RxPONDER", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-TAILORx", "label": "TAILORx", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-MOUNTAINEER", "label": "MOUNTAINEER · tucatinib plus trastuzumab in HER2-positive colorectal cancer", "role": "collaborator", "result": "positive", "program": "colorectal", "phases": [ "PHASE2" ] }, { "unit": "U-ATOMIC", "label": "ATOMIC · adjuvant atezolizumab with FOLFOX in stage III dMMR colon cancer", "role": "lead sponsor", "result": "positive", "program": "colorectal", "phases": [ "PHASE3" ] }, { "unit": "U-CALGB80405", "label": "CALGB/SWOG 80405 · cetuximab or bevacizumab with first-line chemotherapy", "role": "collaborator", "result": "negative", "program": "colorectal", "phases": [ "PHASE3" ] } ] }, "resources": [ { "id": "D-GDC", "name": "NCI Genomic Data Commons", "status": "Planned", "used": [] } ] }, { "id": "embl-ebi", "name": "EMBL's European Bioinformatics Institute (EMBL-EBI)", "country": "UK", "type": "infrastructure", "ctgov": null, "pubmed": "(\"European Bioinformatics Institute\"[ad] OR EMBL-EBI[ad])", "note": { "why": "Runs the prediction database and the training material this draft relies on for AlphaFold limits and terms.", "learn": "Publishing limits alongside a resource rather than after it.", "collab": "Public APIs are already in use here." }, "indicators": { "id": "embl-ebi", "trials": null, "pubs": { "gastric": { "n": 1, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"European Bioinformatics Institute\"[ad] OR EMBL-EBI[ad]) AND 2021:2025[dp]" }, "breast": { "n": 9, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"European Bioinformatics Institute\"[ad] OR EMBL-EBI[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 112, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"European Bioinformatics Institute\"[ad] OR EMBL-EBI[ad]) AND 2021:2025[dp]" }, "structural": { "n": 3, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"European Bioinformatics Institute\"[ad] OR EMBL-EBI[ad]) AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [ { "id": "D-AFDB", "name": "AlphaFold Protein Structure Database", "status": "Connected", "used": [ "Structure Lab" ] } ] }, { "id": "sanger", "name": "Wellcome Sanger Institute", "country": "UK", "type": "infrastructure", "ctgov": null, "pubmed": "(\"Wellcome Sanger Institute\"[ad] OR \"Wellcome Trust Sanger Institute\"[ad])", "note": { "why": "Genomics infrastructure institute; reference point for what large-scale sequence resources look like.", "learn": "Long-horizon resource building.", "collab": "None approached." }, "indicators": { "id": "sanger", "trials": null, "pubs": { "gastric": { "n": 5, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Wellcome Sanger Institute\"[ad] OR \"Wellcome Trust Sanger Institute\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 28, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Wellcome Sanger Institute\"[ad] OR \"Wellcome Trust Sanger Institute\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 19, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"Wellcome Sanger Institute\"[ad] OR \"Wellcome Trust Sanger Institute\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"Wellcome Sanger Institute\"[ad] OR \"Wellcome Trust Sanger Institute\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "broad", "name": "Broad Institute of MIT and Harvard", "country": "US", "type": "infrastructure", "ctgov": null, "pubmed": "\"Broad Institute\"[ad]", "note": { "why": "Source of the dependency-map and cell-line resources this draft lists as planned data.", "learn": "Pairing a data resource with the analysis tooling that makes it usable.", "collab": "Portals are public; terms not yet reviewed by RISCON Labs." }, "indicators": { "id": "broad", "trials": null, "pubs": { "gastric": { "n": 33, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Broad Institute\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 187, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Broad Institute\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 139, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Broad Institute\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 12, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Broad Institute\"[ad] AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [ { "id": "D-DEPMAP", "name": "DepMap / CCLE", "status": "Planned", "used": [] } ] }, { "id": "rcsb", "name": "RCSB Protein Data Bank", "country": "US", "type": "infrastructure", "ctgov": null, "pubmed": "(\"RCSB Protein Data Bank\"[ad] OR \"Research Collaboratory for Structural Bioinformatics\"[ad])", "note": { "why": "Runs the structure archive and search APIs this draft queries for every structure count.", "learn": "Stable identifiers and an API that makes a claim re-checkable years later.", "collab": "Public APIs are already in use here." }, "indicators": { "id": "rcsb", "trials": null, "pubs": { "gastric": { "n": 0, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"RCSB Protein Data Bank\"[ad] OR \"Research Collaboratory for Structural Bioinformatics\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 1, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"RCSB Protein Data Bank\"[ad] OR \"Research Collaboratory for Structural Bioinformatics\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 45, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"RCSB Protein Data Bank\"[ad] OR \"Research Collaboratory for Structural Bioinformatics\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 1, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"RCSB Protein Data Bank\"[ad] OR \"Research Collaboratory for Structural Bioinformatics\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [ { "id": "D-PDB", "name": "RCSB Protein Data Bank", "status": "Connected", "used": [ "Structure Lab" ] } ] }, { "id": "deepmind", "name": "Google DeepMind", "country": "UK", "type": "infrastructure", "ctgov": null, "pubmed": "DeepMind[ad]", "note": { "why": "Author of the prediction methods and the terms that decide what this draft may automate.", "learn": "That a method's licence, not its accuracy, can be the binding constraint on a research plan (QP-12).", "collab": "None; terms govern use." }, "indicators": { "id": "deepmind", "trials": null, "pubs": { "gastric": { "n": 0, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND DeepMind[ad] AND 2021:2025[dp]" }, "breast": { "n": 2, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND DeepMind[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 21, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND DeepMind[ad] AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND DeepMind[ad] AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [ { "id": "D-AFDB", "name": "AlphaFold Protein Structure Database", "status": "Connected", "used": [ "Structure Lab" ] } ] }, { "id": "ipd", "name": "Institute for Protein Design, University of Washington", "country": "US", "type": "infrastructure", "ctgov": null, "pubmed": "\"Institute for Protein Design\"[ad]", "note": { "why": "Protein-design group; the boundary between reading structures and designing molecules.", "learn": "What a design programme requires before it is worth starting.", "collab": "None approached." }, "indicators": { "id": "ipd", "trials": null, "pubs": { "gastric": { "n": 0, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Institute for Protein Design\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 0, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Institute for Protein Design\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 121, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Institute for Protein Design\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 1, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Institute for Protein Design\"[ad] AND 2021:2025[dp]" } } }, "postingRate": null, "representative": null, "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "roche", "name": "Roche (incl. Genentech)", "country": "CH", "type": "industry", "ctgov": "\"Hoffmann-La Roche\" OR \"Genentech, Inc.\"", "pubmed": "(Genentech[ad] OR \"Hoffmann-La Roche\"[ad] OR \"Roche Pharma\"[ad] OR \"Roche Products\"[ad] OR \"Roche Diagnostics\"[ad])", "note": { "why": "Sponsor of the largest number of curated units in this library, positive and negative alike.", "learn": "How a single sponsor's programme reads when its failures are listed beside its successes.", "collab": "Not applicable at this stage." }, "indicators": { "id": "roche", "trials": { "gastric": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 1, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 97, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 28, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 16, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 352, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 211, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Hoffmann-La+Roche%22+OR+%22Genentech%2C+Inc.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 15, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (Genentech[ad] OR \"Hoffmann-La Roche\"[ad] OR \"Roche Pharma\"[ad] OR \"Roche Products\"[ad] OR \"Roche Diagnostics\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 274, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (Genentech[ad] OR \"Hoffmann-La Roche\"[ad] OR \"Roche Pharma\"[ad] OR \"Roche Products\"[ad] OR \"Roche Diagnostics\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 131, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (Genentech[ad] OR \"Hoffmann-La Roche\"[ad] OR \"Roche Pharma\"[ad] OR \"Roche Products\"[ad] OR \"Roche Diagnostics\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 7, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (Genentech[ad] OR \"Hoffmann-La Roche\"[ad] OR \"Roche Pharma\"[ad] OR \"Roche Products\"[ad] OR \"Roche Diagnostics\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 211, "completed": 352, "pct": 59.9 }, "representative": [ { "nct": "NCT07748208", "title": "A Study Evaluating the Safety of Inavolisib and Fulvestrant With or Without Palbociclib in Participants With Advanced Breast Cancer (ABC) and Type 2 Diabetes", "acronym": null, "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-10-30", "conditions": [ "Breast Cancer", "Diabetes Type II" ] }, { "nct": "NCT07827573", "title": "A Study to Learn How Well Participants With a Specific Type of Early Breast Cancer (ER-Positive, HER2-Negative) Tolerate and Stay on Treatment With Giredestrant and How They Feel During Treatment", "acronym": "kalitERA", "phases": [ "PHASE3" ], "status": 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"negative", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-CLASSIC", "label": "CLASSIC", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-CLEOPATRA", "label": "CLEOPATRA", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-EMILIA", "label": "EMILIA", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-INAVO120", "label": "INAVO120", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE2", "PHASE3" ] }, { "unit": "U-IMP130", "label": "IMpassion130", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-IMP131", "label": "IMpassion131", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-KATHERINE", "label": "KATHERINE · long-term residual-disease follow-up", "role": "lead 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"program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-APHINITY", "label": "APHINITY · adjuvant pertuzumab added to trastuzumab and chemotherapy", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-KRISTINE", "label": "KRISTINE · neoadjuvant T-DM1 plus pertuzumab without conventional chemotherapy", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-T-ARROW", "label": "ARROW (pralsetinib, RET-altered thyroid cohorts)", "role": "lead sponsor", "result": "positive", "program": "thyroid", "phases": [ "PHASE1", "PHASE2" ] }, { "unit": "U-IM050", "label": "IMpassion050: primary response and final follow-up", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "astrazeneca", "name": "AstraZeneca", "country": "UK", "type": "industry", "ctgov": "\"AstraZeneca\"", "pubmed": "AstraZeneca[ad]", "note": { "why": 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"conditions": [ "Advanced Breast Cancer" ] }, { "nct": "NCT07431281", "title": "Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2026-02-03", "conditions": [ "Gastric Cancer", "Gastroesophageal Junction Adenocarcinoma", "Esophageal Cancer" ] } ], "evidence": { "total": 24, "lead": 14, "positive": 16, "negativeOrMixed": 7, "units": [ { "unit": "U-DG01", "label": "DESTINY-Gastric01", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE2" ] }, { "unit": "U-DG02", "label": "DESTINY-Gastric02", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE2" ] }, { "unit": "U-DG04", "label": "DESTINY-Gastric04", "role": "collaborator", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-DPT02", "label": "DESTINY-PanTumor02", "role": "lead sponsor", "result": "positive", "program": "expansion", "phases": [ "PHASE2" ] }, { "unit": "U-DB03", "label": "DESTINY-Breast03", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB04", "label": "DESTINY-Breast04", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB06", "label": "DESTINY-Breast06", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB09", "label": "DESTINY-Breast09", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-CAP291", "label": "CAPItello-291", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-SERENA6", "label": "SERENA-6", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-TROPIONB01", "label": "TROPION-Breast01", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-OlympiA", "label": "OlympiA", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-MATTERHORN", "label": "MATTERHORN", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-DB05", "label": "DESTINY-Breast05", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-SALSA", "label": "ABCSG-16/SALSA", "role": "lead sponsor", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB08", "label": "DESTINY-Breast08", "role": "lead sponsor", "result": "descriptive", "program": "breast", "phases": [ "PHASE1" ] }, { "unit": "U-OlympiAD", "label": "OlympiAD · olaparib in germline-BRCA metastatic breast cancer", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-TROPIONB02", "label": "TROPION-Breast02", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB11", "label": "DESTINY-Breast11 · neoadjuvant HER2 regimen comparison", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DCRC01", "label": "DESTINY-CRC01 · trastuzumab deruxtecan by HER2 expression level in colorectal cancer", "role": "collaborator", "result": "mixed", "program": "colorectal", "phases": [ "PHASE2" ] }, { "unit": "U-DB02", "label": "DESTINY-Breast02", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-PALOMA3", "label": "PALOMA-3 · palbociclib plus fulvestrant after endocrine therapy", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-T-ASTRA", "label": "ASTRA · selumetinib added to adjuvant radioactive iodine in high-risk differentiated thyroid cancer", "role": "lead sponsor", "result": "negative", "program": "thyroid", "phases": [ "PHASE3" ] }, { "unit": "U-DCRC02", "label": "DESTINY-CRC02 · two doses of trastuzumab deruxtecan in HER2-positive colorectal cancer", "role": "collaborator", "result": "positive", "program": "colorectal", "phases": [ "PHASE2" ] } ] }, "resources": [] }, { "id": "daiichi", "name": "Daiichi Sankyo", "country": "JP", "type": "industry", "ctgov": "\"Daiichi Sankyo\"", "pubmed": "\"Daiichi Sankyo\"[ad]", "note": { "why": "Originator of the HER2 ADC that appears in both cancers in this library.", "learn": "A payload and linker platform carried across targets.", "collab": "Not applicable at this stage." }, "indicators": { "id": "daiichi", "trials": { "gastric": { "n": 17, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Daiichi+Sankyo%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Daiichi+Sankyo%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 53, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Daiichi+Sankyo%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 16, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Daiichi+Sankyo%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 7, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Daiichi+Sankyo%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 75, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Daiichi+Sankyo%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 42, "url": 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or Metastatic Breast Cancer" ] }, { "nct": "NCT06731478", "title": "Study of TDXd, Chemotherapy, Pembrolizumab, and Trastuzumab in First-Line Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-02-27", "conditions": [ "Gastric Cancer", "Gastroesophageal Junction Cancer" ] } ], "evidence": { "total": 17, "lead": 9, "positive": 13, "negativeOrMixed": 3, "units": [ { "unit": "U-DG01", "label": "DESTINY-Gastric01", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE2" ] }, { "unit": "U-DG02", "label": "DESTINY-Gastric02", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE2" ] }, { "unit": "U-DG04", "label": "DESTINY-Gastric04", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-DPT02", "label": "DESTINY-PanTumor02", "role": "collaborator", "result": "positive", "program": "expansion", "phases": [ "PHASE2" ] }, { "unit": "U-DB03", "label": "DESTINY-Breast03", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB04", "label": "DESTINY-Breast04", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB06", "label": "DESTINY-Breast06", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB09", "label": "DESTINY-Breast09", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-TROPIONB01", "label": "TROPION-Breast01", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB05", "label": "DESTINY-Breast05", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DAISY", "label": "DAISY", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-DB08", "label": "DESTINY-Breast08", "role": "collaborator", "result": "descriptive", "program": "breast", "phases": [ "PHASE1" ] }, { "unit": "U-TROPIONB02", "label": "TROPION-Breast02", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DB11", "label": "DESTINY-Breast11 · neoadjuvant HER2 regimen comparison", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DCRC01", "label": "DESTINY-CRC01 · trastuzumab deruxtecan by HER2 expression level in colorectal cancer", "role": "lead sponsor", "result": "mixed", "program": "colorectal", "phases": [ "PHASE2" ] }, { "unit": "U-DB02", "label": "DESTINY-Breast02", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-DCRC02", "label": "DESTINY-CRC02 · two doses of trastuzumab deruxtecan in HER2-positive colorectal cancer", "role": "lead sponsor", "result": "positive", "program": "colorectal", "phases": [ "PHASE2" ] } ] }, "resources": [] }, { "id": "astellas", "name": "Astellas Pharma", "country": "JP", "type": "industry", "ctgov": "\"Astellas Pharma\"", "pubmed": "Astellas[ad]", "note": { "why": "Sponsor of both CLDN18.2 antibody phase 3 trials, the first target in this library that is gastric-first.", "learn": "Developing a target where gastric cancer is the lead indication rather than an extension.", "collab": "Not applicable at this stage." }, "indicators": { "id": "astellas", "trials": { "gastric": { "n": 10, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Astellas+Pharma%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Astellas+Pharma%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Astellas+Pharma%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Astellas+Pharma%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Astellas+Pharma%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 116, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Astellas+Pharma%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 43, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Astellas+Pharma%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 25, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND Astellas[ad] AND 2021:2025[dp]" }, "breast": { "n": 10, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND Astellas[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 5, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND Astellas[ad] AND 2021:2025[dp]" }, "structural": { "n": 2, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND Astellas[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 43, "completed": 116, "pct": 37.1 }, "representative": [ { "nct": "NCT07673887", "title": "A Study of ASP2138 Together With Chemotherapy and Pembrolizumab in Adults With Gastric Cancer", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2026-06-30", "conditions": [ "Gastric Adenocarcinoma", "Gastroesophageal Junction (GEJ) Adenocarcinoma" ] }, { "nct": "NCT07488676", "title": "A Study of ASP546C in Adults With Gastroesophageal Cancer, Pancreatic Cancer or Other Solid Tumors", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2026-05-04", "conditions": [ "Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma", "Pancreatic Adenocarcinoma" ] }, { "nct": "NCT07287995", "title": "A Study of ASP2998 Given by Itself and Given With Standard Therapies in People With Solid Tumors", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2026-02-05", "conditions": [ "Locally Advanced or Metastatic Malignant Solid Tumors" ] } ], "evidence": { "total": 2, "lead": 2, "positive": 2, "negativeOrMixed": 0, "units": [ { "unit": "U-SPOTLIGHT", "label": "SPOTLIGHT", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-GLOW", "label": "GLOW", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "msd", "name": "Merck & Co. (MSD)", "country": "US", "type": "industry", "ctgov": "\"Merck Sharp & Dohme LLC\"", "pubmed": "(\"Merck & Co\"[ad] OR \"Merck Sharp & Dohme\"[ad])", "note": { "why": "Sponsor of the PD-1 trials that produced both the positive first-line and the negative second-line results.", "learn": "Reading a biomarker cut-off across several trials of the same drug.", "collab": "Not applicable at this stage." }, "indicators": { "id": "msd", "trials": { "gastric": { "n": 54, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Merck+Sharp+%26+Dohme+LLC%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 10, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Merck+Sharp+%26+Dohme+LLC%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 125, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Merck+Sharp+%26+Dohme+LLC%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 11, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Merck+Sharp+%26+Dohme+LLC%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Merck+Sharp+%26+Dohme+LLC%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 324, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Merck+Sharp+%26+Dohme+LLC%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 275, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Merck+Sharp+%26+Dohme+LLC%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 36, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND (\"Merck & Co\"[ad] OR \"Merck Sharp & Dohme\"[ad]) AND 2021:2025[dp]" }, "breast": { "n": 100, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND (\"Merck & Co\"[ad] OR \"Merck Sharp & Dohme\"[ad]) AND 2021:2025[dp]" }, "structuralAny": { "n": 60, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND (\"Merck & Co\"[ad] OR \"Merck Sharp & Dohme\"[ad]) AND 2021:2025[dp]" }, "structural": { "n": 1, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND (\"Merck & Co\"[ad] OR \"Merck Sharp & Dohme\"[ad]) AND 2021:2025[dp]" } } }, "postingRate": { "posted": 275, "completed": 324, "pct": 84.9 }, "representative": [ { "nct": "NCT07060807", "title": "A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-07-21", "conditions": [ "Breast Neoplasms" ] }, { "nct": "NCT06966700", "title": "A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-06-30", "conditions": [ "Breast Neoplasms", "Triple Negative Breast Neoplasms", "HR Low-Positive/HER2-Negative Breast Neoplasms" ] }, { "nct": "NCT06829199", "title": "A Clinical Study of Boserolimab (MK-5890) With Pembrolizumab and Chemotherapy in People With Early Triple-Negative Breast Cancer (MK-5890-003)", "acronym": null, "phases": [ "PHASE2" ], "status": "WITHDRAWN", "start": "2025-03-26", "conditions": [ "Early Triple Negative Breast Cancer" ] } ], "evidence": { "total": 17, "lead": 10, "positive": 5, "negativeOrMixed": 11, "units": [ { "unit": "U-KN811", "label": "KEYNOTE-811", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-KN859", "label": "KEYNOTE-859", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-KN061", "label": "KEYNOTE-061", "role": "lead sponsor", "result": "negative", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-KN062", "label": "KEYNOTE-062", "role": "lead sponsor", "result": "mixed", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-KN522", "label": "KEYNOTE-522", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-OlympiA", "label": "OlympiA", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-cTRAKTN", "label": "c-TRAK TN · ctDNA surveillance and triggered intervention", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-KN177", "label": "KEYNOTE-177 · final analysis and long-term follow-up", "role": "lead sponsor", "result": "mixed", "program": "colorectal", "phases": [ "PHASE3" ] }, { "unit": "U-ASCENT04", "label": "ASCENT-04 / KEYNOTE-D19", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-KN585", "label": "KEYNOTE-585 · perioperative pembrolizumab", "role": "lead sponsor", "result": "mixed", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-OlympiAD", "label": "OlympiAD · olaparib in germline-BRCA metastatic breast cancer", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-NeoPACT", "label": "NeoPACT · single-arm anthracycline-free chemoimmunotherapy", "role": "collaborator", "result": "descriptive", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-KN355", "label": "KEYNOTE-355 · pembrolizumab plus chemotherapy by PD-L1 score", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-KN756", "label": "KEYNOTE-756 · neoadjuvant pembrolizumab in ER-positive early breast cancer", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-LEAP017", "label": "LEAP-017 · lenvatinib plus pembrolizumab in previously treated pMMR colorectal cancer", "role": "lead sponsor", "result": "negative", "program": "colorectal", "phases": [ "PHASE3" ] }, { "unit": "U-T-LENVA211", "label": "Study 211 · lenvatinib starting dose 18 mg versus 24 mg in radioiodine-refractory thyroid cancer", "role": "collaborator", "result": "negative", "program": "thyroid", "phases": [ "PHASE2" ] }, { "unit": "U-INTEGRAL26", "label": "INTEGRAL: early termination of intratumoral IL-12 combination in anthracycline-refractory TNBC", "role": "collaborator", "result": "negative", "program": "breast", "phases": [ "PHASE2" ] } ] }, "resources": [] }, { "id": "lilly", "name": "Eli Lilly and Company", "country": "US", "type": "industry", "ctgov": "\"Eli Lilly and Company\"", "pubmed": "\"Eli Lilly\"[ad]", "note": { "why": "Sponsor of the VEGFR2 and adjuvant CDK4/6 programmes, including one trial that split PFS from survival.", "learn": "What it looks like when one endpoint moves and the other does not.", "collab": "Not applicable at this stage." }, "indicators": { "id": "lilly", "trials": { "gastric": { "n": 12, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Eli+Lilly+and+Company%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Eli+Lilly+and+Company%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 58, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Eli+Lilly+and+Company%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 8, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Eli+Lilly+and+Company%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 6, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Eli+Lilly+and+Company%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 510, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Eli+Lilly+and+Company%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 355, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Eli+Lilly+and+Company%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 22, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND \"Eli Lilly\"[ad] AND 2021:2025[dp]" }, "breast": { "n": 150, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND \"Eli Lilly\"[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 23, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Eli Lilly\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Eli Lilly\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 355, "completed": 510, "pct": 69.6 }, "representative": [ { "nct": "NCT07287098", "title": "A Study of Imlunestrant (LY3484356) in Premenopausal Women With Estrogen Receptor-Positive (ER+) Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Early Breast Cancer", "acronym": "preEMBER", "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2026-05-13", "conditions": [ "Breast Neoplasms" ] }, { "nct": "NCT07174336", "title": "A Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-12-22", "conditions": [ "Breast Neoplasms", "Neoplasm Metastasis" ] }, { "nct": "NCT05768139", "title": "First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors", "acronym": "PIKALO-1", "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2023-04-17", "conditions": [ "Breast Cancer", "Solid Tumors, Adult" ] } ], "evidence": { "total": 10, "lead": 8, "positive": 8, "negativeOrMixed": 2, "units": [ { "unit": "U-RAINBOW", "label": "RAINBOW", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-REGARD", "label": "REGARD", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-RAINFALL", "label": "RAINFALL", "role": "lead sponsor", "result": "mixed", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-monarchE", "label": "monarchE", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-EMBER3", "label": "EMBER-3", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-T-LIBRETTO531", "label": "LIBRETTO-531", "role": "collaborator", "result": "positive", "program": "thyroid", "phases": [ "PHASE3" ] }, { "unit": "U-T-LIBRETTO001", "label": "LIBRETTO-001 (thyroid cohorts)", "role": "lead sponsor", "result": "positive", "program": "thyroid", "phases": [ "PHASE1", "PHASE2" ] }, { "unit": "U-postMONARCH", "label": "postMONARCH · abemaciclib after CDK4/6 progression", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-MONARCH2", "label": "MONARCH 2 · abemaciclib plus fulvestrant after endocrine therapy", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-BREAKWATER", "label": "BREAKWATER · first-line encorafenib, cetuximab and mFOLFOX6 in BRAF V600E colorectal cancer", "role": "collaborator", "result": "positive", "program": "colorectal", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "novartis", "name": "Novartis", "country": "CH", "type": "industry", "ctgov": "\"Novartis Pharmaceuticals\" OR \"Novartis\"", "pubmed": "Novartis[ad]", "note": { "why": "Sponsor of the first PI3Kα inhibitor trial and of an adjuvant CDK4/6 trial with a positive result.", "learn": "Carrying a target from a discovery paper to a phase 3 population definition.", "collab": "Not applicable at this stage." }, "indicators": { "id": "novartis", "trials": { "gastric": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 2, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 89, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 16, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 5, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 373, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 295, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Novartis+Pharmaceuticals%22+OR+%22Novartis%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 7, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND Novartis[ad] AND 2021:2025[dp]" }, "breast": { "n": 185, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND Novartis[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 68, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND Novartis[ad] AND 2021:2025[dp]" }, "structural": { "n": 6, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND Novartis[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 295, "completed": 373, "pct": 79.1 }, "representative": [ { "nct": "NCT07679269", "title": "Roll-Over Study of Alpelisib (BYL719) for Continued Access and Long-Term Safety.", "acronym": "EPIK-RO", "phases": [ "PHASE2" ], "status": "NOT_YET_RECRUITING", "start": "2026-12-15", "conditions": [ "PIK3CA-Related Overgrowth Spectrum (PROS)", "Breast Neoplasms (Including Advanced or Metastatic Breast Cancer With PIK3CA Mutation)" ] }, { "nct": "NCT07570966", "title": "Study of ERW316 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "WITHDRAWN", "start": "2026-06-30", "conditions": [ "Advanced HR+/HER2- Breast Cancer", "Advanced CCNE1-amplified Solid Tumors", "Metastatic Castration-resistant Prostate Cancer (mCRPC)" ] }, { "nct": "NCT07288359", "title": "Study of GVV858 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "RECRUITING", "start": "2025-12-29", "conditions": [ "Advanced HR+/HER2- Breast Cancer", "Advanced CCNE1-amplified Solid Tumors", "Metastatic Castration-resistant Prostate Cancer" ] } ], "evidence": { "total": 10, "lead": 7, "positive": 7, "negativeOrMixed": 3, "units": [ { "unit": "U-LOGiC", "label": "LOGiC", "role": "lead sponsor", "result": "negative", "program": "gastric", "phases": [ "PHASE3" ] }, { "unit": "U-NATALEE", "label": "NATALEE", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-SOLAR1", "label": "SOLAR-1", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-T-ROAR", "label": "ROAR (anaplastic thyroid cohort)", "role": "lead sponsor", "result": "positive", "program": "thyroid", "phases": [ "PHASE2" ] }, { "unit": "U-MAINTAIN", "label": "MAINTAIN · endocrine switch with ribociclib", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE2" ] }, { "unit": "U-NSABPB42", "label": "NSABP B-42 · extended letrozole with long-term follow-up", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-MINDACT", "label": "MINDACT", "role": "collaborator", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-ML2", "label": "MONALEESA-2 · first-line ribociclib plus letrozole", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-ML7", "label": "MONALEESA-7 · ribociclib plus endocrine therapy before menopause", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-ML3", "label": "MONALEESA-3 · ribociclib plus fulvestrant", "role": "lead sponsor", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "pfizer", "name": "Pfizer", "country": "US", "type": "industry", "ctgov": "\"Pfizer\"", "pubmed": "Pfizer[ad]", "note": { "why": "Sponsor or partner on the CDK4/6 trials that failed in the adjuvant setting while two competitors succeeded.", "learn": "The clearest case in this library of a class effect that did not hold (QP-04).", "collab": "Not applicable at this stage." }, "indicators": { "id": "pfizer", "trials": { "gastric": { "n": 15, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Pfizer%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Pfizer%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 139, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Pfizer%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 16, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Pfizer%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 5, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Pfizer%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 483, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Pfizer%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 328, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22Pfizer%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 7, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND Pfizer[ad] AND 2021:2025[dp]" }, "breast": { "n": 295, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND Pfizer[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 52, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND Pfizer[ad] AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND 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"NCT06966453", "title": "A Study of Disitamab Vedotin in Adults With HER2 Expressing Advanced Breast Cancer", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "ACTIVE_NOT_RECRUITING", "start": "2025-06-30", "conditions": [ "Breast Cancer", "Breast Neoplasms" ] } ], "evidence": { "total": 14, "lead": 8, "positive": 5, "negativeOrMixed": 9, "units": [ { "unit": "U-PALLAS", "label": "PALLAS", "role": "collaborator", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-PENELOPEB", "label": "PENELOPE-B", "role": "collaborator", "result": "negative", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-PADA1", "label": "PADA-1", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-VERITAC2", "label": "VERITAC-2", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-HER2CLIMB05", "label": "HER2CLIMB-05 · first-line maintenance", "role": "lead 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"label": "PATINA · palbociclib added to maintenance HER2 and endocrine therapy", "role": "collaborator", "result": "positive", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-BREAKWATER", "label": "BREAKWATER · first-line encorafenib, cetuximab and mFOLFOX6 in BRAF V600E colorectal cancer", "role": "lead sponsor", "result": "positive", "program": "colorectal", "phases": [ "PHASE3" ] }, { "unit": "U-PALOMA2", "label": "PALOMA-2 · first-line palbociclib plus letrozole", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] }, { "unit": "U-HER2CLIMB02", "label": "HER2CLIMB-02 · tucatinib added to T-DM1", "role": "lead sponsor", "result": "mixed", "program": "breast", "phases": [ "PHASE3" ] } ] }, "resources": [] }, { "id": "relay", "name": "Relay Therapeutics", "country": "US", "type": "industry", "ctgov": "\"Relay Therapeutics, Inc.\"", "pubmed": "\"Relay Therapeutics\"[ad]", "note": { "why": "Small company whose published work is a computational-structural argument for a mutant-selective inhibitor.", "learn": "The closest model in this set to what a small computational group can produce and publish.", "collab": "Not applicable at this stage." }, "indicators": { "id": "relay", "trials": { "gastric": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Relay+Therapeutics%2C+Inc.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22Relay+Therapeutics%2C+Inc.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 3, "url": 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alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND \"Relay Therapeutics\"[ad] AND 2021:2025[dp]" }, "structural": { "n": 1, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND \"Relay Therapeutics\"[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 0, "completed": 1, "pct": 0 }, "representative": [ { "nct": "NCT06982521", "title": "Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer", "acronym": "ReDiscover-2", "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2025-08-26", "conditions": [ "PIK3CA Mutation", "HER2- Negative Breast Cancer", "Hormone Receptor Positive Tumor" ] } ], "evidence": { "total": 1, "lead": 1, "positive": 0, "negativeOrMixed": 0, "units": [ { "unit": "U-RLY2608", "label": "RLY-2608", "role": "lead sponsor", "result": "descriptive", "program": "breast", "phases": [ "PHASE1" ] } ] }, "resources": [] }, { "id": "remegen", "name": "RemeGen", "country": "CN", "type": "industry", "ctgov": "\"RemeGen Co., Ltd.\"", "pubmed": "RemeGen[ad]", "note": { "why": "HER2 ADC developer running gastric and breast trials from a single-country base.", "learn": "Reaching phase 3 on a smaller portfolio.", "collab": "Not applicable at this stage." }, "indicators": { "id": "remegen", "trials": { "gastric": { "n": 9, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22RemeGen+Co.%2C+Ltd.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 4, "url": 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"https://clinicaltrials.gov/api/v2/studies?query.spons=%22RemeGen+Co.%2C+Ltd.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 25, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22RemeGen+Co.%2C+Ltd.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22RemeGen+Co.%2C+Ltd.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 3, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND RemeGen[ad] AND 2021:2025[dp]" }, "breast": { "n": 6, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND RemeGen[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 1, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND RemeGen[ad] AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND RemeGen[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 0, "completed": 25, "pct": 0 }, "representative": [ { "nct": "NCT07315750", "title": "A Study of Disitamab Vedotin Combined With Trastuzumab and Tislelizumab Versus Chemotherapy Combined With Trastuzumab With or Without Pembrolizumab in HER2-high Expression Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.", "acronym": null, "phases": [ "PHASE3" ], "status": "RECRUITING", "start": "2026-01-12", "conditions": [ "Gastric Carcinoma" ] }, { "nct": "NCT06944496", "title": "A Study of Disitamab Vedotin Combined With Tislelizumab and Chemotherapy Versus Tislelizumab Combined With Chemotherapy in HER2-Low Advanced Gastric or Gastroesophageal Junction Adenocarcinoma", "acronym": null, "phases": [ "PHASE3" ], "status": "NOT_YET_RECRUITING", "start": "2025-05-15", "conditions": [ "Gastric Carcinoma" ] }, { "nct": "NCT06642545", "title": "Efficacy and Safety Study of Disitamab Vedotin + RC148 vs. Albumin-Paclitaxone ± Toripalimab in HR-/HER2-low Breast Cancer", "acronym": null, "phases": [ "PHASE2" ], "status": "RECRUITING", "start": "2025-02-10", "conditions": [ "Breast Cancer" ] } ], "evidence": { "total": 0, "lead": 0, "positive": 0, "negativeOrMixed": 0, "units": [] }, "resources": [] }, { "id": "carsgen", "name": "CARsgen Therapeutics", "country": "CN", "type": "industry", "ctgov": "\"CARsgen Therapeutics Co., Ltd.\"", "pubmed": "CARsgen[ad]", "note": { "why": "Sponsor of the CLDN18.2 CAR-T trial, the only cell therapy in this library.", "learn": "Bringing a cell therapy into a randomised comparison in a solid tumour.", "collab": "Not applicable at this stage." }, "indicators": { "id": "carsgen", "trials": { "gastric": { "n": 5, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "gastricPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "breast": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D" }, "breastPh3": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&query.cond=breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3" }, "ph3WithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.spons=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&query.cond=%28gastric+cancer+OR+stomach+cancer+OR+gastroesophageal+junction+adenocarcinoma%29+OR+breast+cancer&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2025-12-31%5D+AND+AREA%5BPhase%5DPHASE3&aggFilters=results%3Awith" }, "completedLead": { "n": 3, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D" }, "completedLeadWithResults": { "n": 0, "url": "https://clinicaltrials.gov/api/v2/studies?query.lead=%22CARsgen+Therapeutics+Co.%2C+Ltd.%22&filter.overallStatus=COMPLETED&filter.advanced=AREA%5BStudyType%5DINTERVENTIONAL+AND+AREA%5BStartDate%5DRANGE%5B2016-01-01%2C2023-12-31%5D&aggFilters=results%3Awith" } }, "pubs": { "gastric": { "n": 6, "term": "(stomach neoplasms[mh] OR gastric cancer[tiab] OR gastric adenocarcinoma[tiab]) AND CARsgen[ad] AND 2021:2025[dp]" }, "breast": { "n": 4, "term": "(breast neoplasms[mh] OR breast cancer[tiab]) AND CARsgen[ad] AND 2021:2025[dp]" }, "structuralAny": { "n": 0, "term": "(cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND CARsgen[ad] AND 2021:2025[dp]" }, "structural": { "n": 0, "term": "((cryoelectron microscopy[mh] OR crystallography, x-ray[mh] OR protein conformation[mh] OR molecular dynamics simulation[mh] OR alphafold[tiab] OR \"protein structure prediction\"[tiab]) AND neoplasms[mh]) AND CARsgen[ad] AND 2021:2025[dp]" } } }, "postingRate": { "posted": 0, "completed": 3, "pct": 0 }, "representative": [ { "nct": "NCT04404595", "title": "Claudin18.2 CAR-T (CT041) in Patients With Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "ACTIVE_NOT_RECRUITING", "start": "2020-10-23", "conditions": [ "Gastric Cancer", "Pancreatic Cancer" ] }, { "nct": "NCT04581473", "title": "Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection", "acronym": null, "phases": [ "PHASE1", "PHASE2" ], "status": "ACTIVE_NOT_RECRUITING", "start": "2020-10-23", "conditions": [ "Gastric Adenocarcinoma", "Pancreatic Cancer", "Gastroesophageal Junction Adenocarcinoma" ] } ], "evidence": { "total": 1, "lead": 1, "positive": 1, "negativeOrMixed": 0, "units": [ { "unit": "U-CT041", "label": "Satri-cel CT041-ST-01", "role": "lead sponsor", "result": "positive", "program": "gastric", "phases": [ "PHASE1", "PHASE2" ] } ] }, "resources": [] } ], "self": { "id": "riscon", "name": "RISCON Labs", "country": "KR", "type": "independent", "ctgov": "\"RISCON\"", "pubmed": "RISCON[ad]", "standing": "Not Assessed", "reason": "RISCON Labs has no clinical trial, publication or released dataset counted in the indicators used here. All of its counts are zero, measured with the same queries as every other row.", "whatItHas": [ "Three executed descriptive analyses on open data (A1, A2, A3), with scripts that re-run and re-verify them.", "A curated evidence library where every claim carries the identifier it came from and the date it was checked.", "A working pipeline that re-fetches every cited identifier from its source." ], "whatWouldMakeItAssessable": [ { "area": "Open & Reproducible Research", "need": "Publish the analysis scripts and the derived tables under a licence, with a citable record." }, { "area": "Structural Research", "need": "Produce one structural observation that is not simply read from a database — for example the contact-residue map requested in SD-CLDN18." }, { "area": "Gastric / Breast Research", "need": "A peer-reviewed publication with a RISCON Labs affiliation; the benchmark query is affiliation-based." }, { "area": "Translational Progress", "need": "Not reachable from the current position. It requires laboratory or clinical collaboration, and none exists." } ], "refuse": "No score is assigned to RISCON Labs on any axis, and zero counts are reported as \"not measured yet\", not as a low score." } }, "rankings": [ { "id": "RK-G", "name": "Gastric Cancer Research", "applies": [ "center", "industry", "infrastructure" ], "indicators": [ { "key": "pubs.gastric", "label": "Gastric publications 2021–2025", "source": "PubMed, affiliation + topic query" }, { "key": "trials.gastric", "label": "Gastric trials started 2016–2025", "source": "ClinicalTrials.gov, sponsor or collaborator" }, { "key": "trials.gastricPh3", "label": "of which phase 3", "source": "same, phase filter" } ], "caveat": "Publication counts favour academic centres; trial counts favour sponsors. Read the two columns separately.", "rows": [ { "id": "pkuch", "name": "Peking University (incl. Peking University Cancer Hospital)", "country": "CN", "type": "center", "values": [ 779, 56, 2 ], "rank": 1 }, { "id": "fuscc", "name": "Fudan University (incl. Fudan University Shanghai Cancer Center)", "country": "CN", "type": "center", "values": [ 762, 39, 8 ], "rank": 2 }, { "id": "ncc-japan", "name": "National Cancer Center Japan", "country": "JP", "type": "center", "values": [ 609, 8, 1 ], "rank": 3 }, { "id": "snuh", "name": "Seoul National University (SNUH, Bundang, Boramae)", "country": "KR", "type": "center", "values": [ 523, 24, 2 ], "rank": 4 }, { "id": "yonsei", "name": "Yonsei University (Severance, Gangnam, Yongin)", "country": "KR", "type": "center", "values": [ 431, 49, 3 ], "rank": 5 }, { "id": "smc", "name": "Sungkyunkwan University (Samsung Medical Center, Kangbuk Samsung, Samsung Changwon)", "country": "KR", "type": "center", "values": [ 317, 24, 2 ], "rank": 6 }, { "id": "ncc-korea", "name": "National Cancer Center, Korea", "country": "KR", "type": "center", "values": [ 265, 17, 1 ], "rank": 7 }, { "id": "mdacc", "name": "The University of Texas MD Anderson Cancer Center", "country": "US", "type": "center", "values": [ 261, 23, 0 ], "rank": 8 }, { "id": "mskcc", "name": "Memorial Sloan Kettering Cancer Center", "country": "US", "type": "center", "values": [ 236, 8, 0 ], "rank": 9 }, { "id": "nci-us", "name": "U.S. National Cancer Institute", "country": "US", "type": "infrastructure", "values": [ 158, 79, 6 ], "rank": 10 }, { "id": "dfci", "name": "Dana-Farber Cancer Institute", "country": "US", "type": "center", "values": [ 84, 3, 0 ], "rank": 11 }, { "id": "nki", "name": "Netherlands Cancer Institute", "country": "NL", "type": "center", "values": [ 83, 5, 1 ], "rank": 12 }, { "id": "msd", "name": "Merck & Co. (MSD)", "country": "US", "type": "industry", "values": [ 36, 54, 10 ], "rank": 13 }, { "id": "gustave-roussy", "name": "Gustave Roussy", "country": "FR", "type": "center", "values": [ 33, 2, 0 ], "rank": 14 }, { "id": "broad", "name": "Broad Institute of MIT and Harvard", "country": "US", "type": "infrastructure", "values": [ 33, null, null ], "rank": 15 }, { "id": "astrazeneca", "name": "AstraZeneca", "country": "UK", "type": "industry", "values": [ 25, 39, 4 ], "rank": 16 }, { "id": "daiichi", "name": "Daiichi Sankyo", "country": "JP", "type": "industry", "values": [ 25, 17, 2 ], "rank": 17 }, { "id": "astellas", "name": "Astellas Pharma", "country": "JP", "type": "industry", "values": [ 25, 10, 3 ], "rank": 18 }, { "id": "lilly", "name": "Eli Lilly and Company", "country": "US", "type": "industry", "values": [ 22, 12, 2 ], "rank": 19 }, { "id": "roche", "name": "Roche (incl. Genentech)", "country": "CH", "type": "industry", "values": [ 15, 9, 1 ], "rank": 20 }, { "id": "pfizer", "name": "Pfizer", "country": "US", "type": "industry", "values": [ 7, 15, 0 ], "rank": 21 }, { "id": "novartis", "name": "Novartis", "country": "CH", "type": "industry", "values": [ 7, 9, 2 ], "rank": 22 }, { "id": "carsgen", "name": "CARsgen Therapeutics", "country": "CN", "type": "industry", "values": [ 6, 5, 0 ], "rank": 23 }, { "id": "sanger", "name": "Wellcome Sanger Institute", "country": "UK", "type": "infrastructure", "values": [ 5, null, null ], "rank": 24 }, { "id": "remegen", "name": "RemeGen", "country": "CN", "type": "industry", "values": [ 3, 9, 4 ], "rank": 25 }, { "id": "embl-ebi", "name": "EMBL's European Bioinformatics Institute (EMBL-EBI)", "country": "UK", "type": "infrastructure", "values": [ 1, null, null ], "rank": 26 } ], "notMeasured": [ { "id": "rcsb", "name": "RCSB Protein Data Bank", "country": "US", "type": "infrastructure", "values": [ 0, null, null ] }, { "id": "deepmind", "name": "Google DeepMind", "country": "UK", "type": "infrastructure", "values": [ 0, null, null ] }, { "id": "ipd", "name": "Institute for Protein Design, University of Washington", "country": "US", "type": "infrastructure", "values": [ 0, null, null ] }, { "id": "relay", "name": "Relay Therapeutics", "country": "US", "type": "industry", "values": [ 0, 0, 0 ] } ], "self": { "id": "riscon", "name": "RISCON Labs", "country": "KR", "type": "independent", "values": [ 0, 0, 0 ], "rank": null, "standing": "Not Assessed" }, "sensitivity": { "rule": "hospital name only for the university medical systems (the earlier expressions)", "rows": [ { "id": "ncc-japan", "name": "National Cancer Center Japan", "rank": 3, "altRank": 1, "narrowCount": null }, { "id": "pkuch", "name": "Peking University (incl. Peking University Cancer Hospital)", "rank": 1, "altRank": 2, "narrowCount": 474 }, { "id": "yonsei", "name": "Yonsei University (Severance, Gangnam, Yongin)", "rank": 5, "altRank": 3, "narrowCount": 426 }, { "id": "ncc-korea", "name": "National Cancer Center, Korea", "rank": 7, "altRank": 4, "narrowCount": null }, { "id": "mdacc", "name": "The University of Texas MD Anderson Cancer Center", "rank": 8, "altRank": 5, "narrowCount": null }, { "id": "fuscc", "name": "Fudan University (incl. Fudan University Shanghai Cancer Center)", "rank": 2, "altRank": 6, "narrowCount": 258 }, { "id": "smc", "name": "Sungkyunkwan University (Samsung Medical Center, Kangbuk Samsung, Samsung Changwon)", "rank": 6, "altRank": 7, "narrowCount": 246 }, { "id": "snuh", "name": "Seoul National University (SNUH, Bundang, Boramae)", "rank": 4, "altRank": 8, "narrowCount": 238 } ] } }, { "id": "RK-B", "name": "Breast Cancer Research", "applies": [ "center", "industry", "infrastructure" ], "indicators": [ { "key": "pubs.breast", "label": "Breast publications 2021–2025", "source": "PubMed, affiliation + topic query" }, { "key": "trials.breast", "label": "Breast trials started 2016–2025", "source": "ClinicalTrials.gov" }, { "key": "trials.breastPh3", "label": "of which phase 3", "source": "same, phase filter" } ], "caveat": "Same split as gastric.", "rows": [ { "id": "mdacc", "name": "The University of Texas MD Anderson Cancer Center", "country": "US", "type": "center", "values": [ 1881, 109, 3 ], "rank": 1 }, { "id": "mskcc", "name": "Memorial Sloan Kettering Cancer Center", "country": "US", "type": "center", "values": [ 1671, 83, 4 ], "rank": 2 }, { "id": "dfci", "name": "Dana-Farber Cancer Institute", "country": "US", "type": "center", "values": [ 1643, 107, 0 ], "rank": 3 }, { "id": "fuscc", "name": "Fudan University (incl. Fudan University Shanghai Cancer Center)", "country": "CN", "type": "center", "values": [ 1517, 178, 40 ], "rank": 4 }, { "id": "pkuch", "name": "Peking University (incl. Peking University Cancer Hospital)", "country": "CN", "type": "center", "values": [ 1145, 52, 4 ], "rank": 5 }, { "id": "snuh", "name": "Seoul National University (SNUH, Bundang, Boramae)", "country": "KR", "type": "center", "values": [ 907, 31, 4 ], "rank": 6 }, { "id": "nki", "name": "Netherlands Cancer Institute", "country": "NL", "type": "center", "values": [ 845, 30, 3 ], "rank": 7 }, { "id": "nci-us", "name": "U.S. National Cancer Institute", "country": "US", "type": "infrastructure", "values": [ 791, 475, 32 ], "rank": 8 }, { "id": "yonsei", "name": "Yonsei University (Severance, Gangnam, Yongin)", "country": "KR", "type": "center", "values": [ 727, 32, 1 ], "rank": 9 }, { "id": "smc", "name": "Sungkyunkwan University (Samsung Medical Center, Kangbuk Samsung, Samsung Changwon)", "country": "KR", "type": "center", "values": [ 713, 29, 1 ], "rank": 10 }, { "id": "gustave-roussy", "name": "Gustave Roussy", "country": "FR", "type": "center", "values": [ 689, 16, 2 ], "rank": 11 }, { "id": "ncc-japan", "name": "National Cancer Center Japan", "country": "JP", "type": "center", "values": [ 426, 1, 1 ], "rank": 12 }, { "id": "ncc-korea", "name": "National Cancer Center, Korea", "country": "KR", "type": "center", "values": [ 320, 9, 0 ], "rank": 13 }, { "id": "pfizer", "name": "Pfizer", "country": "US", "type": "industry", "values": [ 295, 139, 16 ], "rank": 14 }, { "id": "roche", "name": "Roche (incl. Genentech)", "country": "CH", "type": "industry", "values": [ 274, 97, 28 ], "rank": 15 }, { "id": "astrazeneca", "name": "AstraZeneca", "country": "UK", "type": "industry", "values": [ 266, 134, 32 ], "rank": 16 }, { "id": "broad", "name": "Broad Institute of MIT and Harvard", "country": "US", "type": "infrastructure", "values": [ 187, null, null ], "rank": 17 }, { "id": "novartis", "name": "Novartis", "country": "CH", "type": "industry", "values": [ 185, 89, 16 ], "rank": 18 }, { "id": "lilly", "name": "Eli Lilly and Company", "country": "US", "type": "industry", "values": [ 150, 58, 8 ], "rank": 19 }, { "id": "daiichi", "name": "Daiichi Sankyo", "country": "JP", "type": "industry", "values": [ 115, 53, 16 ], "rank": 20 }, { "id": "msd", "name": "Merck & Co. 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It does not measure patient benefit, and a sponsor with few but decisive trials ranks below a sponsor with many.", "rows": [ { "id": "roche", "name": "Roche (incl. Genentech)", "country": "CH", "type": "industry", "values": [ 16, 20, 9 ], "rank": 1 }, { "id": "astrazeneca", "name": "AstraZeneca", "country": "UK", "type": "industry", "values": [ 9, 24, 16 ], "rank": 2 }, { "id": "msd", "name": "Merck & Co. 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Eligibility criteria, assay and tumor site are recorded with each study; no universal cut-off is assumed, nor any equivalence between colon and rectal settings." }, { "id": "sub:B-HER2POS", "label": "HER2-positive", "kind": "subtype", "program": "breast", "def": "HER2 IHC 3+ or ISH-amplified (IHC 2+/ISH+), regardless of hormone-receptor status." }, { "id": "sub:B-HRPOS", "label": "HR-positive / HER2-negative", "kind": "subtype", "program": "breast", "def": "Oestrogen and/or progesterone receptor positive, HER2 not positive. Includes HER2-0, HER2-ultralow and HER2-low tumours." }, { "id": "sub:B-TNBC", "label": "Triple-negative", "kind": "subtype", "program": "breast", "def": "ER-negative, PR-negative and HER2-negative (NCI definition). Includes HER2-low and HER2-0 tumours." }, { "id": "sub:G-HER2", "label": "HER2-positive", "kind": "subtype", "program": "gastric", "def": "IHC 3+ or IHC 2+ with ISH/FISH amplification, scored with gastric-specific criteria." }, { "id": "sub:G-HER2NEG", "label": "HER2-negative", "kind": "subtype", "program": "gastric", "def": "Not HER2-positive by the gastric criteria." }, { "id": "sub:G-CLDN", "label": "CLDN18.2-positive", "kind": "subtype", "program": "gastric", "def": "Defined by IHC; the threshold differs by study (≥75% moderate-to-strong membranous staining in SPOTLIGHT; ≥2+ in ≥40% of cells in CT041-ST-01)." }, { "id": "sub:G-PDL1", "label": "PD-L1 CPS-defined", "kind": "subtype", "program": "gastric", "def": "Subsets defined by PD-L1 combined positive score cut-offs used in trials (≥1, ≥5). A biomarker subset, not a target." }, { "id": "sub:G-MSI", "label": "MSI-H / dMMR", "kind": "subtype", "program": "gastric", "def": "Microsatellite instability-high or mismatch-repair deficient; a genomic state used to select PD-1 blockade." }, { "id": "sub:G-TCGA", "label": "TCGA molecular subtypes", "kind": "subtype", "program": "gastric", "def": "EBV-positive, microsatellite unstable, genomically stable, chromosomally unstable (TCGA 2014). A research classification, not a treatment-selection rule." }, { "id": "tgt:ERBB2", "label": "HER2", "kind": "target", "evidenceCount": 74 }, { "id": "tgt:CLDN18.2", "label": "CLDN18.2", "kind": "target", "evidenceCount": 5 }, { "id": "tgt:ESR1", "label": "ERα", "kind": "target", "evidenceCount": 15 }, { "id": "tgt:PIK3CA", "label": "PI3Kα", "kind": "target", "evidenceCount": 6 }, { "id": "tgt:AKT", "label": "AKT", "kind": "target", "evidenceCount": 2 }, { "id": "tgt:CDK4/6", "label": "CDK4/6", "kind": "target", "evidenceCount": 25 }, { "id": "tgt:TACSTD2", "label": "TROP2", "kind": "target", "evidenceCount": 9 }, { "id": "tgt:PDCD1", "label": "PD-1", "kind": "target", "evidenceCount": 34 }, { "id": "tgt:CD274", "label": "PD-L1", "kind": "target", "evidenceCount": 12 }, { "id": "tgt:KDR", "label": "VEGFR2", "kind": "target", "evidenceCount": 8 }, { "id": "tgt:PARP1", "label": "PARP1/2", "kind": "target", "evidenceCount": 4 }, { "id": "tgt:FGFR2", "label": "FGFR2", "kind": "target", "evidenceCount": 4 }, { "id": "bm:BM-MSI-C", "label": "MSI-H / dMMR (colorectal)", "kind": "biomarker", "program": "colorectal", "kind2": "Selection biomarker (study-defined genomic state)" }, { "id": "bm:BM-HER2-G", "label": "HER2 status (gastric)", "kind": "biomarker", "program": "gastric", "kind2": "Target and selection biomarker" }, { "id": "bm:BM-HER2-B", "label": "HER2 status (breast)", "kind": "biomarker", "program": "breast", "kind2": "Target and selection biomarker" }, { "id": "bm:BM-HER2LOW-B", "label": "HER2-low / ultralow (breast)", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-HER2LOW-G", "label": "HER2-low (gastric)", "kind": "biomarker", "program": "gastric", "kind2": "Exploratory biomarker" }, { "id": "bm:BM-pERBB2", "label": "Plasma ERBB2 amplification", "kind": "biomarker", "program": "gastric", "kind2": "Exploratory biomarker" }, { "id": "bm:BM-HER2HET", "label": "HER2 heterogeneity (gastric)", "kind": "biomarker", "program": "gastric", "kind2": "Exploratory biomarker" }, { "id": "bm:BM-COAMP", "label": "Co-alterations with ERBB2", "kind": "biomarker", "program": "gxb", "kind2": "Hypothesis" }, { "id": "bm:BM-CLDN18", "label": "CLDN18.2 IHC", "kind": "biomarker", "program": "gastric", "kind2": "Target and selection biomarker" }, { "id": "bm:BM-PDL1-CPS", "label": "PD-L1 CPS (gastric)", "kind": "biomarker", "program": "gastric", "kind2": "Selection biomarker" }, { "id": "bm:BM-PDL1-TAP", "label": "PD-L1 TAP score", "kind": "biomarker", "program": "gastric", "kind2": "Selection biomarker" }, { "id": "bm:BM-PDL1-B", "label": "PD-L1 (TNBC)", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-MSI", "label": "MSI-H / dMMR", "kind": "biomarker", "program": "gastric", "kind2": "Selection biomarker (genomic state)" }, { "id": "bm:BM-EBV", "label": "EBV-positive gastric", "kind": "biomarker", "program": "gastric", "kind2": "Research classification" }, { "id": "bm:BM-ESR1", "label": "ESR1 mutation", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-PI3K", "label": "PIK3CA / AKT1 / PTEN alterations", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-gBRCA", "label": "Germline BRCA1/2", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-HR", "label": "ER / PR status", "kind": "biomarker", "program": "breast", "kind2": "Selection biomarker" }, { "id": "bm:BM-TROP2", "label": "TROP2 expression", "kind": "biomarker", "program": "breast", "kind2": "Target antigen, not a selection biomarker" }, { "id": "str:SD-ERBB2", "label": "ERBB2 structures", "kind": "structure", "target": "ERBB2" }, { "id": "str:SD-CLDN18", "label": "CLDN18 structures", "kind": "structure", "target": "CLDN18.2" }, { "id": "str:SD-ESR1", "label": "ESR1 structures", "kind": "structure", "target": "ESR1" }, { "id": "str:SD-PIK3CA", "label": "PIK3CA structures", "kind": "structure", "target": "PIK3CA" }, { "id": "ev:U-ToGA", "label": "ToGA", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-Hofmann08", "label": "Gastric HER2 scoring", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "literature", "kindOf": "method" }, { "id": "ev:U-GEAHER2", "label": "CAP/ASCP/ASCO GEA HER2 guideline", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "literature", "kindOf": "guideline" }, { "id": "ev:U-DG01", "label": "DESTINY-Gastric01", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DG02", "label": "DESTINY-Gastric02", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-DG04", "label": "DESTINY-Gastric04", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-GATSBY", "label": "GATSBY", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-JACOB", "label": "JACOB", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-LOGiC", "label": "LOGiC", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TyTAN", "label": "TyTAN", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-KN811", "label": "KEYNOTE-811", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-HERIZON", "label": "HERIZON-GEA-01", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-GASTHER3", "label": "GASTHER3", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-HER2loss16", "label": "HER2 loss after trastuzumab (2016)", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-Janjigian18", "label": "Esophagogastric genomic predictors", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-VIKTORY", "label": "VIKTORY", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-TCGASTAD", "label": "TCGA gastric", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-SPOTLIGHT", "label": "SPOTLIGHT", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-GLOW", "label": "GLOW", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CT041", "label": "Satri-cel CT041-ST-01", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CM649", "label": "CheckMate 649", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-KN859", "label": "KEYNOTE-859", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RAT305", "label": "RATIONALE-305", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-VESTIGE", "label": "VESTIGE (EORTC 1707)", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-KN061", "label": "KEYNOTE-061", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-KN062", "label": "KEYNOTE-062", "kind": "evidence", "program": "gastric", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RAINBOW", "label": "RAINBOW", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-REGARD", "label": "REGARD", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RAINFALL", "label": "RAINFALL", "kind": "evidence", "program": "gastric", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CLASSIC", "label": "CLASSIC", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-JAVG100", "label": "JAVELIN Gastric 100", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DPT02", "label": "DESTINY-PanTumor02", "kind": "evidence", "program": "expansion", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-CLEOPATRA", "label": "CLEOPATRA", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-EMILIA", "label": "EMILIA", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-EGF100151", "label": "Lapatinib + capecitabine (EGF100151)", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DB03", "label": "DESTINY-Breast03", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DB04", "label": "DESTINY-Breast04", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DB06", "label": "DESTINY-Breast06", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DB09", "label": "DESTINY-Breast09", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-HER2CLIMB", "label": "HER2CLIMB", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ASCOCAP23", "label": "ASCO–CAP HER2 testing update 2023", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "literature", "kindOf": "guideline" }, { "id": "ev:U-monarchE", "label": "monarchE", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-NATALEE", "label": "NATALEE", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-PALLAS", "label": "PALLAS", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-PENELOPEB", "label": "PENELOPE-B", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-SOLAR1", "label": "SOLAR-1", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CAP291", "label": "CAPItello-291", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-INAVO120", "label": "INAVO120", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RLY2608", "label": "RLY-2608", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-EMERALD", "label": "EMERALD", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-PADA1", "label": "PADA-1", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-SERENA6", "label": "SERENA-6", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-POSITIVE", "label": "POSITIVE (NCT02308085)", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-POEMS", "label": "POEMS/S0230 (goserelin for ovarian protection)", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-PROMISEGIM6", "label": "PROMISE-GIM6", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-STOCKHOLMHRT", "label": "Stockholm HRT after breast cancer trial", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-HABITS", "label": "HABITS", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-LIBERATE", "label": "Tibolone vs placebo in breast-cancer survivors with vasomotor symptoms (NCT00408863)", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-OASIS4", "label": "OASIS-4", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-NSABPP1", "label": "NSABP P-1 (Breast Cancer Prevention Trial), 7-year update", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-EMBER3", "label": "EMBER-3", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-VIKTORIA1", "label": "VIKTORIA-1 (PIK3CA wild-type)", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-VERITAC2", "label": "VERITAC-2", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TROPiCS02", "label": "TROPiCS-02", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TROPIONB01", "label": "TROPION-Breast01", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-Razavi18", "label": "Endocrine-resistant genomic landscape", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-Fanning16", "label": "ESR1 Y537S/D538G mechanism", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-KN522", "label": "KEYNOTE-522", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-IMP130", "label": "IMpassion130", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-IMP131", "label": "IMpassion131", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ASCENT", "label": "ASCENT", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-OlympiA", "label": "OlympiA", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TCGABRCA", "label": "TCGA breast", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-METABRIC", "label": "METABRIC", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-CPTACBRCA", "label": "CPTAC breast proteogenomics", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "genomics" }, { "id": "ev:U-AF2", "label": "AlphaFold 2", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "method" }, { "id": "ev:U-AFDB", "label": "AlphaFold Protein Structure Database", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-AF3", "label": "AlphaFold 3", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "method" }, { "id": "ev:U-AFServer", "label": "AlphaFold Server", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-RoseTTAFold", "label": "RoseTTAFold", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "method" }, { "id": "ev:U-RFdiffusion", "label": "RFdiffusion", "kind": "evidence", "program": "method", "result": "descriptive", "level": "literature", "kindOf": "method" }, { "id": "ev:U-HER2Fab", "label": "HER2 ECD + trastuzumab Fab (1N8Z)", "kind": "evidence", "program": "structure", "result": "descriptive", "level": "preclinical", "kindOf": "structure" }, { "id": "ev:U-HER2Pert", "label": "HER2 ECD + pertuzumab Fab (1S78)", "kind": "evidence", "program": "structure", "result": "descriptive", "level": "preclinical", "kindOf": "structure" }, { "id": "ev:U-ERago", "label": "ERα LBD agonist/antagonist (1ERE)", "kind": "evidence", "program": "structure", "result": "descriptive", "level": "preclinical", "kindOf": "structure" }, { "id": "ev:U-ERtam", "label": "ERα LBD + 4-hydroxytamoxifen (3ERT)", "kind": "evidence", "program": "structure", "result": "descriptive", "level": "preclinical", "kindOf": "structure" }, { "id": "ev:U-BYL719", "label": "Alpelisib discovery (4JPS)", "kind": "evidence", "program": "structure", "result": "descriptive", "level": "preclinical", "kindOf": "structure" }, { "id": "ev:U-cBio", "label": "cBioPortal", "kind": "evidence", "program": "data", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-GENIE", "label": "AACR Project GENIE", "kind": "evidence", "program": "data", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-DepMap", "label": "Cancer Dependency Map", "kind": "evidence", "program": "data", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-GDC", "label": "NCI Genomic Data Commons", "kind": "evidence", "program": "data", "result": "descriptive", "level": "literature", "kindOf": "resource" }, { "id": "ev:U-NCI-BREAST", "label": "NCI: Targeted therapy for breast cancer", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "literature", "kindOf": "reference-page" }, { "id": "ev:U-NCI-PDQ", "label": "NCI PDQ: Stomach cancer treatment (HP)", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "literature", "kindOf": "reference-page" }, { "id": "ev:U-A1", "label": "A1 · ERBB2 co-amplification, TCGA gastric vs breast", "kind": "evidence", "program": "gxb", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-A2", "label": "A2 · ESR1 and PIK3CA, primary vs metastatic", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-A3", "label": "A3 · CLDN18 isoform comparison", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-A5", "label": "A5 · Paired ESR1 detection in primary and metastatic breast specimens", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-DS8201pre16", "label": "DS-8201a functional preclinical profile", "kind": "evidence", "program": "gxb", "result": "positive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-ZOLpre24", "label": "Zolbetuximab functional gastric models", "kind": "evidence", "program": "gastric", "result": "positive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-AZD5363pre12", "label": "AZD5363 functional AKT pharmacology", "kind": "evidence", "program": "breast", "result": "mixed", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-PD0332991pre09", "label": "PD 0332991 functional breast cell-line study", "kind": "evidence", "program": "breast", "result": "mixed", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-SGpre15", "label": "IMMU-132 functional gastric xenograft evidence", "kind": "evidence", "program": "gastric", "result": "positive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-PD1Rupp22", "label": "PD-1 blockade in syngeneic TNBC models", "kind": "evidence", "program": "breast", "result": "positive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-PDL1Glyco16", "label": "PD-L1 glycosylation and immune suppression", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-VEGFR2Mashima21", "label": "VEGFR2 blockade and host VEGF-A feedback", "kind": "evidence", "program": "gastric", "result": "positive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-PARPRottenberg08", "label": "PARP inhibition in BRCA1-deficient mammary tumors", "kind": "evidence", "program": "breast", "result": "mixed", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-FGFR2Xie13", "label": "FGFR2-amplified gastric cancer dependency", "kind": "evidence", "program": "gastric", "result": "mixed", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-FLOT4", "label": "FLOT4 perioperative chemotherapy", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ctDNAYang20", "label": "Postoperative ctDNA recurrence cohort (Yang 2020)", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-ctDNAYuan23", "label": "Post-adjuvant ctDNA recurrence cohort (Yuan 2023)", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-KATHERINE", "label": "KATHERINE · long-term residual-disease follow-up", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-IMP030", "label": "ALEXANDRA/IMpassion030 · surgery-first adjuvant immunotherapy", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-cTRAKTN", "label": "c-TRAK TN · ctDNA surveillance and triggered intervention", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-DYNAMIC", "label": "DYNAMIC · ctDNA-guided stage II colon adjuvant strategy", "kind": "evidence", "program": "colorectal", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-NICHE2", "label": "NICHE-2 · neoadjuvant dual checkpoint blockade", "kind": "evidence", "program": "colorectal", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-DOSTrectal", "label": "Dostarlimab · dMMR rectal organ preservation", "kind": "evidence", "program": "colorectal", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-KN177", "label": "KEYNOTE-177 · final analysis and long-term follow-up", "kind": "evidence", "program": "colorectal", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-SELECT", "label": "SELECT (lenvatinib)", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-DECISION", "label": "DECISION", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-COSMIC311", "label": "COSMIC-311", "kind": "evidence", "program": "thyroid", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-LIBRETTO531", "label": "LIBRETTO-531", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-LIBRETTO001", "label": "LIBRETTO-001 (thyroid cohorts)", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-T-ROAR", "label": "ROAR (anaplastic thyroid cohort)", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-KoreaThyScreen16", "label": "Korean thyroid screening · regional incidence and mortality", "kind": "evidence", "program": "thyroid", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-HashimotoPTC17", "label": "Hashimoto thyroiditis and papillary cancer · observational meta-analysis", "kind": "evidence", 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"KEYNOTE-585 · perioperative pembrolizumab", "kind": "evidence", "program": "gastric", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ATT5", "label": "ATTRACTION-5 · postoperative nivolumab", "kind": "evidence", "program": "gastric", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CREATEX", "label": "CREATE-X · HER2-negative residual disease", "kind": "evidence", "program": "breast", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-EA1131", "label": "EA1131 · platinum versus capecitabine", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ACTSGC", "label": "ACTS-GC · postoperative S-1 after D2 gastrectomy", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-ARTIST2", "label": "ARTIST 2 · postoperative chemotherapy and radiation", "kind": "evidence", "program": "gastric", 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"rct" }, { "id": "ev:U-RAPIDO", "label": "RAPIDO · early treatment failure and later local recurrence", "kind": "evidence", "program": "colorectal", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RESOLVE", "label": "RESOLVE · corrected comparisons and final survival follow-up", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TAGS", "label": "TAGS · later-line trifluridine/tipiracil and quality of life", "kind": "evidence", "program": "gastric", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-RxPONDER", "label": "RxPONDER", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TAILORx", "label": "TAILORx", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-MINDACT", "label": "MINDACT", "kind": "evidence", "program": "breast", "result": "mixed", 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"clinical", "kindOf": "single-arm" }, { "id": "ev:U-AtezoTRIBE", "label": "AtezoTRIBE · atezolizumab added to first-line FOLFOXIRI and bevacizumab", "kind": "evidence", "program": "colorectal", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-LENVA211", "label": "Study 211 · lenvatinib starting dose 18 mg versus 24 mg in radioiodine-refractory thyroid cancer", "kind": "evidence", "program": "thyroid", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-Donafenib23", "label": "Donafenib in progressive radioiodine-refractory differentiated thyroid cancer · Chinese phase III trial", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-ALTER01031", "label": "ALTER 01031 · anlotinib in advanced medullary thyroid carcinoma", "kind": "evidence", "program": "thyroid", "result": "positive", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-A8", "label": "A8 · BRAF V600E by MSI status in three colorectal cancer cohorts", "kind": "evidence", "program": "colorectal", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-TDXdILA26", "label": "Baseline lung abnormalities and T-DXd-associated ILD: retrospective risk association", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-EosinophilHR26", "label": "Eosinophils, recurrence and CDK4/6 benefit: biomarker association requiring interaction audit", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-ACTOrganoid26", "label": "AC-T component heterogeneity and a constructed organoid response score", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-QBS72S26", "label": "QBS72S: separate leptomeningeal observations and parenchymal response cohort", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-A9", "label": "A9 · BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer, MSK-IMPACT 50K", "kind": "evidence", "program": "thyroid", "result": "descriptive", "level": "computational", "kindOf": "analysis" }, { "id": "ev:U-PD1MaintenanceCRC26", "label": "Observation or maintenance after clinical complete response: selected non-operative colorectal cohort", "kind": "evidence", "program": "colorectal", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-FABP4Peritoneal26", "label": "Adipocyte-linked ferroptosis resistance in gastric peritoneal metastasis", "kind": "evidence", "program": "gastric", "result": "descriptive", "level": "preclinical", "kindOf": "preclinical" }, { "id": "ev:U-HER2ResidualDiscord26", "label": "HER2 discordance after neoadjuvant therapy: residual-disease selection and measurement", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-INTEGRAL26", "label": "INTEGRAL: early termination of intratumoral IL-12 combination in anthracycline-refractory TNBC", "kind": "evidence", "program": "breast", "result": "negative", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-FIRE3", "label": "FIRE-3 · FOLFIRI with cetuximab or bevacizumab as first-line treatment", "kind": "evidence", "program": "colorectal", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CALGB80405", "label": "CALGB/SWOG 80405 · cetuximab or bevacizumab with first-line chemotherapy", "kind": "evidence", "program": "colorectal", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-TRIPLETE", "label": "TRIPLETE · mFOLFOXIRI versus modified FOLFOX with panitumumab", "kind": "evidence", "program": "colorectal", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-JCOG0603", "label": "JCOG0603 · hepatectomy with or without adjuvant mFOLFOX6 for liver-only metastases", "kind": "evidence", "program": "colorectal", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-T-DABTHY", "label": "Dabrafenib versus dabrafenib plus trametinib in BRAF-mutated radioiodine-refractory thyroid cancer", "kind": "evidence", "program": "thyroid", "result": "negative", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-NabDDHR26", "label": "Dose-dense nab-paclitaxel versus docetaxel in HR-positive early breast cancer", "kind": "evidence", "program": "breast", "result": "mixed", "level": "clinical", "kindOf": "rct" }, { "id": "ev:U-CRPMctDNA26", "label": "Perioperative ctDNA after cytoreduction for colorectal peritoneal metastases", "kind": "evidence", "program": "colorectal", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-HER2CR26", "label": "HER2-CR: residual ctDNA in durable responders with metastatic breast cancer", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "observational" }, { "id": "ev:U-CA2098M4", "label": "CA209-8M4: nivolumab plus total neoadjuvant therapy for rectal cancer", "kind": "evidence", "program": "colorectal", "result": "mixed", "level": "clinical", "kindOf": "single-arm" }, { "id": "ev:U-UCI1467", "label": "UCI 14-67: first posted neoadjuvant results by HER2 status", "kind": "evidence", "program": "breast", "result": "descriptive", "level": "clinical", "kindOf": "registry" }, { "id": "qp:QP-01", "label": "유방암 HER2 근거를 위암에 어디까지 쓸 것인가", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-02", "label": "구조 신뢰도만으로 표적 순위를 정하는가", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-03", "label": "치료 반응 비교 전에 환자군 차이부터 맞춤", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-04", "label": "상충 결과가 나왔을 때 가설을 보류함", "kind": "pair", "program": "breast" }, { "id": "qp:QP-05", "label": "새 분석과 재현 중 무엇을 먼저 할 것인가", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-06", "label": "2차 치료 비교 전에 HER2를 다시 재는가", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-07", "label": "판정 기준이 다른 두 대상군을 합치지 않음", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-08", "label": "진행 전 교체의 이득을 무엇으로 셀 것인가", "kind": "pair", "program": "breast" }, { "id": "qp:QP-09", "label": "PD-L1 점수는 서로 바꿔 쓸 수 있는가", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-10", "label": "HER2 저발현은 아형이 아니라 발현 수준임", "kind": "pair", "program": "breast" }, { "id": "qp:QP-11", "label": "ADC를 이어 쓴 결과를 무엇으로 추정하는가", "kind": "pair", "program": "breast" }, { "id": "qp:QP-12", "label": "예측 서버 출력을 자동 검색에 연결함", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-13", "label": "동형을 가리지 않은 예측 모델은 쓰지 않음", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-14", "label": "재발과 전이를 반응 연구와 떼어 관리하는가", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-15", "label": "접합체의 작용과 표적 의존성을 구별함", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-16", "label": "항체 기능으로 동형 판별을 대신하지 않음", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-17", "label": "억제제 감수성은 분자 맥락을 붙여 읽는다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-18", "label": "면역 차단의 효과와 선별 점수를 나눔", "kind": "pair", "program": "breast" }, { "id": "qp:QP-19", "label": "종양 축소만으로 작용 위치를 단정하는가", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-20", "label": "수술 전후의 성적은 맥락을 맞춰 읽음", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-21", "label": "재발 예측과 치료 이득을 따로 판정한다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-22", "label": "혈액 신호가 개입의 기회를 보장하는가", "kind": "pair", "program": "breast" }, { "id": "qp:QP-23", "label": "완전반응 뒤에도 완치는 따로 확인함", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-24", "label": "암종을 옮긴 잔존 신호의 유용성은 보류", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-25", "label": "늘어난 진단과 검진의 이득은 별개", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-26", "label": "갑상선염과 암의 동반에서 인과를 보류", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-27", "label": "반응률은 비교 시험의 결론을 대신 못함", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-28", "label": "잔존암의 표적 변화는 약효 증거와 별개", "kind": "pair", "program": "breast" }, { "id": "qp:QP-29", "label": "진행 억제와 생존 개선을 따로 판정", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-30", "label": "장기 추적에 맞춰 생존 판단을 고침", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-31", "label": "수술 전후 병용의 기여는 분리 못함", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-32", "label": "잔존암 약효와 폐 위해를 함께 읽음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-33", "label": "선별된 진행성 병용 결과의 적용 범위", "kind": "pair", "program": "breast" }, { "id": "qp:QP-34", "label": "유지치료의 진행 지연을 재발 예방과 구분", "kind": "pair", "program": "breast" }, { "id": "qp:QP-35", "label": "진행 뒤 약제 유지와 교체는 별개다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-36", "label": "표적이 같아도 수술 뒤 조건은 다르다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-37", "label": "치료 축소는 무엇을 줄였는지부터 확인", "kind": "pair", "program": "breast" }, { "id": "qp:QP-38", "label": "직장암 전략의 강화와 생략을 구분함", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-39", "label": "생존 연장과 삶의 질은 따로 평가한다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-40", "label": "재발 위험 점수와 항암 이득은 다르다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-41", "label": "고발현 하위군만으로 성공을 정하지 않음", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-42", "label": "수술 뒤 면역치료 생략은 아직 미결", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-43", "label": "변이군의 진행 지연과 약제 순위는 별개", "kind": "pair", "program": "breast" }, { "id": "qp:QP-44", "label": "혈액 신호가 없어도 남는 직장암 절제 판단", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-45", "label": "핵으로 옮겨간 단백질과 내성 가설의 거리", "kind": "pair", "program": "breast" }, { "id": "qp:QP-46", "label": "간 전이 절제 후 조직검사로 읽는 재발 위험", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-47", "label": "손상 소기관 청소가 항암제 내성을 돕는 조건", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-48", "label": "소엽암의 아형별 위험 차이는 아직 미결", "kind": "pair", "program": "breast" }, { "id": "qp:QP-49", "label": "증식 지표의 변화와 수술 선택은 별개다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-50", "label": "면역항암 이득은 검사 점수 구간에 한정한다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-51", "label": "대장암 HER2 표적 반응은 대조 없이 못 정함", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-52", "label": "같은 계열 약의 생존 성적을 서로 빌리지 않음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-53", "label": "갑상선염이 암을 부르는지 막는지는 미정", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-54", "label": "암으로 가지 않는 조건은 아직 정해지지 않음", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-55", "label": "호르몬 수치 조절과 종양 예방은 다른 문제", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-56", "label": "어린 환자의 결절은 성인 자료로 못 읽음", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-57", "label": "증상 없는 환자의 정기 초음파 이득은 미확인", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-58", "label": "추적 자료의 서로 다른 발생 비율은 합치지 않음", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-59", "label": "직장암 수술 보류의 안전성은 무작위 비교가 없다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-60", "label": "영상 반응으로 항암을 줄인 전략의 3년 성적", "kind": "pair", "program": "breast" }, { "id": "qp:QP-61", "label": "보조 퍼투주맙의 생존 이득은 아직 확정 전", "kind": "pair", "program": "breast" }, { "id": "qp:QP-62", "label": "같은 검사법에서도 위암 공동증폭이 더 잦았다", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-63", "label": "dMMR 결장암은 수술 전 항암 효과가 작게 보고됨", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-64", "label": "호르몬 양성 조기 유방암의 면역치료는 병리 결과뿐", "kind": "pair", "program": "breast" }, { "id": "qp:QP-65", "label": "화학요법을 뺀 두 방식은 결과가 서로 달랐다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-66", "label": "위암 병리 반응 상승과 재발 감소는 따로 본다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-67", "label": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-68", "label": "식도 접합부 보조 면역치료는 위암 근거가 아니다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-69", "label": "혈액 검사의 앞선 경고와 치료 이득은 별개", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-70", "label": "HER2 양성 병용의 재발 감소는 미확인", "kind": "pair", "program": "breast" }, { "id": "qp:QP-71", "label": "관찰 비교의 시간 조건부터 검토함", "kind": "pair", "program": "breast" }, { "id": "qp:QP-72", "label": "낮은 점수의 해석은 림프절 범위에 달린다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-73", "label": "복구 경로가 같아도 내성 조건은 다르다", "kind": "pair", "program": "gxb" }, { "id": "qp:QP-74", "label": "같은 유전자군도 억제 방향은 갈릴 수 있다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-75", "label": "GDSC 예측과 치료 반응의 검증은 다르다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-76", "label": "누적 간 위해는 보조·전이 치료를 나눠 읽음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-77", "label": "항체에 따라 점상 염색의 해석이 달라짐", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-78", "label": "낮은 수용체 발현군의 생존 연관을 따져 봄", "kind": "pair", "program": "breast" }, { "id": "qp:QP-79", "label": "엑손 조절과 환자 내성 극복은 분리함", "kind": "pair", "program": "breast" }, { "id": "qp:QP-80", "label": "수질암 두 시험의 위험비는 나란히 못 놓음", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-81", "label": "지켜본 저위험 유두암의 결과는 범위가 좁다", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-82", "label": "선택적 RET 억제제끼리의 우열은 비교가 없다", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-83", "label": "KRAS G12C 병용 효과는 고용량에서만 확인", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-84", "label": "후기 치료의 생존 이득은 크기를 함께 적는다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-85", "label": "보조 항암 기간 단축은 요법에 따라 갈린다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-86", "label": "BRAF 변이 일차 치료의 생존은 중간 분석 단계", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-87", "label": "dMMR 3기 보조 면역항암의 이득은 재발 지표까지", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-88", "label": "한 계열 세 약의 수명 연장 성적이 엇갈렸다", "kind": "pair", "program": "breast" }, { "id": "qp:QP-89", "label": "접합부암 수술 전 요법 비교는 시대가 어긋난다", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-90", "label": "진행만 늦춘 HER2 추가 약은 수명 이득 미정", "kind": "pair", "program": "breast" }, { "id": "qp:QP-91", "label": "요오드 생략의 비열등성은 5년 지표까지 봄", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-92", "label": "관찰 코호트의 종양 증가 비율은 기준이 다르다", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-94", "label": "같은 예측식도 사건에 따라 성능이 갈림", "kind": "pair", "program": "breast" }, { "id": "qp:QP-95", "label": "위암의 락틸화 차단은 세포·동물 근거임", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-96", "label": "효소의 재상승과 치료 선택 기준을 구분함", "kind": "pair", "program": "breast" }, { "id": "qp:QP-93", "label": "병리 판별력은 치료 성과와 따로 평가함", "kind": "pair", "program": "breast" }, { "id": "qp:QP-97", "label": "전이의 변이 시점과 재발 차단은 별개", "kind": "pair", "program": "breast" }, { "id": "qp:QP-98", "label": "내성 병용의 음성 결과와 위해를 함께 읽음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-99", "label": "변이별 투약 지속기간은 비교 약효와 다름", "kind": "pair", "program": "breast" }, { "id": "qp:QP-100", "label": "재발 상태별 예후를 보조치료 효과와 구별함", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-101", "label": "내성의 공간 신호와 병용 검증은 별개", "kind": "pair", "program": "breast" }, { "id": "qp:QP-102", "label": "장기 면역치료 추적과 수술 생략의 간극", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-103", "label": "미생물 제제의 반응 기여도는 아직 미정", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-104", "label": "잠재 재발 모형의 설명과 실측 사이", "kind": "pair", "program": "breast" }, { "id": "qp:QP-105", "label": "뇌 도달 약제의 병용에서도 멈춘 반응", "kind": "pair", "program": "breast" }, { "id": "qp:QP-106", "label": "방사선 분할 단축을 지지하는 범위", "kind": "pair", "program": "breast" }, { "id": "qp:QP-107", "label": "긴 추적이 남겨도 해결되지 않는 비교", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-108", "label": "PI3K 변이 대장암의 아스피린 이득은 재발까지", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-109", "label": "운동 프로그램의 생존 연장은 한 시험의 결과", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-110", "label": "pMMR 대장암 면역 병용은 시험마다 엇갈린다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-111", "label": "렌바티닙 시작 용량을 낮추면 반응이 줄었다", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-112", "label": "중국 시험의 표적 억제제 결과는 대상 안에서", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-113", "label": "미세한 폐 소견과 약제 위해의 연결", "kind": "pair", "program": "breast" }, { "id": "qp:QP-114", "label": "호산구의 재발 연관성과 치료 선택 사이", "kind": "pair", "program": "breast" }, { "id": "qp:QP-115", "label": "배양 반응 점수를 환자 확률로 옮기지 않음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-116", "label": "실질 뇌전이와 연수막 신호를 나눠 읽음", "kind": "pair", "program": "breast" }, { "id": "qp:QP-117", "label": "완전반응 뒤 유지 치료와 관찰의 간격", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-118", "label": "복막 전이의 지방 이용을 끊는 가설", "kind": "pair", "program": "gastric" }, { "id": "qp:QP-119", "label": "잔존 병변의 HER2 불일치를 읽는 범위", "kind": "pair", "program": "breast" }, { "id": "qp:QP-120", "label": "국소 면역 자극의 중단을 기록하는 기준", "kind": "pair", "program": "breast" }, { "id": "qp:QP-121", "label": "수술을 포함한 무재발과 완치의 경계", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-122", "label": "일차 항EGFR 항체의 생존 이득은 시험마다 다르다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-123", "label": "강화 요법이 늘린 지표와 생존은 따로 본다", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-124", "label": "분화암에서 MEK 억제제 추가 이득은 미확인", "kind": "pair", "program": "thyroid" }, { "id": "qp:QP-130", "label": "잔존 종양 부담 지표가 보여주는 범위", "kind": "pair", "program": "breast" }, { "id": "qp:QP-131", "label": "복막 전이의 잔존 신호를 읽는 조건", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-132", "label": "오래 반응한 유방암에서 음성 검사의 범위", "kind": "pair", "program": "breast" }, { "id": "qp:QP-133", "label": "수술 병리와 비수술 추적을 합친 반응률", "kind": "pair", "program": "colorectal" }, { "id": "qp:QP-134", "label": "허투에 따라 나뉜 치료군의 비교 한계", "kind": "pair", "program": "breast" }, { "id": "an:A1", "label": "A1 ERBB2 amplification and co-amplification", "kind": "analysis" }, { "id": "an:A2", "label": "A2 ESR1 and PIK3CA mutations", "kind": "analysis" }, { "id": "an:A3", "label": "A3 CLDN18 isoform A1 vs A2 sequence comparison", "kind": "analysis" }, { "id": "an:A5", "label": "A5 Paired ESR1 detection in primary and metastatic breast specimens", "kind": "analysis" }, { "id": "an:A6", "label": "A6 BRAF V600E frequency by recorded lymphocytic thyroiditis in TCGA papillary thyroid cancer", "kind": "analysis" }, { "id": "an:A7", "label": "A7 ERBB2 amplification by RAS/BRAF status in MSK metastatic colorectal cancer", "kind": "analysis" }, { "id": "an:A8", "label": "A8 BRAF V600E by MSI status in three colorectal cancer cohorts", "kind": "analysis" }, { "id": "an:A9", "label": "A9 BRAF V600E in papillary versus other follicular-cell-derived thyroid cancer", "kind": "analysis" } ], "edges": [ { "a": "prog:colorectal", "b": "sub:C-MSI", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:breast", "b": "sub:B-HER2POS", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:breast", "b": "sub:B-HRPOS", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:breast", "b": "sub:B-TNBC", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-HER2", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-HER2NEG", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-CLDN", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-PDL1", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-MSI", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "prog:gastric", "b": "sub:G-TCGA", "rel": "programme contains subtype", "src": "curated: entities.subtypes" }, { "a": "tgt:ERBB2", "b": "ev:U-ToGA", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DG01", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DG04", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-KN811", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-HERIZON", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-GATSBY", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-JACOB", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-LOGiC", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-TyTAN", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-CLEOPATRA", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-EMILIA", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DB03", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DB04", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DB06", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-DB09", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2CLIMB", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ERBB2", "b": "ev:U-NCI-BREAST", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "bm:BM-HER2-G", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-HER2-B", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-HER2LOW-B", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-HER2LOW-G", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-pERBB2", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-HER2HET", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-COAMP", "b": "tgt:ERBB2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:ERBB2", "b": "str:SD-ERBB2", "rel": "structure dossier for this target", "src": "curated: target.structure" }, { "a": "tgt:ERBB2", "b": "sub:G-HER2", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:ERBB2", "b": "sub:G-PDL1", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:ERBB2", "b": "sub:B-HER2POS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:ERBB2", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:CLDN18.2", "b": "ev:U-SPOTLIGHT", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:CLDN18.2", "b": "ev:U-GLOW", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:CLDN18.2", "b": "ev:U-CT041", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:CLDN18.2", "b": "ev:U-NCI-PDQ", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "bm:BM-CLDN18", "b": "tgt:CLDN18.2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:CLDN18.2", "b": "str:SD-CLDN18", "rel": "structure dossier for this target", "src": "curated: target.structure" }, { "a": "tgt:CLDN18.2", "b": "sub:G-CLDN", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:ESR1", "b": "ev:U-EMERALD", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ESR1", "b": "ev:U-EMBER3", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ESR1", "b": "ev:U-VERITAC2", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ESR1", "b": "ev:U-PADA1", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:ESR1", "b": "ev:U-SERENA6", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "bm:BM-ESR1", "b": "tgt:ESR1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-HR", "b": "tgt:ESR1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:ESR1", "b": "str:SD-ESR1", "rel": "structure dossier for this target", "src": "curated: target.structure" }, { "a": "tgt:ESR1", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PIK3CA", "b": "ev:U-SOLAR1", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PIK3CA", "b": "ev:U-INAVO120", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PIK3CA", "b": "ev:U-RLY2608", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PIK3CA", "b": "ev:U-TCGASTAD", "rel": "evidence in gastric: Biology only", "src": "curated: target.cancers" }, { "a": "bm:BM-PI3K", "b": "tgt:PIK3CA", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:PIK3CA", "b": "str:SD-PIK3CA", "rel": "structure dossier for this target", "src": "curated: target.structure" }, { "a": "tgt:PIK3CA", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PIK3CA", "b": "sub:G-TCGA", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:AKT", "b": "ev:U-CAP291", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:AKT", "b": "ev:U-NCI-BREAST", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "bm:BM-PI3K", "b": "tgt:AKT", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:AKT", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:CDK4/6", "b": "ev:U-monarchE", "rel": "evidence in breast: Established target (advanced); conflicting (adjuvant)", "src": "curated: target.cancers" }, { "a": "tgt:CDK4/6", "b": "ev:U-NATALEE", "rel": "evidence in breast: Established target (advanced); conflicting (adjuvant)", "src": "curated: target.cancers" }, { "a": "tgt:CDK4/6", "b": "ev:U-PALLAS", "rel": "evidence in breast: Established target (advanced); conflicting (adjuvant)", "src": "curated: target.cancers" }, { "a": "tgt:CDK4/6", "b": "ev:U-PENELOPEB", "rel": "evidence in breast: Established target (advanced); conflicting (adjuvant)", "src": "curated: target.cancers" }, { "a": "tgt:CDK4/6", "b": "ev:U-NCI-BREAST", "rel": "evidence in breast: Established target (advanced); conflicting (adjuvant)", "src": "curated: target.cancers" }, { "a": "bm:BM-HR", "b": "tgt:CDK4/6", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:CDK4/6", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:TACSTD2", "b": "ev:U-ASCENT", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:TACSTD2", "b": "ev:U-TROPiCS02", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:TACSTD2", "b": "ev:U-TROPIONB01", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:TACSTD2", "b": "ev:U-ASCENT04", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:TACSTD2", "b": "ev:U-ASCENT03", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "tgt:TACSTD2", "b": "ev:U-TROPIONB02", "rel": "evidence in breast: Established target", "src": "curated: target.cancers" }, { "a": "bm:BM-TROP2", "b": "tgt:TACSTD2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:TACSTD2", "b": "sub:B-TNBC", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:TACSTD2", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PDCD1", "b": "ev:U-CM649", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-KN859", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-RAT305", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-KN061", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-KN062", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-KN811", "rel": "evidence in gastric: Established target", "src": "curated: target.cancers" }, { "a": "tgt:PDCD1", "b": "ev:U-KN522", "rel": "evidence in breast: Established target (TNBC)", "src": "curated: target.cancers" }, { "a": "bm:BM-PDL1-CPS", "b": "tgt:PDCD1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-PDL1-TAP", "b": "tgt:PDCD1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-MSI", "b": "tgt:PDCD1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-EBV", "b": "tgt:PDCD1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:PDCD1", "b": "sub:G-PDL1", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PDCD1", "b": "sub:G-HER2NEG", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PDCD1", "b": "sub:G-HER2", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PDCD1", "b": "sub:B-TNBC", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:CD274", "b": "ev:U-IMP130", "rel": "evidence in breast: Conflicting", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-IMP131", "rel": "evidence in breast: Conflicting", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-IMP030", "rel": "evidence in breast: Conflicting", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-CM649", "rel": "evidence in gastric: Mixed", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-RAT305", "rel": "evidence in gastric: Mixed", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-MATTERHORN", "rel": "evidence in gastric: Mixed", "src": "curated: target.cancers" }, { "a": "tgt:CD274", "b": "ev:U-JAVG100", "rel": "evidence in gastric: Mixed", "src": "curated: target.cancers" }, { "a": "bm:BM-PDL1-B", "b": "tgt:CD274", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "bm:BM-PDL1-CPS", "b": "tgt:CD274", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:CD274", "b": "sub:B-TNBC", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:CD274", "b": "sub:G-PDL1", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:CD274", "b": "sub:G-HER2NEG", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:KDR", "b": "ev:U-RAINBOW", "rel": "evidence in gastric: Established (later lines)", "src": "curated: target.cancers" }, { "a": "tgt:KDR", "b": "ev:U-REGARD", "rel": "evidence in gastric: Established (later lines)", "src": "curated: target.cancers" }, { "a": "tgt:KDR", "b": "ev:U-RAINFALL", "rel": "evidence in gastric: Established (later lines)", "src": "curated: target.cancers" }, { "a": "tgt:KDR", "b": "ev:U-NCI-PDQ", "rel": "evidence in gastric: Established (later lines)", "src": "curated: target.cancers" }, { "a": "tgt:KDR", "b": "ev:U-RINDBeRG", "rel": "evidence in gastric: Established (later lines)", "src": "curated: target.cancers" }, { "a": "tgt:PARP1", "b": "ev:U-OlympiA", "rel": "evidence in breast: Established (BRCA-mutated)", "src": "curated: target.cancers" }, { "a": "tgt:PARP1", "b": "ev:U-NCI-BREAST", "rel": "evidence in breast: Established (BRCA-mutated)", "src": "curated: target.cancers" }, { "a": "tgt:PARP1", "b": "ev:U-EMBRACA", "rel": "evidence in breast: Established (BRCA-mutated)", "src": "curated: target.cancers" }, { "a": "tgt:PARP1", "b": "ev:U-OlympiAD", "rel": "evidence in breast: Established (BRCA-mutated)", "src": "curated: target.cancers" }, { "a": "bm:BM-gBRCA", "b": "tgt:PARP1", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:PARP1", "b": "sub:B-HRPOS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:PARP1", "b": "sub:B-TNBC", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:FGFR2", "b": "ev:U-A1", "rel": "evidence in gastric: Candidate", "src": "curated: target.cancers" }, { "a": "tgt:FGFR2", "b": "ev:U-FIGHT", "rel": "evidence in gastric: Candidate", "src": "curated: target.cancers" }, { "a": "tgt:FGFR2", "b": "ev:U-FORT101", "rel": "evidence in gastric: Candidate", "src": "curated: target.cancers" }, { "a": "bm:BM-COAMP", "b": "tgt:FGFR2", "rel": "biomarker selects for this target", "src": "curated: biomarker.selects" }, { "a": "tgt:FGFR2", "b": "sub:G-HER2", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "tgt:FGFR2", "b": "sub:B-HER2POS", "rel": "target studied in this subtype", "src": "derived: units of this target carry this subtype" }, { "a": "prog:gastric", "b": "ev:U-ToGA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-ToGA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-Hofmann08", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-Hofmann08", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-GEAHER2", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-GEAHER2", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-DG01", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-DG01", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-HER2LOW-G", "b": "ev:U-DG01", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-pERBB2", "b": "ev:U-DG01", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-DG02", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-DG02", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-DG02", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-DG04", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-DG04", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-GATSBY", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-GATSBY", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-JACOB", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-LOGiC", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-TyTAN", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-KN811", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-G", "b": "ev:U-KN811", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-KN811", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-HERIZON", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-HERIZON", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-HERIZON", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-GASTHER3", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-GASTHER3", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-GASTHER3", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-HER2HET", "b": "ev:U-GASTHER3", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-HER2loss16", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2loss16", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-HER2loss16", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-Janjigian18", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-Janjigian18", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-Janjigian18", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-VIKTORY", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-TCGASTAD", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-MSI", "b": "ev:U-TCGASTAD", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-EBV", "b": "ev:U-TCGASTAD", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-SPOTLIGHT", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-CLDN18", "b": "ev:U-SPOTLIGHT", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-GLOW", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-CLDN18", "b": "ev:U-GLOW", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-CT041", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-CLDN18", "b": "ev:U-CT041", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-CM649", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-CM649", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-KN859", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-KN859", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-RAT305", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PDL1-TAP", "b": "ev:U-RAT305", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-VESTIGE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-VESTIGE", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:gastric", "b": "ev:U-KN061", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-KN061", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-KN062", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-KN062", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-RAINBOW", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-REGARD", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-RAINFALL", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-CLASSIC", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-JAVG100", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:expansion", "b": "ev:U-DPT02", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-DPT02", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-CLEOPATRA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-CLEOPATRA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-EMILIA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-EMILIA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-EGF100151", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-EGF100151", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-DB03", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-DB03", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-DB04", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2LOW-B", "b": "ev:U-DB04", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-DB06", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2LOW-B", "b": "ev:U-DB06", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-DB09", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-DB09", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-HER2CLIMB", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-HER2CLIMB", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-ASCOCAP23", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HER2-B", "b": "ev:U-ASCOCAP23", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-HER2LOW-B", "b": "ev:U-ASCOCAP23", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-monarchE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-NATALEE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-PALLAS", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-PENELOPEB", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-SOLAR1", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PI3K", "b": "ev:U-SOLAR1", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CAP291", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-PI3K", "b": "ev:U-CAP291", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-INAVO120", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-INAVO120", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-PI3K", "b": "ev:U-INAVO120", "rel": "unit records this biomarker", "src": 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"evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-MSI-C", "b": "ev:U-FOxTROT", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:colorectal", "b": "ev:U-CM142", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-CM142", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-MSI-C", "b": "ev:U-CM142", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-PHERGain", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-PHERGain", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-PHERGain", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-APHINITY", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-APHINITY", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-APHINITY", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-PALOMA3", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-PALOMA3", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-PALOMA3", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-ORIENT16", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-ORIENT16", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-ORIENT16", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-ARMANI", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:KDR", "b": "ev:U-ARMANI", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:gastric", "b": "ev:U-CCNE1Lee15", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-CCNE1Lee15", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-CCNE1Lee15", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CyclinEScaltriti11", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-CyclinEScaltriti11", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-CyclinEScaltriti11", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-AMNESIA18", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-AMNESIA18", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-AMNESIA18", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-CCNE1Rustgi24", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-CCNE1Rustgi24", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-CCNE1Rustgi24", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-CCNE1TDXd24", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-CCNE1TDXd24", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-CCNE1TDXd24", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-HER2GCKwon23", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2GCKwon23", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-HER2GCKwon23", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-OncogeneDominance26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-OncogeneDominance26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-OncogeneDominance26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CyclinELuhtala16", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-CyclinELuhtala16", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-CyclinELuhtala16", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-SecondaryEventsKim14", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-SecondaryEventsKim14", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-COAMP", "b": "ev:U-SecondaryEventsKim14", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-CM577", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-CM577", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:gastric", "b": "ev:U-DANTE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CD274", "b": "ev:U-DANTE", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-DANTE", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-MSI", "b": "ev:U-DANTE", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-PETRARCA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-PETRARCA", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-PETRARCA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-COMPASSION15", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-COMPASSION15", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-COMPASSION15", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-KN756", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-KN756", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-KN756", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CM7FL", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-CM7FL", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-CM7FL", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-PDL1-B", "b": "ev:U-CM7FL", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-KRISTINE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-KRISTINE", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-KRISTINE", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-MONARCH2", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-MONARCH2", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-MONARCH2", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-ML7", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-ML7", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-ML7", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-PATINA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-PATINA", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "tgt:ERBB2", "b": "ev:U-PATINA", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-PATINA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-HR", "b": "ev:U-PATINA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-ctDNAEGCpCR24", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-ctDNAGC25", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-ctDNAGarcia19", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-ctDNAISPY23", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HR", "b": "ev:U-ctDNAISPY23", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-ctDNALate22", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HR", "b": "ev:U-ctDNALate22", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-ctDNALongit25", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-ZETA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-EXAM", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-ARROW", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-LaroThyroid22", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-PTMCObserveAge14", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-PTCSurveillanceUS17", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-IM050", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-IM050", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "tgt:CD274", "b": "ev:U-IM050", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-IM050", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CDK46TTE26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-CDK46TTE26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-CDK46TTE26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-RSNodes26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HR", "b": "ev:U-RSNodes26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-GCMMA26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-BMPP826", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-GCGULP126", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-GCGULP126", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "tgt:CD274", "b": "ev:U-GCGULP126", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-FANCMAdapt26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-GDSCOxali26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-TDM1Liver26", "rel": "evidence belongs to 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"ev:U-SUV39H2Splice26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:colorectal", "b": "ev:U-CodeBreaK300", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-KRYSTAL1CRC", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-FRESCO2", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:KDR", "b": "ev:U-FRESCO2", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:colorectal", "b": "ev:U-RECOURSE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-PARADIGM", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-BREAKWATER", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-ATOMIC", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CD274", "b": "ev:U-ATOMIC", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-MSI-C", "b": "ev:U-ATOMIC", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:colorectal", "b": "ev:U-IDEA18", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-GEMSTONE303", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CD274", "b": "ev:U-GEMSTONE303", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-PDL1-CPS", "b": "ev:U-GEMSTONE303", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-ESOPEC", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-NeoAEGIS", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-EXPEL", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-ML3", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-ML3", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-ML3", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-PALOMA2", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-PALOMA2", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-PALOMA2", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-NALA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-NALA", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-NALA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-HER2CLIMB02", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2CLIMB02", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-HER2CLIMB02", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-PHILA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-PHILA", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-PHILA", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:thyroid", "b": "ev:U-T-ESTIMABL2", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-IoN", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-HiLo", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-ESTIMABL1", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-ASTRA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-PTMCSurveillanceKR18", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-PMCObserveJP10", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-INFLUENCEBE26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-HER2Lactylation26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2Lactylation26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-G", "b": "ev:U-HER2Lactylation26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CDK1Dynamics26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-CDK1Dynamics26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HR", "b": "ev:U-CDK1Dynamics26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-CLASP26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-MetastaticLatency26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-Ganetespib26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-HR", "b": "ev:U-Ganetespib26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-ESR1VariantTOT26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ESR1", "b": "ev:U-ESR1VariantTOT26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-ESR1", "b": "ev:U-ESR1VariantTOT26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:colorectal", "b": "ev:U-CRLMMultistate26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-S100RAGETDXd26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-S100RAGETDXd26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-S100RAGETDXd26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:colorectal", "b": "ev:U-AkkMSSCRC26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-AkkMSSCRC26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-MechanisticRelapse26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-PaxalisibBrain26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-PaxalisibBrain26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-PaxalisibBrain26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-HypoMastIMNI26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:gastric", "b": "ev:U-nacGSOXLong26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-ALASCCA", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-CHALLENGE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-LEAP017", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-DCRC02", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-DCRC02", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:colorectal", "b": "ev:U-AtezoTRIBE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CD274", "b": "ev:U-AtezoTRIBE", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:thyroid", "b": "ev:U-T-LENVA211", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-Donafenib23", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-ALTER01031", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "an:A8", "b": "ev:U-A8", "rel": "analysis is recorded as this unit", "src": "derived" }, { "a": "prog:colorectal", "b": "ev:U-A8", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "bm:BM-MSI-C", "b": "ev:U-A8", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-TDXdILA26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-TDXdILA26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-EosinophilHR26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:CDK4/6", "b": "ev:U-EosinophilHR26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-ACTOrganoid26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-QBS72S26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "an:A9", "b": "ev:U-A9", "rel": "analysis is recorded as this unit", "src": "derived" }, { "a": "prog:thyroid", "b": "ev:U-A9", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-PD1MaintenanceCRC26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-PD1MaintenanceCRC26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-MSI-C", "b": "ev:U-PD1MaintenanceCRC26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:gastric", "b": "ev:U-FABP4Peritoneal26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-HER2ResidualDiscord26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2ResidualDiscord26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-HER2ResidualDiscord26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "bm:BM-HER2LOW-B", "b": "ev:U-HER2ResidualDiscord26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:breast", "b": "ev:U-INTEGRAL26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-INTEGRAL26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:colorectal", "b": "ev:U-FIRE3", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-CALGB80405", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-TRIPLETE", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-JCOG0603", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:thyroid", "b": "ev:U-T-DABTHY", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-NabDDHR26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:colorectal", "b": "ev:U-CRPMctDNA26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "prog:breast", "b": "ev:U-HER2CR26", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-HER2CR26", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-HER2CR26", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "prog:colorectal", "b": "ev:U-CA2098M4", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:PDCD1", "b": "ev:U-CA2098M4", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "prog:breast", "b": "ev:U-UCI1467", "rel": "evidence belongs to this programme", "src": "curated: unit.program" }, { "a": "tgt:ERBB2", "b": "ev:U-UCI1467", "rel": "unit is tagged with this target; no readiness claim", "src": "curated: unit.targets" }, { "a": "bm:BM-HER2-B", "b": "ev:U-UCI1467", "rel": "unit records this biomarker", "src": "curated: unit.biomarkers" }, { "a": "qp:QP-01", "b": "ev:U-HER2Fab", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-HER2Pert", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-ToGA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-DG04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-GATSBY", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-JACOB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-LOGiC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-TyTAN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-Hofmann08", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-GEAHER2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "ev:U-A1", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-01", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-01", "b": "bm:BM-HER2-G", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-01", "b": "bm:BM-HER2-B", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-02", "b": "ev:U-SOLAR1", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-02", "b": "ev:U-INAVO120", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-02", "b": "ev:U-ERago", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-02", "b": "ev:U-EMERALD", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-02", "b": "ev:U-AF3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-02", "b": "tgt:PIK3CA", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-02", "b": "tgt:ESR1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-03", "b": "ev:U-SPOTLIGHT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-CT041", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-KN859", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-KN061", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-DG01", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-DG04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-IMP130", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-IMP131", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-DB03", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "ev:U-DG04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-03", "b": "bm:BM-CLDN18", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-03", "b": "bm:BM-PDL1-CPS", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-03", "b": "bm:BM-PDL1-TAP", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-04", "b": "ev:U-PALLAS", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-PENELOPEB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-monarchE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-NATALEE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-GATSBY", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-JACOB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-LOGiC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-RAINFALL", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "ev:U-RINDBeRG", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-04", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-04", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-05", "b": "ev:U-A1", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-05", "b": "ev:U-A3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-05", "b": "ev:U-A1", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-05", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-05", "b": "ev:U-A5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "ev:U-GASTHER3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "ev:U-HER2loss16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "ev:U-GASTHER3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "ev:U-DG02", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "ev:U-DG04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-06", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-06", "b": "bm:BM-HER2-G", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-06", "b": "bm:BM-HER2HET", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-06", "b": "bm:BM-pERBB2", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-07", "b": "ev:U-SPOTLIGHT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-07", "b": "ev:U-CT041", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-07", "b": "tgt:CLDN18.2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-07", "b": "bm:BM-CLDN18", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-08", "b": "ev:U-PADA1", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "ev:U-SERENA6", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "ev:U-SERENA6", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "ev:U-A5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-08", "b": "tgt:ESR1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-08", "b": "bm:BM-ESR1", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-09", "b": "ev:U-CM649", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-09", "b": "ev:U-RAT305", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-09", "b": "ev:U-KN859", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-09", "b": "ev:U-IMP130", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-09", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-09", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-09", "b": "bm:BM-PDL1-CPS", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-09", "b": "bm:BM-PDL1-TAP", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-10", "b": "ev:U-DB04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-10", "b": "ev:U-DB06", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-10", "b": "ev:U-ASCOCAP23", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-10", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-10", "b": "bm:BM-HER2LOW-B", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-10", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-11", "b": "ev:U-DB04", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-11", "b": "ev:U-TROPiCS02", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-11", "b": "ev:U-TROPIONB01", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-11", "b": "ev:U-ADCLow", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-11", "b": "ev:U-ADCSequence84", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-11", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-11", "b": "tgt:TACSTD2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-12", "b": "ev:U-AFServer", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-12", "b": "ev:U-AF3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-12", "b": "ev:U-AFDB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-13", "b": "ev:U-A3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-13", "b": "ev:U-AFDB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-13", "b": "tgt:CLDN18.2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-13", "b": "bm:BM-CLDN18", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-14", "b": "ev:U-CT041", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-monarchE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-OlympiA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-SOFT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-ASTRRA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-ATLAS", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-NSABPB42", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-Razavi18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-SALSA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-NATALEE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-14", "b": "ev:U-OlympiA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-15", "b": "ev:U-DS8201pre16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-15", "b": "ev:U-SGpre15", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-15", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-15", "b": "tgt:TACSTD2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-16", "b": "ev:U-ZOLpre24", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-16", "b": "ev:U-ZOLpre24", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-16", "b": "ev:U-A3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-16", "b": "tgt:CLDN18.2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-17", "b": "ev:U-AZD5363pre12", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-17", "b": "ev:U-PD0332991pre09", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-17", "b": "tgt:AKT", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-17", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-18", "b": "ev:U-PD1Rupp22", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-18", "b": "ev:U-PDL1Glyco16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-18", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-18", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-19", "b": "ev:U-FGFR2Xie13", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-19", "b": "ev:U-VEGFR2Mashima21", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-19", "b": "tgt:FGFR2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-19", "b": "tgt:KDR", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-20", "b": "ev:U-FLOT4", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-ACTSGC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-JACCROGC07", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-ARTIST2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-PRODIGY", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-TOPGEAR", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-ARTIST", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-KATHERINE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-IMP030", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-CREATEX", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "ev:U-EA1131", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-20", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-20", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-21", "b": "ev:U-ctDNAYang20", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-21", "b": "ev:U-ctDNAYuan23", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-21", "b": "ev:U-ctDNAYang20", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-21", "b": "ev:U-ctDNAYuan23", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-22", "b": "ev:U-cTRAKTN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-22", "b": "ev:U-cTRAKTN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-22", "b": "ev:U-cTRAKTN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-22", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-23", "b": "ev:U-NICHE2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-23", "b": "ev:U-DOSTrectal", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-23", "b": "ev:U-KN177", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-23", "b": "ev:U-CM8HW", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-23", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-23", "b": "bm:BM-MSI-C", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-24", "b": "ev:U-DYNAMIC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-24", "b": "ev:U-DYNAMIC3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-24", "b": "ev:U-GALAXY", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-24", "b": "ev:U-ctDNAYang20", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-24", "b": "ev:U-ctDNAYuan23", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-24", "b": "ev:U-cTRAKTN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-25", "b": "ev:U-KoreaThyScreen16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-25", "b": "ev:U-KoreaThyScreen16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-26", "b": "ev:U-HashimotoPTC17", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-26", "b": "ev:U-HashimotoPTC17", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-SELECT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-DECISION", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-COSMIC311", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-LIBRETTO001", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-LIBRETTO531", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-27", "b": "ev:U-T-ROAR", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-28", "b": "ev:U-HER2Residual26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-28", "b": "ev:U-HER2Residual26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-28", "b": "ev:U-KATHERINE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-28", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-28", "b": "bm:BM-HER2-B", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-29", "b": "ev:U-TROPIONB01", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "ev:U-EGF100151", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "ev:U-JAVG100", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "ev:U-EMBRACA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "ev:U-AVAGAST", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "ev:U-ATTR4", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-29", "b": "tgt:TACSTD2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-29", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-29", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-29", "b": "tgt:PARP1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-29", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-29", "b": "bm:BM-gBRCA", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-30", "b": "ev:U-KN522", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-30", "b": "ev:U-monarchE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-30", "b": "ev:U-CLASSIC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-30", "b": "ev:U-KN585", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-30", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-30", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-31", "b": "ev:U-MATTERHORN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-31", "b": "ev:U-KN522", "rel": "cited as 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pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-CCNE1TDXd24", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-CCNE1Rustgi24", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-CCNE1Lee15", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-HER2GCKwon23", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-CyclinEScaltriti11", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-CyclinELuhtala16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-Janjigian18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-AMNESIA18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "ev:U-JACOB", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-62", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-62", "b": "bm:BM-COAMP", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-63", "b": "ev:U-FOxTROT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-63", "b": "ev:U-NICHE2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-63", "b": "ev:U-FOxTROT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-63", "b": "ev:U-NICHE2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-63", "b": "bm:BM-MSI-C", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-64", "b": "ev:U-KN756", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-64", "b": "ev:U-CM7FL", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-64", "b": "ev:U-CM7FL", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-64", "b": "ev:U-KN522", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-64", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-64", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-65", "b": "ev:U-KRISTINE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-65", "b": "ev:U-PHERGain", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-65", "b": "ev:U-KRISTINE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-65", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" 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"curated: pair.biomarkers" }, { "a": "qp:QP-67", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-67", "b": "ev:U-A5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-67", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-67", "b": "ev:U-A2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-67", "b": "ev:U-A5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-67", "b": "tgt:ESR1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-67", "b": "bm:BM-ESR1", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-68", "b": "ev:U-CM577", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-68", "b": "ev:U-ATT5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-68", "b": "ev:U-VESTIGE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-68", "b": "ev:U-CM577", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-68", "b": "ev:U-ATT5", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-68", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-69", "b": "ev:U-ctDNAGarcia19", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-ctDNALate22", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-ctDNAGC25", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-ctDNAEGCpCR24", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-ctDNAGarcia19", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-ctDNALate22", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-69", "b": "ev:U-cTRAKTN", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-70", "b": "ev:U-IM050", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-70", "b": "ev:U-IM050", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-70", "b": "ev:U-IM050", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-70", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-70", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-70", "b": "bm:BM-HER2-B", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-71", "b": "ev:U-CDK46TTE26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-71", "b": "ev:U-CDK46TTE26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-71", "b": "ev:U-CDK46TTE26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-71", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-71", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-72", "b": "ev:U-RSNodes26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-72", "b": "ev:U-RSNodes26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-72", "b": "ev:U-RxPONDER", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-72", "b": "ev:U-RSNodes26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-72", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-73", "b": "ev:U-GCMMA26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-73", "b": "ev:U-BMPP826", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-74", "b": "ev:U-FANCMAdapt26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-74", "b": "ev:U-FANCMAdapt26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-75", "b": "ev:U-GDSCOxali26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-75", "b": "ev:U-GDSCOxali26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-75", "b": "ev:U-GDSCOxali26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-75", "b": "ev:U-GDSCOxali26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-76", "b": "ev:U-TDM1Liver26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-76", "b": "ev:U-TDM1Liver26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-76", "b": "tgt:ERBB2", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-76", "b": "bm:BM-HER2-B", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-77", "b": "ev:U-MLH1Punctate26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-77", "b": "ev:U-MLH1Punctate26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-77", "b": "bm:BM-MSI-C", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-78", "b": "ev:U-ERLowOmission26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-78", "b": "ev:U-ERLowOmission26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-78", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-79", "b": "ev:U-SUV39H2Splice26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-79", "b": "ev:U-SUV39H2Splice26", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-79", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-80", "b": "ev:U-T-ZETA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-80", "b": "ev:U-T-EXAM", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-80", "b": "ev:U-T-LIBRETTO531", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-81", "b": "ev:U-PTMCObserveAge14", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-81", "b": "ev:U-PTCSurveillanceUS17", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-81", "b": "ev:U-PTMCObserveAge14", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-81", "b": "ev:U-PTCSurveillanceUS17", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-81", "b": "ev:U-KoreaThyScreen16", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-82", "b": "ev:U-T-ARROW", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-82", "b": "ev:U-T-LIBRETTO001", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-82", "b": "ev:U-T-LIBRETTO531", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-83", "b": "ev:U-CodeBreaK300", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-83", "b": "ev:U-CodeBreaK300", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-83", "b": "ev:U-KRYSTAL1CRC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-84", "b": "ev:U-RECOURSE", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-84", "b": "ev:U-FRESCO2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-84", "b": "ev:U-SUNLIGHT", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-85", "b": "ev:U-IDEA18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-85", "b": "ev:U-IDEA18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-85", "b": "ev:U-MOSAIC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-85", "b": "ev:U-IDEA18", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-86", "b": "ev:U-BREAKWATER", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-86", "b": "ev:U-BREAKWATER", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-86", "b": "ev:U-BEACON", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-87", "b": "ev:U-ATOMIC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-87", "b": "ev:U-ATOMIC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-87", "b": "ev:U-NICHE2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-87", "b": "tgt:CD274", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-87", "b": "bm:BM-MSI-C", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-88", "b": "ev:U-PALOMA2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-PALOMA3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-ML2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-ML3", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-ML7", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-MONARCH2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-PALOMA2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-ML7", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "ev:U-MONARCH2", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-88", "b": "tgt:CDK4/6", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-88", "b": "bm:BM-HR", "rel": "question about this biomarker", "src": "curated: pair.biomarkers" }, { "a": "qp:QP-89", "b": "ev:U-ESOPEC", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-89", "b": "ev:U-NeoAEGIS", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-89", "b": "ev:U-CM577", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-89", "b": "tgt:PDCD1", "rel": "question about this target", "src": "curated: pair.targets" }, { "a": "qp:QP-90", "b": "ev:U-NALA", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-90", "b": "ev:U-HER2CLIMB02", "rel": "cited as basis for the judgment", "src": "curated: pair.basis" }, { "a": "qp:QP-90", "b": "ev:U-HER2CLIMB", "rel": "cited as basis for the judgment", 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perioperative pathologic response", "count": 580 }, { "id": "ev:U-NEONIPIGA", "label": "NEONIPIGA · single-arm perioperative immunotherapy", "count": 32 }, { "id": "ev:U-DB11", "label": "DESTINY-Breast11 · neoadjuvant HER2 regimen comparison", "count": 927 }, { "id": "ev:U-NeoPACT", "label": "NeoPACT · single-arm anthracycline-free chemoimmunotherapy", "count": 120 }, { "id": "ev:U-evERA", "label": "evERA Breast Cancer", "count": 373 }, { "id": "ev:U-NEO", "label": "NEO / CO.28 — organ preservation and ctDNA", "count": 58 }, { "id": "ev:U-MOUNTAINEER", "label": "MOUNTAINEER · tucatinib plus trastuzumab in HER2-positive colorectal cancer", "count": 117 }, { "id": "ev:U-DCRC01", "label": "DESTINY-CRC01 · trastuzumab deruxtecan by HER2 expression level in colorectal cancer", "count": 86 }, { "id": "ev:U-BEACON", "label": "BEACON CRC · encorafenib plus cetuximab in BRAF V600E colorectal cancer", "count": 702 }, { "id": "ev:U-KN355", "label": "KEYNOTE-355 · pembrolizumab plus chemotherapy by PD-L1 score", "count": 882 }, { "id": "ev:U-ML2", "label": "MONALEESA-2 · first-line ribociclib plus letrozole", "count": 668 }, { "id": "ev:U-DB02", "label": "DESTINY-Breast02", "count": 608 }, { "id": "ev:U-OPRA", "label": "OPRA · watch-and-wait after total neoadjuvant therapy", "count": 358 }, { "id": "ev:U-FOxTROT", "label": "FOxTROT · preoperative chemotherapy for operable colon cancer", "count": 1053 }, { "id": "ev:U-CM142", "label": "CheckMate 142 · nivolumab with or without ipilimumab", "count": 385 }, { "id": "ev:U-PHERGain", "label": "PHERGain · PET- and response-adapted chemotherapy de-escalation", "count": 377 }, { "id": "ev:U-APHINITY", "label": "APHINITY · adjuvant pertuzumab added to trastuzumab and chemotherapy", "count": 4804 }, { "id": "ev:U-PALOMA3", "label": "PALOMA-3 · palbociclib plus fulvestrant after endocrine therapy", "count": 521 }, { "id": "ev:U-ORIENT16", "label": "ORIENT-16 · first-line sintilimab plus chemotherapy", "count": 650 }, { "id": "ev:U-ARMANI", "label": "ARMANI · switch maintenance with ramucirumab plus paclitaxel", "count": 280 }, { "id": "ev:U-CM577", "label": "CheckMate 577 · adjuvant nivolumab after chemoradiotherapy and surgery", "count": 794 }, { "id": "ev:U-DANTE", "label": "DANTE · perioperative atezolizumab plus FLOT, interim", "count": 677 }, { "id": "ev:U-PETRARCA", "label": "PETRARCA · perioperative trastuzumab and pertuzumab with FLOT", "count": 81 }, { "id": "ev:U-COMPASSION15", "label": "COMPASSION-15 · first-line cadonilimab plus chemotherapy", "count": 610 }, { "id": "ev:U-KN756", "label": "KEYNOTE-756 · neoadjuvant pembrolizumab in ER-positive early breast cancer", "count": 1240 }, { "id": "ev:U-CM7FL", "label": "CheckMate 7FL · neoadjuvant nivolumab in ER-positive early breast cancer", "count": 521 }, { "id": "ev:U-KRISTINE", "label": "KRISTINE · neoadjuvant T-DM1 plus pertuzumab without conventional chemotherapy", "count": 444 }, { "id": "ev:U-MONARCH2", "label": "MONARCH 2 · abemaciclib plus fulvestrant after endocrine therapy", "count": 669 }, { "id": "ev:U-ML7", "label": "MONALEESA-7 · ribociclib plus endocrine therapy before menopause", "count": 672 }, { "id": "ev:U-PATINA", "label": "PATINA · palbociclib added to maintenance HER2 and endocrine therapy", "count": 518 }, { "id": "ev:U-T-ZETA", "label": "ZETA (vandetanib, medullary thyroid cancer)", "count": 331 }, { "id": "ev:U-T-EXAM", "label": "EXAM (cabozantinib, medullary thyroid cancer)", "count": 330 }, { "id": "ev:U-T-ARROW", "label": "ARROW (pralsetinib, RET-altered thyroid cohorts)", "count": 590 }, { "id": "ev:U-T-LaroThyroid22", "label": "Larotrectinib in TRK fusion-positive thyroid carcinoma · pooled analysis of three trials", "count": 215 }, { "id": "ev:U-IM050", "label": "IMpassion050: primary response and final follow-up", "count": 454 }, { "id": "ev:U-CodeBreaK300", "label": "CodeBreaK 300 · sotorasib plus panitumumab in KRAS G12C colorectal cancer", "count": 160 }, { "id": "ev:U-KRYSTAL1CRC", "label": "KRYSTAL-1 · adagrasib with or without cetuximab in KRAS G12C colorectal cancer", "count": 731 }, { "id": "ev:U-FRESCO2", "label": "FRESCO-2 · fruquintinib versus placebo in refractory colorectal cancer", "count": 691 }, { "id": "ev:U-RECOURSE", "label": "RECOURSE · TAS-102 versus placebo in refractory colorectal cancer", "count": 800 }, { "id": "ev:U-PARADIGM", "label": "PARADIGM · panitumumab versus bevacizumab with first-line chemotherapy by tumour side", "count": 823 }, { "id": "ev:U-BREAKWATER", "label": "BREAKWATER · first-line encorafenib, cetuximab and mFOLFOX6 in BRAF V600E colorectal cancer", "count": 841 }, { "id": "ev:U-ATOMIC", "label": "ATOMIC · adjuvant atezolizumab with FOLFOX in stage III dMMR colon cancer", "count": 712 }, { "id": "ev:U-GEMSTONE303", "label": "GEMSTONE-303 · first-line sugemalimab in PD-L1 CPS ≥5 disease", "count": 479 }, { "id": "ev:U-ESOPEC", "label": "ESOPEC · perioperative FLOT versus preoperative chemoradiotherapy", "count": 438 }, { "id": "ev:U-NeoAEGIS", "label": "Neo-AEGIS · chemoradiotherapy versus perioperative chemotherapy", "count": 377 }, { "id": "ev:U-EXPEL", "label": "EXPEL · extensive peritoneal lavage after gastrectomy", "count": 600 }, { "id": "ev:U-ML3", "label": "MONALEESA-3 · ribociclib plus fulvestrant", "count": 726 }, { "id": "ev:U-PALOMA2", "label": "PALOMA-2 · first-line palbociclib plus letrozole", "count": 666 }, { "id": "ev:U-NALA", "label": "NALA · neratinib versus lapatinib, each with capecitabine", "count": 621 }, { "id": "ev:U-HER2CLIMB02", "label": "HER2CLIMB-02 · tucatinib added to T-DM1", "count": 466 }, { "id": "ev:U-PHILA", "label": "PHILA · first-line pyrotinib with trastuzumab and docetaxel", "count": 590 }, { "id": "ev:U-T-ESTIMABL2", "label": "ESTIMABL2 · thyroidectomy with or without radioiodine in low-risk thyroid cancer", "count": 776 }, { "id": "ev:U-T-IoN", "label": "IoN · thyroidectomy with or without radioiodine ablation in the United Kingdom", "count": 504 }, { "id": "ev:U-T-HiLo", "label": "HiLo · low-dose versus high-dose radioiodine ablation", "count": 438 }, { "id": "ev:U-T-ESTIMABL1", "label": "ESTIMABL1 · radioiodine dose and stimulation method in low-risk thyroid cancer", "count": 950 }, { "id": "ev:U-T-ASTRA", "label": "ASTRA · selumetinib added to adjuvant radioactive iodine in high-risk differentiated thyroid cancer", "count": 233 }, { "id": "ev:U-Ganetespib26", "label": "Fulvestrant with ganetespib in endocrine resistance: negative randomized phase II result", "count": 50 }, { "id": "ev:U-AkkMSSCRC26", "label": "Akkermansia and PD-1 blockade in MSS colorectal cancer: early combination signal", "count": 22 }, { "id": "ev:U-PaxalisibBrain26", "label": "Paxalisib plus trastuzumab: no confirmed CNS responses at the recommended dose", "count": 17 }, { "id": "ev:U-HypoMastIMNI26", "label": "HypoMast-IMNI: locoregional noninferiority and reduced acute skin toxicity", "count": 1494 }, { "id": "ev:U-ALASCCA", "label": "ALASCCA · low-dose aspirin after surgery for PI3K-altered colorectal cancer", "count": 626 }, { "id": "ev:U-CHALLENGE", "label": "CHALLENGE · structured exercise programme after adjuvant chemotherapy for colon cancer", "count": 889 }, { "id": "ev:U-LEAP017", "label": "LEAP-017 · lenvatinib plus pembrolizumab in previously treated pMMR colorectal cancer", "count": 563 }, { "id": "ev:U-DCRC02", "label": "DESTINY-CRC02 · two doses of trastuzumab deruxtecan in HER2-positive colorectal cancer", "count": 122 }, { "id": "ev:U-AtezoTRIBE", "label": "AtezoTRIBE · atezolizumab added to first-line FOLFOXIRI and bevacizumab", "count": 218 }, { "id": "ev:U-T-LENVA211", "label": "Study 211 · lenvatinib starting dose 18 mg versus 24 mg in radioiodine-refractory thyroid cancer", "count": 241 }, { "id": "ev:U-T-ALTER01031", "label": "ALTER 01031 · anlotinib in advanced medullary thyroid carcinoma", "count": 91 }, { "id": "ev:U-QBS72S26", "label": "QBS72S: separate leptomeningeal observations and parenchymal response cohort", "count": 21 }, { "id": "ev:U-INTEGRAL26", "label": "INTEGRAL: early termination of intratumoral IL-12 combination in anthracycline-refractory TNBC", "count": 8 }, { "id": "ev:U-FIRE3", "label": "FIRE-3 · FOLFIRI with cetuximab or bevacizumab as first-line treatment", "count": 568 }, { "id": "ev:U-CALGB80405", "label": "CALGB/SWOG 80405 · cetuximab or bevacizumab with first-line chemotherapy", "count": 2334 }, { "id": "ev:U-TRIPLETE", "label": "TRIPLETE · mFOLFOXIRI versus modified FOLFOX with panitumumab", "count": 435 }, { "id": "ev:U-T-DABTHY", "label": "Dabrafenib versus dabrafenib plus trametinib in BRAF-mutated radioiodine-refractory thyroid cancer", "count": 53 }, { "id": "ev:U-NabDDHR26", "label": "Dose-dense nab-paclitaxel versus docetaxel in HR-positive early breast cancer", "count": 100 }, { "id": "ev:U-HER2CR26", "label": "HER2-CR: residual ctDNA in durable responders with metastatic breast cancer", "count": 50 }, { "id": "ev:U-CA2098M4", "label": "CA209-8M4: nivolumab plus total neoadjuvant therapy for rectal cancer", "count": 29 }, { "id": "ev:U-UCI1467", "label": "UCI 14-67: first posted neoadjuvant results by HER2 status", "count": 120 }, { "id": "ds:D-STAD", "label": "TCGA Stomach Adenocarcinoma (PanCancer Atlas)", "count": 440438 }, { "id": "ds:D-BRCA", "label": "TCGA Breast Invasive Carcinoma (PanCancer Atlas)", "count": 108410701066 }, { "id": "ds:D-MSK18", "label": "Breast Cancer (MSK, Cancer Cell 2018)", "count": 19189181000 }, { "id": "ds:D-METABRIC", "label": "METABRIC", "count": 1980 }, { "id": "ds:D-THCA", "label": "TCGA Thyroid Carcinoma (PanCancer Atlas) with GDC clinical table", "count": 507490 }, { "id": "ds:D-CRCMSK", "label": "Metastatic Colorectal Cancer (MSK, Cancer Cell 2018)", "count": 11341099601533 }, { "id": "ds:D-CRCMSK26", "label": "Colorectal Adenocarcinoma (MSK, 2026)", "count": 723767896513 }, { "id": "ds:D-MSK50K", "label": "MSK-IMPACT 50K Clinical Sequencing Cohort (MSK, Cancer Cell 2026)", "count": 543318677229 } ] }, { "id": "program", "label": "Research Program", "of": "Core programmes and authorised extensions", "nodes": [ { "id": "prog:gastric", "label": "Gastric Cancer", "count": 89 }, { "id": "prog:breast", "label": "Breast Cancer", "count": 144 }, { "id": "prog:colorectal", "label": "Colorectal Cancer", "count": 49 }, { "id": "prog:thyroid", "label": "Thyroid Cancer", "count": 48 }, { "id": "prog:gxb", "label": "Gastric × Breast", "count": 2 }, { "id": "prog:expansion", "label": "Expansion Programs", "count": 1 } ] } ], "work": { "gaps": [ { "id": "QP-07", "kind": "Claim with no source in the library", "text": "두 기준의 일치율을 직접 평가한 자료는 이 판단의 근거로 아직 연결하지 않았다.", "need": "판정 기준을 Biomarker Atlas 의 CLDN18.2 항목에 두 줄로 적는다" }, { "id": "QP-04", "kind": "Judgment held pending evidence", "text": "상충 결과가 나왔을 때 가설을 보류함", "need": "보류한 가설이 설계를 고친 연구에서 재현되면 되살린다. 유예 사유는 연구 시작 전에 적어 둔 것만 인정한다." }, { "id": "QP-08", "kind": "Judgment held pending evidence", "text": "진행 전 교체의 이득을 무엇으로 셀 것인가", "need": "같은 시험의 성숙한 전체 생존, 후속 치료 이후 결과, 삶의 질과 위해가 공개되면 각 평가변수의 판단을 갱신한다. 관찰 분석의 방향만으로 임상 결론을 대신하지 않는다." }, { "id": "QP-11", "kind": "Judgment held pending evidence", "text": "ADC를 이어 쓴 결과를 무엇으로 추정하는가", "need": "순서를 직접 비교한 무작위 연구나 대상군·치료 차수·평가 시작 시점·교란 보정이 명확한 비교 관찰 연구가 들어오면 해당 범위의 판단을 갱신한다. 방법 절에서 확인한 평가변수 차이를 유지하고, 아직 검토하지 않은 정량적 안전성과 보충자료를 따로 확인한다." }, { "id": "QP-12", "kind": "Judgment held pending evidence", "text": "예측 서버 출력을 자동 검색에 연결함", "need": "RISCON Labs 의 법적 지위와 이용 목적이 약관상 비상업으로 확인되면 개별 예측 작업만 연다. 스크리닝 연결은 그와 무관하게 열지 않는다." }, { "id": "QP-15", "kind": "Judgment held pending evidence", "text": "접합체의 작용과 표적 의존성을 구별함", "need": "약물 전달 효과를 구분한 비교 자료에 더해 표적의 유전적 변화가 종양 생존을 좌우한다는 독립된 근거가 연결되면, 해당 모델에 한해 신호 의존성도 별도로 기록한다. 순서 판단은 순서를 직접 비교한 자료가 들어올 때 다시 검토한다." }, { "id": "QP-17", "kind": "Judgment held pending evidence", "text": "억제제 감수성은 분자 맥락을 붙여 읽는다", "need": "후보 특징을 미리 정한 독립 모델에서 민감군과 저항군의 구분이 재현되면 선별 가설의 근거를 보강한다. 환자 적용 판단은 검사 기준과 치료 결과를 함께 검증한 별도의 임상 자료가 들어오면 갱신한다." }, { "id": "QP-20", "kind": "Judgment held pending evidence", "text": "수술 전후의 성적은 맥락을 맞춰 읽음", "need": "같은 대상군과 평가변수로 치료 전략을 직접 비교한 결과가 공개되면 해당 맥락에서 상대 효과를 판단한다. 간접 비교는 대상군과 대조군의 연결 가능성을 검토한 자료가 있을 때 범위를 정해 다시 살핀다." }, { "id": "QP-21", "kind": "Judgment held pending evidence", "text": "재발 예측과 치료 이득을 따로 판정한다", "need": "검사에 따른 개입 전략을 사전에 정하고 적절한 대조군과 비교해 재발·생존 및 위해를 평가한 결과가 확보되면 임상적 유용성을 별도로 판단한다. 검출률이나 위험 예측 성능의 개선만으로 이 판단을 바꾸지는 않는다." }, { "id": "QP-22", "kind": "Judgment held pending evidence", "text": "혈액 신호가 개입의 기회를 보장하는가", "need": "더 이른 검출이 영상상 재발 전 개입에 실제로 연결되는지 확인하고, 충분한 규모의 비교 연구가 재발·생존과 위해를 평가하면 검사 기반 전략을 다시 판단한다. 신호 소실이 좋아져도 환자 결과의 개선은 별도로 확인한다." }, { "id": "QP-23", "kind": "Judgment held pending evidence", "text": "완전반응 뒤에도 완치는 따로 확인함", "need": "같은 대상군과 평가 기준에서 충분히 성숙한 재발·전체 생존 및 구제치료 자료가 축적되고 독립된 연구에서도 지속성이 확인되면 완치와 관련한 판단을 다시 평가한다. 반응률 상승이나 영상상 소실만으로는 이 판단을 바꾸지 않는다." }, { "id": "QP-24", "kind": "Judgment held pending evidence", "text": "암종을 옮긴 잔존 신호의 유용성은 보류", "need": "대상 암종과 병기에서 검사 시점과 개입 규칙을 사전에 정한 비교 연구가 재발·생존과 위해를 평가하면 판단을 바꿀 수 있다. 검출률이나 위험 예측 성능만 좋아진 경우에는 환자 결과에 대한 판단을 유지한다." }, { "id": "QP-25", "kind": "Judgment held pending evidence", "text": "늘어난 진단과 검진의 이득은 별개", "need": "대상군과 관찰기간을 맞춘 비교 자료가 검진 노출, 갑상선암 사망과 진단·치료의 위해를 함께 평가하고 지역 차이를 넘어 같은 방향을 보이면 이득과 위해에 대한 판단을 갱신한다. 발견 건수의 증가만으로는 판단을 바꾸지 않는다." }, { "id": "QP-26", "kind": "Judgment held pending evidence", "text": "갑상선염과 암의 동반에서 인과를 보류", "need": "일반 인구에서 출발한 전향적 자료가 갑상선염의 선행 여부를 확인하고 검사 빈도와 관련 요인을 고려한 뒤에도 새 유두암 발생의 차이를 일관되게 보이면 인과 가설의 근거를 강화한다. 그래도 관찰 연관성만으로 확정된 원인이라고 기록하지 않는다." }, { "id": "QP-27", "kind": "Judgment held pending evidence", "text": "반응률은 비교 시험의 결론을 대신 못함", "need": "같은 조직형, 분자 선별 기준과 치료 이력에서 적절한 비교 연구가 사전에 정한 평가변수와 위해를 함께 검증하면 상대 효과 판단을 갱신한다. 새 단일군 보고가 추가된 경우에는 활성의 재현성을 보강하되 비교 효과의 근거 등급을 자동으로 올리지 않는다." }, { "id": "QP-28", "kind": "Judgment held pending evidence", "text": "잔존암의 표적 변화는 약효 증거와 별개", "need": "더 큰 별도 환자군에서 같은 판정 기준으로 얻은 비교 결과와 불확실성, 또는 재검사 기반 선택 전략의 임상 결과가 확보되면 판단을 갱신한다. 다른 접합체의 전체 시험 결과만으로 이 하위군의 이득을 대신하지 않는다." }, { "id": "QP-29", "kind": "Judgment held pending evidence", "text": "진행 억제와 생존 개선을 따로 판정", "need": "사전에 정한 전체 생존 기준을 충족하는 후속 결과나 정정이 공개되면 갱신한다. 보정 분석은 보조 근거로만 다루고 탐색적 하위군이나 생존자 조건부 관찰만으로 일차 판정을 뒤집지 않는다." }, { "id": "QP-30", "kind": "Judgment held pending evidence", "text": "장기 추적에 맞춰 생존 판단을 고침", "need": "사전 분석계획과 맞는 추가 추적이나 정정이 효과의 방향·크기·불확실성을 바꾸면 해당 시험의 판단을 갱신한다. 초기 반응을 다른 연구의 장기 생존 대신 쓰려면 그 대리 관계를 별도로 검증한 근거가 필요하다." }, { "id": "QP-31", "kind": "Judgment held pending evidence", "text": "수술 전후 병용의 기여는 분리 못함", "need": "수술 전 치료가 같은 환자들을 수술 후 치료 유무로 무작위 비교하거나, 각 단계의 기여를 구분하도록 미리 설계한 비교 근거가 확보되면 단계별 판단을 갱신한다. 투여를 마친 환자의 결과가 좋다는 관찰만으로 특정 단계를 생략할 수 있다고 결론 내리지 않는다." }, { "id": "QP-32", "kind": "Judgment held pending evidence", "text": "잔존암 약효와 폐 위해를 함께 읽음", "need": "같은 시험의 성숙한 전체 생존과 장기 안전성 결과가 공개되면 이득과 위해의 판단을 함께 갱신한다. 등록 조건 밖의 잔존암으로 범위를 넓히려면 그 집단을 포함한 비교 근거가 필요하며, 두 시험의 수치를 단순 비교한 결과만으로 확대하지 않는다." }, { "id": "QP-33", "kind": "Judgment held pending evidence", "text": "선별된 진행성 병용 결과의 적용 범위", "need": "사전 계획에 따른 성숙한 전체 생존 결과가 나오면 해당 선별 집단의 판단을 갱신한다. 다른 피디엘원 상태나 초기암에 대한 비교 자료, 각 약제의 추가 기여를 분리한 연구가 확보되면 그 질문을 별도로 다시 평가한다. ASCENT03의 사전 계획된 전체 생존 수치가 보고되면 해당 비대상 집단 판단을 별도로 갱신한다." }, { "id": "QP-34", "kind": "Judgment held pending evidence", "text": "유지치료의 진행 지연을 재발 예방과 구분", "need": "같은 시험의 성숙한 전체 생존과 중추신경계 결과·비교 안전성이 공개되면 판단을 갱신한다. 도입치료를 포함한 전체 전략이나 수술 후 재발 예방으로 범위를 넓히려면 해당 질문의 직접 비교가 필요하다." }, { "id": "QP-35", "kind": "Judgment held pending evidence", "text": "진행 뒤 약제 유지와 교체는 별개다", "need": "이전 약제와 진행 시점이 같은 집단에서 유지·교체 전략을 직접 비교하거나, 사전에 정한 하위군과 상호작용이 독립적으로 확인되면 해당 범위의 판단을 갱신한다. 성숙한 전체 생존과 비교 안전성 자료는 무진행생존 결과와 별도로 평가한다." }, { "id": "QP-36", "kind": "Judgment held pending evidence", "text": "표적이 같아도 수술 뒤 조건은 다르다", "need": "같은 이전 치료와 위험 조건에서 전략을 직접 비교한 결과가 공개되면 관계를 다시 판단한다. 새로운 치료를 거친 환자에게 확장하려면 그 치료 이력이 포함된 근거가 필요하며, 시험 간 단순 수치 비교만으로는 판단을 바꾸지 않는다." }, { "id": "QP-37", "kind": "Judgment held pending evidence", "text": "치료 축소는 무엇을 줄였는지부터 확인", "need": "대상군과 이전 치료를 맞추고 축소할 요소를 명확히 한 직접 비교에서 사전 비열등성 경계, 충분한 추적과 위해 평가가 함께 충족되면 그 조건에 한해 판단을 넓힌다. 전체군 검정 실패를 탐색 하위군이나 생존율의 단순 유사성만으로 바꾸지는 않는다." }, { "id": "QP-40", "kind": "Judgment held pending evidence", "text": "재발 위험 점수와 항암 이득은 다르다", "need": "같은 림프절·폐경·점수 조건에서 사전에 정한 표지자와 치료의 상호작용 및 표지자 기반 전략의 환자 결과가 독립적으로 확인되면 적용 범위를 갱신한다. 젊은 집단의 기전을 구분하려면 난소기능 억제와 항암 기여를 직접 평가한 비교 근거가 필요하다." }, { "id": "QP-42", "kind": "Judgment held pending evidence", "text": "수술 뒤 면역치료 생략은 아직 미결", "need": "수술 전 치료와 수술 후 배정 시점이 명확하고, 생략의 허용 손실·통계 검정·장기 추적·중증 위해를 미리 정한 무작위 비교가 확보되면 판단을 갱신한다. 현재 관찰연구의 전문과 시간 기준·매칭 변수부터 확인한다." }, { "id": "QP-43", "kind": "Judgment held pending evidence", "text": "변이군의 진행 지연과 약제 순위는 별개", "need": "변이 여부에 따른 치료 상호작용, 전체 생존과 중증 위해, 동등한 치료 맥락의 직접 비교가 검토되면 선별 범위와 치료 순서 가설을 갱신한다. 전체 이상반응 빈도가 비슷하다는 이유만으로 안전성 동등성을 인정하지 않는다." }, { "id": "QP-44", "kind": "Judgment held pending evidence", "text": "혈액 신호가 없어도 남는 직장암 절제 판단", "need": "검사 기준과 채혈 시점이 고정된 독립 집단에서 임상·영상·병리 평가에 추가되는 가치가 확인되고, 검사에 따른 개입 전략이 재발과 장기 기능을 비교한 결과가 나오면 생략 가설을 다시 검토한다." }, { "id": "QP-45", "kind": "Judgment held pending evidence", "text": "핵으로 옮겨간 단백질과 내성 가설의 거리", "need": "자연적으로 핵 내 축적이 높은 독립 모형에서 상호작용의 필요성과 약제 반응이 재현되고, 환자 선별 기준 및 비교 임상 결과가 확보되면 치료 가설의 준비도를 다시 평가한다." }, { "id": "QP-46", "kind": "Judgment held pending evidence", "text": "간 전이 절제 후 조직검사로 읽는 재발 위험", "need": "독립 집단의 예측 성능과 검사 기반 개입의 비교 결과가 확보되면 치료 선택 가설을 다시 평가한다." }, { "id": "QP-47", "kind": "Judgment held pending evidence", "text": "손상 소기관 청소가 항암제 내성을 돕는 조건", "need": "표적 선택성과 독립 모형의 재현, 노출·안전성 및 비교 임상 결과가 확보되면 치료 가설의 준비도를 다시 평가한다." }, { "id": "QP-48", "kind": "Judgment held pending evidence", "text": "소엽암의 아형별 위험 차이는 아직 미결", "need": "충분한 표본의 독립 연구에서 교호작용과 추적 지표가 사전 계획대로 재현되면 다시 판단한다." }, { "id": "QP-49", "kind": "Judgment held pending evidence", "text": "증식 지표의 변화와 수술 선택은 별개다", "need": "측정 기준을 고정한 독립 검증과 검사 기반 수술 전략의 비교 결과가 확보되면 다시 평가한다." }, { "id": "QP-50", "kind": "Judgment held pending evidence", "text": "면역항암 이득은 검사 점수 구간에 한정한다", "need": "점수가 낮은 구간을 사전에 주분석으로 정한 무작위 시험에서 생존 이득이 확인되면 범위를 다시 정한다." }, { "id": "QP-51", "kind": "Judgment held pending evidence", "text": "대장암 HER2 표적 반응은 대조 없이 못 정함", "need": "HER2 양성 대장암에서 표준치료와 비교한 무작위 시험의 생존 결과가 공개되거나 저발현 환자를 충분히 포함한 결과가 나오면 다시 판단한다." }, { "id": "QP-52", "kind": "Judgment held pending evidence", "text": "같은 계열 약의 생존 성적을 서로 빌리지 않음", "need": "같은 계열 약을 직접 비교한 무작위 시험이나 환자 수준 자료를 맞춘 비교에서 일관된 생존 결과가 나오면 다시 판단한다." }, { "id": "QP-53", "kind": "Judgment held pending evidence", "text": "갑상선염이 암을 부르는지 막는지는 미정", "need": "갑상선염 진단 시점과 이후 갑상선 검사 횟수를 기록한 인구 기반 자료에서, 검사 강도를 맞춘 뒤에도 발생 차이가 남거나 같은 병기 안에서 사망 차이가 남으면 해당 방향의 판단을 다시 쓴다." }, { "id": "QP-54", "kind": "Judgment held pending evidence", "text": "암으로 가지 않는 조건은 아직 정해지지 않음", "need": "검사 강도를 맞춘 장기 추적에서 결절이 없거나 항체가 낮은 환자군의 암 발생이 대조군과 같다고 확인되면, 그 범위에서 조건을 기록한다. 반대로 결절이 없던 환자에서 암이 반복해 보고되면 두 번째 관찰을 고친다." }, { "id": "QP-55", "kind": "Judgment held pending evidence", "text": "호르몬 수치 조절과 종양 예방은 다른 문제", "need": "호르몬 치료 여부를 무작위로 나누거나 치료 시작 시점과 검사 강도를 맞춘 추적 연구에서 암 발생 차이가 확인되면 다시 판단한다." }, { "id": "QP-56", "kind": "Judgment held pending evidence", "text": "어린 환자의 결절은 성인 자료로 못 읽음", "need": "갑상선염 진단 시점부터 결절 발생과 암 진단을 차례로 기록한 소아 전향 자료가 나오면 결절 환자와 전체 환자의 위험을 나누어 다시 쓴다." }, { "id": "QP-57", "kind": "Judgment held pending evidence", "text": "증상 없는 환자의 정기 초음파 이득은 미확인", "need": "진찰이 정상인 갑상선염 환자를 정기 초음파군과 진찰 중심 추적군으로 나누어 병기, 치료 범위, 재발을 비교한 자료가 나오면 다시 판단한다." }, { "id": "QP-58", "kind": "Judgment held pending evidence", "text": "추적 자료의 서로 다른 발생 비율은 합치지 않음", "need": "같은 기준으로 모은 갑상선염 환아와 대조군을 같은 간격의 초음파로 추적한 자료가 나오면 그 수치를 기준으로 다시 쓴다." }, { "id": "QP-59", "kind": "Judgment held pending evidence", "text": "직장암 수술 보류의 안전성은 무작위 비교가 없다", "need": "경과 관찰과 즉시 수술을 무작위로 비교한 시험의 장기 생존과 원격 전이 결과가 공개되면 다시 판단한다." }, { "id": "QP-60", "kind": "Judgment held pending evidence", "text": "영상 반응으로 항암을 줄인 전략의 3년 성적", "need": "병리 반응에 따라 항암을 생략하는 전략을 표준 항암과 무작위로 비교한 결과가 나오거나, 이 시험의 5년 이상 추적에서 호르몬 수용체 양성 환자의 늦은 재발 자료가 나오면 다시 판단한다." }, { "id": "QP-61", "kind": "Judgment held pending evidence", "text": "보조 퍼투주맙의 생존 이득은 아직 확정 전", "need": "최종 전체 생존 분석이 공개되거나 림프절 음성 환자에서 재발 감소를 보인 독립 자료가 나오면 다시 판단한다." }, { "id": "QP-62", "kind": "Judgment held pending evidence", "text": "같은 검사법에서도 위암 공동증폭이 더 잦았다", "need": "무작위 시험의 치료군과 대조군 양쪽에서 CCNE1 공동증폭 여부에 따른 반응과 생존을 사전에 정한 방법으로 비교한 자료가 나오면 내성과의 관계를 다시 판단한다. 같은 검사법을 쓴 다른 코호트에서 방향이 뒤집히면 암종 차이 판단도 다시 본다." }, { "id": "QP-63", "kind": "Judgment held pending evidence", "text": "dMMR 결장암은 수술 전 항암 효과가 작게 보고됨", "need": "dMMR 결장암에서 수술 전 면역항암과 표준치료를 무작위로 비교한 시험의 무재발 생존이 공개되거나, FOxTROT 원문의 dMMR 하위군 수치와 교호작용 검정이 확인되면 다시 판단한다." }, { "id": "QP-64", "kind": "Judgment held pending evidence", "text": "호르몬 양성 조기 유방암의 면역치료는 병리 결과뿐", "need": "두 시험 가운데 하나라도 무사건 생존 결과를 공개하면 그 결과로 다시 판단한다. 이 아형에서 병리학적 완전반응과 장기 결과의 연관을 시험 수준에서 확인한 분석이 나와도 다시 본다." }, { "id": "QP-65", "kind": "Judgment held pending evidence", "text": "화학요법을 뺀 두 방식은 결과가 서로 달랐다", "need": "반응에 따라 화학요법을 생략하는 전략을 표준 치료와 무작위로 비교한 결과가 공개되면 다시 판단한다." }, { "id": "QP-66", "kind": "Judgment held pending evidence", "text": "위암 병리 반응 상승과 재발 감소는 따로 본다", "need": "병리 반응만 보고된 시험들의 무사건 생존 결과가 공개되거나, 위암에서 병리 반응과 생존의 연관을 시험 수준에서 확인한 통합 분석이 나오면 다시 판단한다." }, { "id": "QP-67", "kind": "Judgment held pending evidence", "text": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "need": "다른 기관의 충분히 큰 자료에서 사전에 정한 같은 비교가 지지되면 보류를 푼다. 수용체 아형과 치료 이력이 있는 자료에서 비교하면 A2의 원래 대상과도 맞춰 볼 수 있다." }, { "id": "QP-68", "kind": "Judgment held pending evidence", "text": "식도 접합부 보조 면역치료는 위암 근거가 아니다", "need": "수술 전 치료 뒤 잔존암이 있는 위암 환자에서 수술 뒤 항암에 면역항암제를 더하는 무작위 비교 결과가 공개되면 다시 판단한다. 항암을 면역항암제로 바꾼 비교는 이미 항암 쪽이 유리했다." }, { "id": "QP-69", "kind": "Judgment held pending evidence", "text": "혈액 검사의 앞선 경고와 치료 이득은 별개", "need": "검사 양성 환자를 무작위로 나눠 조기 치료와 관찰을 비교한 시험이 재발이나 생존의 개선을 보이면 그 암종과 치료에 한해 판단을 바꾼다." }, { "id": "QP-70", "kind": "Judgment held pending evidence", "text": "HER2 양성 병용의 재발 감소는 미확인", "need": "비교 가능한 HER2 양성 조기 집단에서 사전 지정한 생존 평가변수와 안전성의 이득이 충분한 사건 수를 갖춘 무작위 비교로 확인되면 범위를 갱신한다." }, { "id": "QP-71", "kind": "Judgment held pending evidence", "text": "관찰 비교의 시간 조건부터 검토함", "need": "치료 시작점·적격성·추적·달력 시기를 동시에 맞춘 분석과 미측정 교란 검토가 확보되고 독립 자료나 직접 무작위 비교에서 재현되면 판단을 갱신한다." }, { "id": "QP-72", "kind": "Judgment held pending evidence", "text": "낮은 점수의 해석은 림프절 범위에 달린다", "need": "같은 림프절 범위와 점수 정의에서 치료 시점을 맞춘 무작위 비교나 적절한 독립 인과 추론 자료가 재발·생존·위해를 함께 확인하면 적용 경계를 갱신한다." }, { "id": "QP-73", "kind": "Judgment held pending evidence", "text": "복구 경로가 같아도 내성 조건은 다르다", "need": "같은 약제·노출·유전 배경을 맞춘 비교와 복구 경로의 되살림 대조, 정상 조직 위해, 독립 검증이 나오면 공통 병용 후보의 범위를 다시 정한다." }, { "id": "QP-74", "kind": "Judgment held pending evidence", "text": "같은 유전자군도 억제 방향은 갈릴 수 있다", "need": "서로 다른 BRCA1·BRCA2 배경에서 선택적 조작과 되살림 대조가 재현되고 환자 유래 모형 및 적절한 임상 비교로 방향이 확인되면 적용 범위를 갱신한다." }, { "id": "QP-75", "kind": "Judgment held pending evidence", "text": "GDSC 예측과 치료 반응의 검증은 다르다", "need": "미리 고정한 모형이 독립된 옥살리플라틴 치료 코호트의 실제 반응에서 적절한 기준보다 개선되고 보정·오류·아형별 성능이 확인되면 환자 반응 예측 범위를 갱신한다." }, { "id": "QP-76", "kind": "Judgment held pending evidence", "text": "누적 간 위해는 보조·전이 치료를 나눠 읽음", "need": "치료 맥락과 관찰 시간을 맞춘 독립 코호트 및 적절한 대조에서 같은 사건 정의로 위해가 재현되고 시간 의존 분석과 교란 검토가 충분하면 해석 범위를 갱신한다." }, { "id": "QP-77", "kind": "Judgment held pending evidence", "text": "항체에 따라 점상 염색의 해석이 달라짐", "need": "표준화한 내부 대조와 맹검 판독, 다른 기관·항체의 재현, 적절한 분자 검사 대조가 갖춰지면 방법의 적용 범위를 다시 정한다. 치료 이득은 별도의 임상 비교가 필요하다." }, { "id": "QP-78", "kind": "Judgment held pending evidence", "text": "낮은 수용체 발현군의 생존 연관을 따져 봄", "need": "치료 시작과 추적 시작을 맞추고 누락·교란·시간 관련 오류를 검토한 자료에서 결과가 유지되며, 겹치지 않는 독립 자료 또는 적절한 전향 비교가 실제 치료 이득을 평가하면 범위를 갱신한다." }, { "id": "QP-79", "kind": "Judgment held pending evidence", "text": "엑손 조절과 환자 내성 극복은 분리함", "need": "동형과 엑손에 특이적인 조작 및 되살림 대조로 기여가 구분되고, 독립 모델에서 선택성·노출·위해와 지속 제어가 확인되면 전임상 범위를 갱신한다. 환자 치료 반응은 별도의 적절한 임상 검증이 필요하다." }, { "id": "QP-80", "kind": "Judgment held pending evidence", "text": "수질암 두 시험의 위험비는 나란히 못 놓음", "need": "두 약을 같은 선정 기준으로 무작위 비교한 결과가 공개되거나, 두 시험의 최종 전체 생존과 RET 변이별 결과가 원문에서 확인되면 다시 판단한다." }, { "id": "QP-81", "kind": "Judgment held pending evidence", "text": "지켜본 저위험 유두암의 결과는 범위가 좁다", "need": "관찰과 즉시 수술을 미리 정한 기준으로 비교한 전향 연구의 장기 결과가 공개되거나, 소아·청소년이나 갑상선염 동반 환자를 따로 추적한 관찰 자료가 나오면 범위를 다시 쓴다." }, { "id": "QP-82", "kind": "Judgment held pending evidence", "text": "선택적 RET 억제제끼리의 우열은 비교가 없다", "need": "두 약을 직접 비교한 자료나 프랄세티닙의 갑상선암 무작위 시험 결과가 공개되면 다시 판단한다." }, { "id": "QP-83", "kind": "Judgment held pending evidence", "text": "KRAS G12C 병용 효과는 고용량에서만 확인", "need": "이 시험의 최종 전체 생존이 공개되거나, KRAS 억제제 단독과 EGFR 항체 병용을 무작위로 비교한 결과가 나오면 다시 판단한다." }, { "id": "QP-84", "kind": "Judgment held pending evidence", "text": "후기 치료의 생존 이득은 크기를 함께 적는다", "need": "후기 치료끼리 직접 비교한 무작위 결과나, 삶의 질과 생존을 함께 본 분석이 공개되면 순서와 크기에 대한 기록을 다시 쓴다." }, { "id": "QP-85", "kind": "Judgment held pending evidence", "text": "보조 항암 기간 단축은 요법에 따라 갈린다", "need": "이 분석의 전체 생존 최종 보고와 신경 독성 수치를 원문에서 확인하거나, 요법을 무작위로 배정한 기간 비교가 공개되면 다시 판단한다." }, { "id": "QP-86", "kind": "Judgment held pending evidence", "text": "BRAF 변이 일차 치료의 생존은 중간 분석 단계", "need": "전체 생존의 최종 분석과 표적 병용 단독군의 결과가 공개되면 크기와 항암의 몫을 다시 쓴다." }, { "id": "QP-87", "kind": "Judgment held pending evidence", "text": "dMMR 3기 보조 면역항암의 이득은 재발 지표까지", "need": "이 시험의 전체 생존이 공개되거나, 수술 전 면역항암과 보조 병용을 무작위로 비교한 결과가 나오면 다시 판단한다." }, { "id": "QP-88", "kind": "Judgment held pending evidence", "text": "한 계열 세 약의 수명 연장 성적이 엇갈렸다", "need": "세 약을 직접 비교한 무작위 시험이 공개되거나, 개별 환자 자료로 대상과 추적을 맞춘 통합 분석이 공개되면 다시 판단한다." }, { "id": "QP-89", "kind": "Judgment held pending evidence", "text": "접합부암 수술 전 요법 비교는 시대가 어긋난다", "need": "수술 전후 항암과 항암방사선 뒤 면역항암제 전략을 직접 비교한 무작위 결과가 공개되거나, 니볼루맙 시험의 전체 생존 결과가 공개되면 다시 판단한다." }, { "id": "QP-90", "kind": "Judgment held pending evidence", "text": "진행만 늦춘 HER2 추가 약은 수명 이득 미정", "need": "투카티닙과 T-DM1 병용 시험의 최종 전체 생존이 공개되면 그 조합에 대한 판단을 다시 쓴다. 뇌 전이 환자에서 사전에 정한 평가변수의 결과가 수치로 보고되면 그 집단을 따로 판단한다." }, { "id": "QP-91", "kind": "Judgment held pending evidence", "text": "요오드 생략의 비열등성은 5년 지표까지 봄", "need": "두 시험의 더 긴 추적 결과가 공개되거나, 더 큰 종양이나 림프절 전이 환자만을 대상으로 한 무작위 비교가 나오면 범위를 다시 쓴다." }, { "id": "QP-92", "kind": "Judgment held pending evidence", "text": "관찰 코호트의 종양 증가 비율은 기준이 다르다", "need": "같은 측정 기준과 같은 추적 간격으로 여러 코호트를 합친 분석이나, 갑상선염 동반 환자의 수치를 따로 보고한 관찰 자료가 공개되면 다시 쓴다." }, { "id": "QP-94", "kind": "Judgment held pending evidence", "text": "같은 예측식도 사건에 따라 성능이 갈림", "need": "사건 정의·추적·경쟁 사건과 자료 겹침을 감사한 고정 모형을 적격 독립 자료에서 다시 평가하고, 사건별 보정·오분류·불확실성이 확인되면 예측 범위를 갱신한다. 검사 전략의 이득은 전향적인 적절한 비교가 따로 필요하다." }, { "id": "QP-95", "kind": "Judgment held pending evidence", "text": "위암의 락틸화 차단은 세포·동물 근거임", "need": "독립적인 위암 모형에서 변형 부위의 인과성과 기능 회복 실험이 확인되고, 임상에서 달성 가능한 노출과 정상 조직 위해·병용 상호작용을 검토하면 전임상 후보의 범위를 갱신한다. 환자 치료 이득은 적격 인간 비교 연구가 공개돼야 별도로 판단한다." }, { "id": "QP-96", "kind": "Judgment held pending evidence", "text": "효소의 재상승과 치료 선택 기준을 구분함", "need": "측정법과 채취 시점을 고정한 독립 자료에서 예후 인자와 치료 이력을 조정하고, 표지와 치료 효과의 상호작용이 확인되면 예측 표지의 범위를 갱신한다. 추가 억제의 임상 이득은 정상 조직 위해를 포함한 적격 비교 연구가 따로 필요하다." }, { "id": "QP-93", "kind": "Judgment held pending evidence", "text": "병리 판별력은 치료 성과와 따로 평가함", "need": "환자와 사전학습 자료의 겹침 및 정보 유입을 감사하고 고정한 모형을 독립 자료에서 재실행한 뒤, 보정·오분류·기준 모형 대비 차이가 확인되면 계산 검증 범위를 갱신한다. 치료 변경의 이득은 전향적인 적절한 비교가 따로 필요하다." }, { "id": "QP-97", "kind": "Judgment held pending evidence", "text": "전이의 변이 시점과 재발 차단은 별개", "need": "자료 선정과 전이·잠복기의 정의 및 변이 시점 추론을 감사하고, 고정한 경로와 모형을 별도 자료에서 평가해 불확실성과 대안 설명이 비교되면 관측 범위를 갱신한다. 재발 차단의 이득은 정상 조직 위해를 포함한 적격 개입 비교가 따로 필요하다." }, { "id": "QP-98", "kind": "Judgment held pending evidence", "text": "내성 병용의 음성 결과와 위해를 함께 읽음", "need": "원문에서 군별 추정과 불확실성·노출·위해를 대조하고, 독립적인 적격 비교가 미리 정한 대상과 지표에서 이득을 보이면 해당 범위의 판단을 갱신한다. 탐색 생검의 사후 선택만으로 보류를 해제하지 않는다." }, { "id": "QP-99", "kind": "Judgment held pending evidence", "text": "변이별 투약 지속기간은 비교 약효와 다름", "need": "원문의 환자·종양·투약 분모와 중단 이유·치료 이력·누락을 감사하고 독립 자료에서 고정한 변이와 지표의 관계가 재확인되면 관측 범위를 갱신한다. 약제 선택의 이득은 적격 비교와 치료 상호작용의 별도 검증이 필요하다." }, { "id": "QP-100", "kind": "Judgment held pending evidence", "text": "재발 상태별 예후를 보조치료 효과와 구별함", "need": "상태 전이와 기점·추적·결측·치료 시점을 감사하고 별도 자료에서 고정한 모형의 보정과 불확실성을 확인하면 관측 범위를 갱신한다. 치료 이득은 적절히 시간과 선택을 통제한 독립 비교가 필요하다." }, { "id": "QP-101", "kind": "Judgment held pending evidence", "text": "내성의 공간 신호와 병용 검증은 별개", "need": "독립 환자와 성립하는 면역 맥락의 모형에서 영역 선택·반복 병변·노출·위해를 고정해 재확인되면 실험 후보의 범위를 갱신한다. 인간 병용의 이득은 적격 비교에서 따로 판정한다." }, { "id": "QP-102", "kind": "Judgment held pending evidence", "text": "장기 면역치료 추적과 수술 생략의 간극", "need": "원문과 변경 이력에서 사건 정의·분모·추적·구제 수술 및 위해를 확인하고, 사전 기준을 고정한 장기 보존 전략의 적절한 비교 결과가 나오면 해당 범위의 판단을 갱신한다." }, { "id": "QP-103", "kind": "Judgment held pending evidence", "text": "미생물 제제의 반응 기여도는 아직 미정", "need": "실제 투여 구성과 반응·안전성 분모 및 장기 추적을 확인하고, 같은 배경 치료에서 제제의 추가 기여를 구분하는 적격 비교가 나오면 그 범위에서 갱신한다." }, { "id": "QP-104", "kind": "Judgment held pending evidence", "text": "잠재 재발 모형의 설명과 실측 사이", "need": "입력·기점·검열·선택과 적합 절차를 감사하고, 고정한 모형을 독립 자료에서 기준모형과 비교해 보정과 불확실성을 확인하면 예측의 적용 범위를 갱신한다. 생물학적 잠재량은 별도의 실제 측정과 대조해야 한다." }, { "id": "QP-105", "kind": "Judgment held pending evidence", "text": "뇌 도달 약제의 병용에서도 멈춘 반응", "need": "고정한 용량·노출 조건과 적격 집단에서 별도 임상 연구가 재현 가능한 반응과 위해를 보여 주면 적용 범위를 갱신한다. 검사 기반 치료 변경은 미리 정한 전략의 비교 이득을 따로 확인해야 한다." }, { "id": "QP-106", "kind": "Judgment held pending evidence", "text": "방사선 분할 단축을 지지하는 범위", "need": "잠근 분석계획의 한계와 근거, 제외 사유, 계획 준수 분석 및 장기 위해 감시를 확인하면 결과의 견고성과 적용 범위를 갱신한다. 생존 이득은 해당 평가변수의 별도 근거가 필요하다." }, { "id": "QP-107", "kind": "Judgment held pending evidence", "text": "긴 추적이 남겨도 해결되지 않는 비교", "need": "원 등록·이전 보고·고정 계획의 평가변수와 분모를 대조하고 적절한 비교 연구가 해당 치료 과정의 이득과 위해를 검증하면 판단 범위를 갱신한다. 수술 후 예후 인자의 치료 전 선택 능력도 별도로 평가해야 한다." }, { "id": "QP-108", "kind": "Judgment held pending evidence", "text": "PI3K 변이 대장암의 아스피린 이득은 재발까지", "need": "전체 생존 결과나 같은 설계의 다른 시험 결과가 공개되거나, 변이가 없는 환자를 무작위 배정한 결과가 나오면 다시 판단한다." }, { "id": "QP-109", "kind": "Judgment held pending evidence", "text": "운동 프로그램의 생존 연장은 한 시험의 결과", "need": "다른 나라에서 같은 질문의 무작위 결과가 나오거나, 운동량에 따른 결과 차이를 보고한 원문 분석이 확인되면 범위를 다시 쓴다." }, { "id": "QP-110", "kind": "Judgment held pending evidence", "text": "pMMR 대장암 면역 병용은 시험마다 엇갈린다", "need": "일차 치료 병용의 3상 결과가 공개되거나, 2상의 pMMR 하위군 수치가 확인되면 다시 판단한다." }, { "id": "QP-111", "kind": "Judgment held pending evidence", "text": "렌바티닙 시작 용량을 낮추면 반응이 줄었다", "need": "두 시작 용량의 무진행 생존이나 전체 생존을 비교한 결과가 공개되면 다시 판단한다." }, { "id": "QP-112", "kind": "Judgment held pending evidence", "text": "중국 시험의 표적 억제제 결과는 대상 안에서", "need": "약끼리 직접 비교한 무작위 시험이나 개별 환자 자료를 합친 분석이 공개되면 다시 판단한다." }, { "id": "QP-113", "kind": "Judgment held pending evidence", "text": "미세한 폐 소견과 약제 위해의 연결", "need": "판독과 위해 판정 방법을 감사하고 별도 자료에서 보정된 절대 위험과 불확실성을 재현하면 예측 범위를 갱신한다. 그에 따른 치료·감시 전략의 이득과 위해는 별도 비교가 필요하다." }, { "id": "QP-114", "kind": "Judgment held pending evidence", "text": "호산구의 재발 연관성과 치료 선택 사이", "need": "원 방법에서 치료 배정·노출 시점·환자 중복·고정 기준과 상호작용을 확인하고, 별도 평가에서 치료별 이득과 위해를 검증하면 선택 능력의 적용 범위를 갱신한다." }, { "id": "QP-115", "kind": "Judgment held pending evidence", "text": "배양 반응 점수를 환자 확률로 옮기지 않음", "need": "원 입력·코드와 노출 조건을 대조해 고정한 점수를 재현하고, 독립 환자에서 사전에 정한 임상 결과와 보정·의사결정 이득을 검증하면 적용 범위를 갱신한다. 치료 축소의 안전성은 적절한 비교 연구가 필요하다." }, { "id": "QP-116", "kind": "Judgment held pending evidence", "text": "실질 뇌전이와 연수막 신호를 나눠 읽음", "need": "원 방법에서 코호트별 적격성·평가가능 분모·반응 확인·생존 단위·위해를 대조하고 적절한 별도 임상 평가에서 이득과 위해가 재현되면 해당 구획의 판단을 갱신한다." }, { "id": "QP-117", "kind": "Judgment held pending evidence", "text": "완전반응 뒤 유지 치료와 관찰의 간격", "need": "고정한 반응 판정과 치료 기점·추적 계획을 적용한 전향적 비교에서 원발 부위별 재성장·원격 재발·구제 실패와 위해의 불확실성이 충분히 좁아지면 생략 전략의 적용 범위를 갱신한다." }, { "id": "QP-118", "kind": "Judgment held pending evidence", "text": "복막 전이의 지방 이용을 끊는 가설", "need": "원 방법과 구제 실험에서 경로 특이성을 확인하고, 별도 모델에서 도달 가능한 약물 노출로 형성된 전이의 부담과 위해를 재현하면 다음 실험 후보의 범위를 갱신한다. 사람의 이득은 별도 임상 검증이 필요하다." }, { "id": "QP-119", "kind": "Judgment held pending evidence", "text": "잔존 병변의 HER2 불일치를 읽는 범위", "need": "처음 일치한 사례까지 포함한 표준화·눈가림 재판독에서 변화가 재현되고, 고정한 잔존 질환 집단의 전향적 비교에서 재평가에 따른 치료의 이득과 위해가 확인되면 적용 범위를 갱신한다." }, { "id": "QP-120", "kind": "Judgment held pending evidence", "text": "국소 면역 자극의 중단을 기록하는 기준", "need": "원 프로토콜과 정정에서 평가변수·분모·투약 변경과 위해 판정이 정리되고, 별도 연구에서 노출·전달·정상 조직 위해를 사전에 정한 기준으로 검증하면 다음 후보 범위를 갱신한다. 현재 시험의 실패 기록은 보존한다." }, { "id": "QP-121", "kind": "Judgment held pending evidence", "text": "수술을 포함한 무재발과 완치의 경계", "need": "추적 대상·위험집단 수·중도절단·확률 구간 계산과 프로토콜을 확인해 장기 판단을 갱신한다. 수술이나 추가 처치를 생략하는 전략은 그에 맞는 전향적 비교와 구제 실패·위해 확인이 있어야 별도로 평가한다." }, { "id": "QP-122", "kind": "Judgment held pending evidence", "text": "일차 항EGFR 항체의 생존 이득은 시험마다 다르다", "need": "세 시험의 RAS 확장 검사와 종양 위치별 개별 환자 자료 분석이 공개되면 범위를 다시 쓴다." }, { "id": "QP-123", "kind": "Judgment held pending evidence", "text": "강화 요법이 늘린 지표와 생존은 따로 본다", "need": "간 전이 절제 뒤 보조 항암의 생존을 다시 본 장기 추적이나 다른 무작위 시험 결과가 공개되면 다시 판단한다." }, { "id": "QP-124", "kind": "Judgment held pending evidence", "text": "분화암에서 MEK 억제제 추가 이득은 미확인", "need": "더 큰 무작위 비교나 무진행 생존을 비교한 결과가 공개되면 다시 판단한다." }, { "id": "QP-130", "kind": "Judgment held pending evidence", "text": "잔존 종양 부담 지표가 보여주는 범위", "need": "사전 계획과 개정 이력으로 등록 차이가 설명되고 생존 분석의 방향·정밀도 및 신경독성의 빈도·회복 경과가 확인되면 판단을 갱신한다." }, { "id": "QP-131", "kind": "Judgment held pending evidence", "text": "복막 전이의 잔존 신호를 읽는 조건", "need": "같은 채혈 기준과 분석 기점을 적용한 독립 자료에서 재현하고, 검사에 따른 개입을 비교한 연구에서 위해를 포함한 결과 개선을 확인하면 판단을 갱신한다." }, { "id": "QP-132", "kind": "Judgment held pending evidence", "text": "오래 반응한 유방암에서 음성 검사의 범위", "need": "같은 검사 일정과 영상 기준으로 치료 지속과 축소를 비교하고 장기 진행과 위해를 평가한 결과가 공개되면 판단을 갱신한다." }, { "id": "QP-133", "kind": "Judgment held pending evidence", "text": "수술 병리와 비수술 추적을 합친 반응률", "need": "같은 항암과 방사선치료를 비교군에 적용한 무작위시험에서 장기 직장 보존, 재발, 중증 위해를 함께 보고하면 판단을 갱신한다." }, { "id": "QP-134", "kind": "Judgment held pending evidence", "text": "허투에 따라 나뉜 치료군의 비교 한계", "need": "같은 허투 상태와 치료 조건에서 비교약을 무작위 배정하고 사건 수와 추적 기간을 공개하면 치료 효과를 다시 판단한다." }, { "id": "D-GENIE", "kind": "Dataset not connected", "text": "AACR Project GENIE", "need": "Project access approval and verified data acquisition are not documented in this library. The account and current terms-of-access requirements must be met, or shown to have been met, before a pinned release is connected." }, { "id": "HER2-HR+-0", "kind": "Empty cell in the HER2 level matrix", "text": "HR+ · IHC 0 no staining", "need": "No curated evidence for this combination." }, { "id": "HER2-HR−-0", "kind": "Empty cell in the HER2 level matrix", "text": "HR− · IHC 0 no staining", "need": "No curated evidence for this combination." }, { "id": "HER2-HR−-ultra", "kind": "Empty cell in the HER2 level matrix", "text": "HR− · IHC 0+ membrane staining (ultralow)", "need": "No curated evidence for this combination." } ], "replication": [ { "pair": "QP-01", "title": "유방암 HER2 근거를 위암에 어디까지 쓸 것인가", "claim": "자체 분석 A1에서는 ERBB2 증폭군의 공동증폭 비율이 위암 46.6% 대 유방암 7.3%였다. 별도 위암 자료의 CV-A1은 같은 방향을 지지했지만, 새로운 EGC-MSK 위암 자료의 CV-A3은 3/26 대 재사용 METABRIC 비교군 42/298로 판단 불가였다. 두 외부 평가는 유방암 비교군을 공유하며 측정 플랫폼과 암종의 영향을 분리하지 못하므로, 암종 전체의 보편적 차이나 치료 반응으로 확대하지 않는다.", "units": [ "U-A1" ] }, { "pair": "QP-05", "title": "새 분석과 재현 중 무엇을 먼저 할 것인가", "claim": "자체 분석 A1과 A3의 계산 재현은 완료됐다. 이는 고정 입력과 계산 결과를 확인한 기록이며 별도 환자군의 생물학적 결과를 새로 확인한 것은 아니다.", "units": [ "U-A1", "U-A3" ] }, { "pair": "QP-05", "title": "새 분석과 재현 중 무엇을 먼저 할 것인가", "claim": "A1의 별도 위암·유방암 코호트 평가는 공동증폭의 비교 방향을 지지했다. 위암의 증폭군이 작고 측정 플랫폼이 달라 치료 반응이나 인과 기전까지 입증하지는 못했다.", "units": [ "U-A1" ] }, { "pair": "QP-05", "title": "새 분석과 재현 중 무엇을 먼저 할 것인가", "claim": "A2의 외부 코호트 평가는 판단 불가였고, A5는 같은 수집 자료에 적용한 새로운 짝지은 관찰 분석이다. 이를 독립 검증 성공으로 합산하지 않는다.", "units": [ "U-A2", "U-A5" ] }, { "pair": "QP-08", "title": "진행 전 교체의 이득을 무엇으로 셀 것인가", "claim": "환자를 짝짓지 않고 원발·전이 표본군을 비교한 A2와 같은 환자의 검체를 짝지은 A5는 검출 양상의 관찰이다. 선택한 검체의 순서와 치료 노출이 달라 변이의 획득이나 치료 효과를 직접 검증하지 않았다.", "units": [ "U-A2", "U-A5" ] }, { "pair": "QP-08", "title": "진행 전 교체의 이득을 무엇으로 셀 것인가", "claim": "A2의 별도 수집 코호트 평가는 같은 방향의 점추정치를 보였지만 불확실성 때문에 판단 불가로 남았다. 혈액을 이용한 치료 교체 시험과 조직 검체의 비교는 같은 평가변수가 아니다.", "units": [ "U-A2" ] }, { "pair": "QP-13", "title": "동형을 가리지 않은 예측 모델은 쓰지 않음", "claim": "자체 분석 A3에서 두 동형은 길이가 같고 차이는 모두 1–69번 구간 안에 있으며 70번부터 같다. 정형 동형의 위상 주석에 따르면 1–69번 구간은 N-말단 세포질 분절(1–6번), 첫 막관통 나선(7–27번), 첫 세포외 영역(28–80번)의 대부분에 걸친다. 이 주석이 다른 동형에서도 유지되는지는 해당 계산으로 확인하지 않았다.", "units": [ "U-A3" ] }, { "pair": "QP-14", "title": "재발과 전이를 반응 연구와 떼어 관리하는가", "claim": "서로 다른 환자의 원발·전이 검체를 비교한 계산에서는 수용체 유전자 변이 빈도가 달랐다. 이 관찰과 치료 노출에 따른 유전체 연관만으로 개별 환자에게 변이가 생긴 원인이나 재발 예방 전략의 효과를 확정할 수는 없다.", "units": [ "U-A2", "U-Razavi18" ] }, { "pair": "QP-16", "title": "항체 기능으로 동형 판별을 대신하지 않음", "claim": "저장된 서열 비교에서는 클라우딘18의 두 동형 사이에 차이가 확인됐다. 해당 계산은 서열 비교이며 항체 결합이나 임상 검사 일치율을 측정한 자료가 아니다.", "units": [ "U-A3" ] }, { "pair": "QP-62", "title": "같은 검사법에서도 위암 공동증폭이 더 잦았다", "claim": "자체 분석 A1에서는 위암 46.6% 대 유방암 7.3%였다. 측정법이 암종마다 달랐던 첫 외부 평가는 같은 방향을 지지했고, 다른 위암 자료를 쓴 평가는 판단 불가였다.", "units": [ "U-A1" ] }, { "pair": "QP-62", "title": "같은 검사법에서도 위암 공동증폭이 더 잦았다", "claim": "중국 범암종 자료를 쓴 외부 평가(CV-A1-OM)는 두 암종을 같은 패널로 측정해 측정법 차이를 없앴다. 차이는 27.1%포인트, 95% 구간은 11.5에서 40.7이었다. 이 결과는 근거 단위가 아니라 코호트 평가 기록으로 보관한다.", "units": [ "U-A1" ] }, { "pair": "QP-67", "title": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "claim": "자체 분석 A2는 2018년 자료의 호르몬 수용체 양성·HER2 음성 표본에서 전이 19.2% 대 원발 2.6%를 보고했고, 같은 환자의 짝 검체를 본 A5도 같은 방향이었다.", "units": [ "U-A2", "U-A5" ] }, { "pair": "QP-67", "title": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "claim": "같은 병원의 2025·2026년 자료에서 기존 자료의 환자를 환자번호로 뺀 4,132명을 평가한 결과(CV-A2-MSK)는 전이 278/2,352 대 원발 22/1,780이었다. 기관·검사법·판정 과정이 A2와 같아 코호트 평가 기록에 외부 코호트가 아니라고 표시했다.", "units": [ "U-A2" ] }, { "pair": "QP-67", "title": "ESR1 양상의 재확인은 같은 병원 안에 머문다", "claim": "다른 기관 자료를 쓴 두 평가(CV-A2, CV-A5)는 표본과 검출 사건이 적어 판단 불가였다. 이 평가들은 근거 단위가 아니라 코호트 평가 기록으로 보관한다.", "units": [ "U-A2", "U-A5" ] } ], "contradictions": [ { "q": "Adjuvant CDK4/6 inhibition in HR+/HER2− early breast cancer", "a": [ "U-monarchE", "U-NATALEE" ], "b": [ "U-PALLAS", "U-PENELOPEB" ], "differs": [ "Agent", "Population risk definition", "Endocrine backbone", "Analysis timing" ], "pair": "QP-04" }, { "q": "Atezolizumab in advanced triple-negative breast cancer", "a": [ "U-IMP130" ], "b": [ "U-IMP131" ], "differs": [ "Companion chemotherapy", "PD-L1 assay population", "Endpoint assessment" ], "pair": "QP-03" }, { "q": "Anti-HER2 agents beyond trastuzumab in gastric cancer", "a": [ "U-DG01", "U-DG04", "U-HERIZON" ], "b": [ "U-GATSBY", "U-JACOB", "U-LOGiC", "U-TyTAN" ], "differs": [ "Delivery format", "Line of therapy", "HER2 re-confirmation", "Comparator" ], "pair": "QP-01" }, { "q": "PD-1 blockade by line in gastric cancer", "a": [ "U-CM649", "U-KN859" ], "b": [ "U-KN061", "U-KN062" ], "differs": [ "Line", "Monotherapy vs combination", "CPS cut-off", "Comparator" ], "pair": "QP-03" } ], "nextActions": [ { "area": "RK-O", "gap": "No citable record of our own analyses", "action": "Publish A1–A3 scripts and derived tables with a licence and a DOI", "unlocks": "runs an open resource this draft queries", "effort": "days" }, { "area": "RK-S", "gap": "Every structural statement is read from a database", "action": "Produce the contact-residue map requested in SD-CLDN18 from 9V32", "unlocks": "structural or computational method papers 2021–2025", "effort": "weeks, needs structure-handling tooling" }, { "area": "RK-G", "gap": "A1 external evaluations: three supported and one inconclusive; two of them (CV-A1-20260930, CV-A3) share the METABRIC comparator", "gapKo": "A1 외부 평가는 지지 3건·판단 불가 1건이며, 그중 2건(CV-A1-20260930, CV-A3)이 METABRIC 비교군을 공유함", "action": "Before any further comparison, confirm that CNA measurement and patient selection are comparable; account for the reused comparator, wide intervals and missing treatment data", "actionKo": "추가 비교 전에 CNA 측정과 환자 선별의 비교 가능성을 확인하고, 재사용 비교군·넓은 구간·치료 자료 부재를 반영한다", "unlocks": "precision and scope of the observation", "effort": "requires suitable metadata and an analysis plan" }, { "area": "RK-B", "gap": "A2 external cohort evaluations: one supported (CV-A2-MSK-20261007) and one inconclusive (CV-A2-20260930)", "gapKo": "A2 외부 코호트 평가는 지지 1건(CV-A2-MSK-20261007)·판단 불가 1건(CV-A2-20260930)", "action": "Find a further separate cohort with compatible specimen definitions and ESR1 coverage, fixing selection rules before molecular outcomes", "actionKo": "검체 정의와 ESR1 검사 범위가 비교 가능한 또 다른 별도 코호트를 찾고 분자 결과를 보기 전에 선별 규칙을 고정한다", "unlocks": "precision and scope of the observation", "effort": "requires suitable metadata and an analysis plan" }, { "area": "RK-T", "gap": "No laboratory or clinical arm", "action": "Not reachable alone; requires collaboration", "unlocks": "nothing yet", "effort": "not scheduled" }, { "area": "RK-O", "gap": "QP-01: scope of the A1 evidence", "gapKo": "QP-01: A1 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: CV-A1-20260930: direction supported; CV-A3: inconclusive; CV-A1-OM-20261006: direction supported; CV-A1-MSK50K-20261022: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: CV-A1-20260930: 방향 지지; CV-A3: 판단 불가; CV-A1-OM-20261006: 방향 지지; CV-A1-MSK50K-20261022: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-05: scope of the A1 evidence", "gapKo": "QP-05: A1 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: CV-A1-20260930: direction supported; CV-A3: inconclusive; CV-A1-OM-20261006: direction supported; CV-A1-MSK50K-20261022: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: CV-A1-20260930: 방향 지지; CV-A3: 판단 불가; CV-A1-OM-20261006: 방향 지지; CV-A1-MSK50K-20261022: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-05: scope of the A3 evidence", "gapKo": "QP-05: A3 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: not recorded. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: 기록 없음. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-05: scope of the A2 evidence", "gapKo": "QP-05: A2 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A2-20260930: inconclusive; CV-A2-MSK-20261007: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A2-20260930: 판단 불가; CV-A2-MSK-20261007: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-05: scope of the A5 evidence", "gapKo": "QP-05: A5 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A5-20261005: inconclusive. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A5-20261005: 판단 불가. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-08: scope of the A2 evidence", "gapKo": "QP-08: A2 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A2-20260930: inconclusive; CV-A2-MSK-20261007: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A2-20260930: 판단 불가; CV-A2-MSK-20261007: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-08: scope of the A5 evidence", "gapKo": "QP-08: A5 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A5-20261005: inconclusive. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A5-20261005: 판단 불가. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-13: scope of the A3 evidence", "gapKo": "QP-13: A3 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: not recorded. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: 기록 없음. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-14: scope of the A2 evidence", "gapKo": "QP-14: A2 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A2-20260930: inconclusive; CV-A2-MSK-20261007: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A2-20260930: 판단 불가; CV-A2-MSK-20261007: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-16: scope of the A3 evidence", "gapKo": "QP-16: A3 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: not recorded. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: 기록 없음. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-62: scope of the A1 evidence", "gapKo": "QP-62: A1 근거의 적용 범위", "action": "Computational reproduction: completed. External cohort evaluation: CV-A1-20260930: direction supported; CV-A3: inconclusive; CV-A1-OM-20261006: direction supported; CV-A1-MSK50K-20261022: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 완료. 외부 코호트 평가: CV-A1-20260930: 방향 지지; CV-A3: 판단 불가; CV-A1-OM-20261006: 방향 지지; CV-A1-MSK50K-20261022: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-67: scope of the A2 evidence", "gapKo": "QP-67: A2 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A2-20260930: inconclusive; CV-A2-MSK-20261007: direction supported. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A2-20260930: 판단 불가; CV-A2-MSK-20261007: 방향 지지. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" }, { "area": "RK-O", "gap": "QP-67: scope of the A5 evidence", "gapKo": "QP-67: A5 근거의 적용 범위", "action": "Computational reproduction: not recorded. External cohort evaluation: CV-A5-20261005: inconclusive. Check whether the recorded endpoint supports this judgment; address remaining population and measurement limits.", "actionKo": "계산 재현: 기록 없음. 외부 코호트 평가: CV-A5-20261005: 판단 불가. 기록된 평가변수가 이 판단을 뒷받침하는지 확인하고, 남은 모집단·측정 한계를 보완한다.", "unlocks": "scope of this judgment", "effort": "unscheduled" } ] }, "integrity": { "retrieved": "2026-11-13", "papersChecked": 1314, "duplicatePmids": [], "flagged": { "17192538": { "types": [], "refs": [], "notices": [ { "type": "ErratumIn", "pmid": null, "refSource": "N Engl J Med. 2007 Apr 5;356(14):1487" } ] }, "17978289": { "types": [], "refs": [], "notices": [ { "type": "ErratumIn", "pmid": null, "refSource": "N Engl J Med. 2008 May 1;358(18):1977" } ] }, "18364505": { "types": [], "refs": [], "notices": [ { "type": "ErratumIn", "pmid": null, "refSource": "J Natl Cancer Inst. 2008 May 7;100(9):685" } ] }, "20728210": { "types": [], "refs": [], "notices": [ { "type": "ErratumIn", "pmid": null, "refSource": "Lancet. 2010 Oct 16;376(9749):1302" } ] }, 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Assessment is limited to the existing evidence-unit claim and the correction scope. Corrected figures, tables, appendices and patient-level data were not independently audited.", "summary": "A missing footnote in Table 3 reports grade-4 adverse events: 13 events among 10 combination-arm patients and 16 events among 11 capecitabine-only patients. The notice describes the between-arm differences as not statistically significant and states that the table was corrected online. The correction concerns the adverse-event table and does not amend the initial time-to-progression estimates cited in the unit. The later final-OS paper is outside this notice and was not reaudited in this review. The current limits still incorrectly say the complete notice remains unread. Replace only the stale full-notice review-status passage; retain the early-stopping, crossover, toxicity and historical-comparator limitations. The corrected footnote is not evidence of equivalence or absence of toxicity and its event counts are not added to the abstract-only efficacy claim." } }, { "type": "ErratumIn", "pmid": null, "refSource": "N Engl J Med. 2008 May 1;358(18):1977", "forPmid": "17978289", "forKey": "P-ACTSGC07", "title": "N Engl J Med. 2008 May 1;358(18):1977", "text": "", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070056", "unresolvedIdentifier": true, "reviewed": true, "noticeSourceUrl": "https://pubmed.ncbi.nlm.nih.gov/17978289/", "review": { "pmid": null, "forPmid": "17978289", "type": "ErratumIn", "refSource": "N Engl J Med. 2008 May 1;358(18):1977", "doi": "10.1056/NEJMx070056", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx070056", "scope": "Full publisher correction read in browser and its original-article link matched. Original full article and patient data were not independently audited; PubMed notice PMID remains absent.", "summary": "The notice changes the third S-1 entry in Figure 1A from270to370. It does not amend the abstract efficacy or safety estimates used here. Original and five-year trial reports remain one evidence unit." } }, { "type": "ErratumIn", "pmid": null, "refSource": "J Natl Cancer Inst. 2008 May 7;100(9):685", "forPmid": "18364505", "forKey": "P-PM18364505", "title": "J Natl Cancer Inst. 2008 May 7;100(9):685", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/18364505/", "unresolvedIdentifier": true, "reviewed": false }, { "type": "ErratumIn", "pmid": null, "refSource": "Lancet. 2010 Oct 16;376(9749):1302", "forPmid": "20728210", "forKey": "P-ToGA", "title": "Lancet. 2010 Oct 16;376(9749):1302", "text": "", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61919-8/fulltext", "unresolvedIdentifier": true, "reviewed": true, "noticeSourceUrl": "https://pubmed.ncbi.nlm.nih.gov/20728210/", "review": { "pmid": null, "forPmid": "20728210", "type": "ErratumIn", "refSource": "Lancet. 2010 Oct 16;376(9749):1302", "doi": "10.1016/S0140-6736(10)61919-8", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61919-8/fulltext", "scope": "Complete official correction, linked original DOI and current publisher abstract were read. Assessment is limited to the existing overall-survival claim. The original full article, corrected figure and underlying patient data were not independently audited.", "summary": "The chemotherapy-arm median overall survival in Figure 4A must read 11.1 months. The notice states that the online correction was applied on October 8, 2010. The current unit already reports chemotherapy-arm median overall survival of 11.1 months. The current official publisher abstract also reports 13.8 versus 11.1 months and HR 0.74. The notice changes an efficacy figure value, but the existing unit already agrees with the corrected value." } }, { "type": "ErratumIn", "pmid": null, "refSource": "J Clin Oncol. 2013 Aug 20;31(24):3049", "forPmid": "22025146", "forKey": "P-T-ZETA12", "title": "J Clin Oncol. 2013 Aug 20;31(24):3049", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22025146/", "unresolvedIdentifier": true, "reviewed": false }, { "type": "ErratumIn", "pmid": null, "refSource": "Cancer Discov. 2012 Oct;2(10):960", "forPmid": "22588877", "forKey": "P-cBio", "title": "Cancer Discov. 2012 Oct;2(10):960", "text": "", "url": "https://aacrjournals.org/cancerdiscovery/article/2/10/960/2824/Correction-The-cBio-Cancer-Genomics-Portal-An-Open", "unresolvedIdentifier": true, "reviewed": true, "noticeSourceUrl": "https://pubmed.ncbi.nlm.nih.gov/22588877/", "review": { "pmid": null, "forPmid": "22588877", "type": "ErratumIn", "refSource": "Cancer Discov. 2012 Oct;2(10):960", "doi": "10.1158/2159-8290.CD-12-0326", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://aacrjournals.org/cancerdiscovery/article/2/10/960/2824/Correction-The-cBio-Cancer-Genomics-Portal-An-Open", "scope": "Complete official correction and its references linking original DOI and PMID were read. Review covers only the correction scope and current descriptive evidence claim. No genomic data, API output or source code were reevaluated.", "summary": "The Grant Support statement omitted the Starr Cancer Consortium funding, grant I5-A500, for the integration with Integrative Genomics Viewer (IGV). The correction adds funding attribution and does not amend the current description of the cancer-genomics platform. It does not establish or revalidate the local statement that IATHEON A1 and A2 use the API." } }, { "type": "ErratumIn", "pmid": null, "refSource": "N Engl J Med. 2013 Jun 20;368(25):2442", "forPmid": "23020162", "forKey": "P-EMILIA", "title": "N Engl J Med. 2013 Jun 20;368(25):2442", "text": "", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx130019", "unresolvedIdentifier": true, "reviewed": true, "noticeSourceUrl": "https://pubmed.ncbi.nlm.nih.gov/23020162/", "review": { "pmid": null, "forPmid": "23020162", "type": "ErratumIn", "refSource": "N Engl J Med. 2013 Jun 20;368(25):2442", "doi": "10.1056/NEJMx130019", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx130019", "scope": "Full official publisher correction read in Chrome and its linked original-article DOI matched to the saved PubMed record. Assessment is limited to the existing evidence-unit claim and the correction scope. Corrected figures, tables, appendices and patient-level data were not independently audited. The current official publisher abstract was also read and compared with the saved PubMed abstract.", "summary": "The aggregate adverse-event category must include grade 3 and all higher grades, rather than only grades 3 and 4. The correction applies to the Abstract Results, Results Safety paragraph, two Table 3 column headings and its second footnote. The current claim reports only independently reviewed PFS medians and a hazard ratio. These are unchanged in the current publisher abstract. The saved PubMed abstract retains superseded safety-category wording; preserving it without context risks later reusing an incorrect category. Preserve the raw PubMed source. Add the correction scope to limits and distinguish the aggregate grade-at-least-3 category from a grade-3-or-4-only category. No safety-equivalence claim or patient-level reanalysis follows from this review." } }, { "type": "ErratumIn", "pmid": null, "refSource": "Lancet. 2013 Mar 9;381(9869):804", "forPmid": "23219286", "forKey": "P-ATLAS", "title": "Lancet. 2013 Mar 9;381(9869):804", "text": "", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60252-4/fulltext", "unresolvedIdentifier": true, "reviewed": true, "noticeSourceUrl": "https://pubmed.ncbi.nlm.nih.gov/23219286/", "review": { "pmid": null, "forPmid": "23219286", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60252-4/fulltext", "sourceUrl": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3898894/", "scope": "Full official correction notice text read via indexed PMC result; no PMID is supplied by the notice. This is not an audit of patient-level data.", "summary": "Corrects the control cardiac-event count, transposes receptor-group labels in specified appendix plots, and restores omitted authors, collaborators and centers. The proposed unit omits the affected cardiac estimate and appendix curves; the reported ER-positive recurrence and breast-cancer mortality and selected noncardiac harms are outside the notice scope.", "refSource": "Lancet. 2013 Mar 9;381(9869):804", "doi": "10.1016/S0140-6736(13)60252-4" } }, { "type": "ErratumIn", "pmid": "28457627", "refSource": "Lancet. 2017 May 13;389(10082):1884. doi: 10.1016/S0140-6736(17)31004-8.", "forPmid": "23219286", "forKey": "P-ATLAS", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28457627/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "28457627", "forPmid": "23219286", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8889022/", "scope": "Full official correction notice read. The separate center-exclusion letter PMID 28457628 was identified but its full text was inaccessible and is not marked reviewed. No patient-level audit was performed.", "summary": "The audit update is limited in the main paper to ischemic heart disease, non-breast-cancer mortality, and mortality with unknown or any ER status. The proposed unit omits those estimates; ER-positive recurrence and breast-cancer mortality and selected noncardiac harms are outside the stated scope." } }, { "type": "ErratumIn", "pmid": null, "refSource": "Bioorg Med Chem Lett. 2013 Aug 15;23(16):4723", "forPmid": "23726034", "forKey": "P-BYL719", "title": "Bioorg Med Chem Lett. 2013 Aug 15;23(16):4723", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/23726034/", "unresolvedIdentifier": true, "reviewed": false }, { "type": "ErratumIn", "pmid": null, "refSource": "J Clin Oncol. 2014 Jun 10;32(17):1864", "forPmid": "24002501", "forKey": "P-T-EXAM13", "title": "J Clin Oncol. 2014 Jun 10;32(17):1864", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24002501/", "unresolvedIdentifier": true, "reviewed": false }, { "type": "ErratumIn", "pmid": "26559595", "refSource": "N Engl J Med. 2015 Nov 12;373(20):1989. doi: 10.1056/NEJMx150037.", "forPmid": "25564897", "forKey": "P-APT", "title": "Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26559595/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "26559595", "forPmid": "25564897", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx150037", "scope": "The web search tool returned the complete short correction text from the official NEJM page; direct open returned internal error. PubMed XML independently links this notice as ErratumIn. Original full article and patient-level data were not audited.", "summary": "In the Results adverse-events subsection, grade3 neuropathy during combination treatment was corrected from14 to13 patients (3.2%,95%CI1.7–5.4). The notice states the online article is corrected. Uses corrected13 and3.2%, matching the current official PubMed abstract. No efficacy result is identified as changed by this notice." } }, { "type": "ErratumIn", "pmid": "27760322", "refSource": "Cell Rep. 2016 Oct 18;17(4):1206. doi: 10.1016/j.celrep.2016.10.009.", "forPmid": "27149842", "forKey": "P-GiannakisCRC16", "title": "Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/27760322/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "27760322", "forPmid": "27149842", "type": "ErratumIn", "doi": "10.1016/j.celrep.2016.10.009", "reviewedAt": "2026-10-20", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5638785/", "scope": "Complete official short correction read in a visible browser on PubMed Central; original title and PubMed ErratumIn linkage verified. Review limited to the notice; whether the public portal data reflect the corrected table was not independently verified.", "summary": "Supplementary Table S3 was replaced with a version that includes all somatic mutations used in the analyses. No abstract value was changed. The library uses this study's public portal mutation data for analysis A8 and cites the paper only as the data source." } }, { "type": "ErratumIn", "pmid": "30586508", "refSource": "N Engl J Med. 2018 Dec 27;379(26):2582. doi: 10.1056/NEJMx180043.", "forPmid": "27717303", "forKey": "P-ML2", "title": "Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30586508/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "30586508", "forPmid": "27717303", "type": "ErratumIn", "doi": "10.1056/NEJMx180043", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx180043", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "The disclosure statement and disclosure forms were updated to add disclosures for three authors; the notice says the article is correct online. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "30894267", "refSource": "Lancet. 2019 Mar 16;393(10176):1100. doi: 10.1016/S0140-6736(18)32771-5.", "forPmid": "28215665", "forKey": "P-HERA11y", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30894267/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "30894267", "forPmid": "28215665", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32771-5/fulltext", "scope": "Full short official publisher correction read in Chrome. Original-article title and link matched to HERA final analysis DOI10.1016/S0140-6736(16)32616-2. Review concerns the stated correction scope; the original full article, corrected disclosures and patient-level data were not independently audited.", "summary": "The notice corrects declarations of interest for several named authors and states that the online version was updated. It does not identify changes to efficacy or safety results. The numerical DFS and OS statements in the proposed unit therefore remain supported by the saved final abstract." } }, { "type": "ErratumIn", "pmid": "28792849", "refSource": "N Engl J Med. 2017 Oct 26;377(17):1700. doi: 10.1056/NEJMx170012.", "forPmid": "28578601", "forKey": "P-OlympiAD", "title": "Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28792849/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "28792849", "forPmid": "28578601", "type": "ErratumIn", "doi": "10.1056/NEJMx170012", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx170012", "scope": "Complete official short correction read in visible browser; original title/DOI and PubMed ErratumIn/For linkage verified. Review limited to notice scope; original patient-level data and full corrected article not independently audited.", "summary": "The print edition omitted the authors’ disclosure statement. The notice supplies those conflicts of interest and says the online article is correct. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "28700263", "refSource": "N Engl J Med. 2017 Aug 17;377(7):702. doi: 10.1056/NEJMx170011.", "forPmid": "28581356", "forKey": "P-APHINITY17", "title": "Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28700263/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "28700263", "forPmid": "28581356", "type": "ErratumIn", "doi": "10.1056/NEJMx170011", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx170011", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "The authors' disclosure statement had been omitted from the print edition and was supplied. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "30338958", "refSource": "N Engl J Med. 2018 Oct 18;379(16):1585.", "forPmid": "28581356", "forKey": "P-APHINITY17", "title": "Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations; Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30338958/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "30338958", "forPmid": "28581356", "type": "ErratumIn", "doi": "10.1056/NEJMx180036", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx180036", "scope": "Complete official short correction read in a visible browser on the publisher site; the notice covers two articles and its PubMed ErratumFor linkage to this article was verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "Disclosure information for one author was inaccurate and an expanded disclosure statement was added; the editors noted that the author had failed to disclose financial associations. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "28884691", "refSource": "Lancet Oncol. 2017 Sep;18(9):510. doi: 10.1016/S1470-2045(17)30638-1.", "forPmid": "28734759", "forKey": "P-CM142mono", "title": "Correction to Lancet Oncol 2017; 18: 1182-91.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28884691/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "28884691", "forPmid": "28734759", "type": "ErratumIn", "doi": "10.1016/S1470-2045(17)30638-1", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30638-1/fulltext", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "The 86% (95% CI 62-95) figure for responses lasting 12 months was relabelled as a Kaplan-Meier 12-month estimate, and an earlier database lock date was corrected to September 2016. The numerical estimates themselves were not changed." } }, { "type": "ErratumIn", "pmid": "30507432", "refSource": "Lancet Oncol. 2018 Dec;19(12):e668. doi: 10.1016/S1470-2045(18)30843-X.", "forPmid": "30355453", "forKey": "P-TAGS", "title": "Correction to Lancet Oncol 2018; 19: 1437-48.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30507432/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "30507432", "forPmid": "30355453", "type": "ErratumIn", "refSource": "Lancet Oncol. 2018 Dec;19(12):e668. doi: 10.1016/S1470-2045(18)30843-X.", "doi": "10.1016/S1470-2045(18)30843-X", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30843-X/fulltext", "scope": "Complete official publisher correction read directly in Chrome and linked original article matched to PubMed. Assessment is limited to the proposed evidence claim and notice scope; corrected figures, tables, appendices and patient data were not independently audited. The current official publisher abstract was also read for the cited values or corrected comparator.", "summary": "Several Figure 3 points and an x-axis scale value were corrected, as was an x-axis scale value in appendix Figure 1. The notice also mentions other minor errors without itemizing them; changes were applied online on November 28, 2018. The proposed claim uses the overall-survival and adverse-event values in the saved official abstract; these were also directly checked against the current publisher abstract. No subgroup or corrected-figure estimate is used. The unspecified minor errors are not claimed to have been independently audited." } }, { "type": "ErratumIn", "pmid": "30614468", "refSource": "Lancet Oncol. 2019 Jan;20(1):e10. doi: 10.1016/S1470-2045(18)30926-4.", "forPmid": "30509771", "forKey": "P-NSABPB42", "title": "Correction to Lancet Oncol 2019; 20: 88-99.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30614468/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "30614468", "forPmid": "30509771", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30926-4/fulltext", "scope": "Full publisher correction read in the browser by root and visible notice text saved; underlying patient data were not audited.", "summary": "The notice corrects only the article title, applied online January 3, 2019; the printed version is correct. It does not amend the primary DFS estimates or significance threshold used here." } }, { "type": "ErratumIn", "pmid": "31044719", "refSource": "Lancet Oncol. 2019 May;20(5):e242. doi: 10.1016/S1470-2045(19)30244-X.", "forPmid": "30718072", "forKey": "P-RAINFALL", "title": "Correction to Lancet Oncol 2019; 20: 420-35.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31044719/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "31044719", "forPmid": "30718072", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30244-X/fulltext", "scope": "Full official publisher correction read in Chrome and original-article link matched. Review is limited to the existing evidence-unit claim; for SPOTLIGHT the current publisher abstract was also checked. The original full article, corrected appendix and patient-level data were not independently audited.", "summary": "Table 3 should give the ramucirumab plus chemotherapy group grade 4 gastrointestinal-haemorrhage event percentage as 1%; the correction was applied April 30, 2019. The existing unit cites PFS and OS only. The corrected adverse-event percentage is not added to its abstract-only numeric claim. A separate saved-abstract context issue is recorded below." } }, { "type": "ErratumIn", "pmid": "31209337", "refSource": "Nat Med. 2019 Jul;25(7):1175. doi: 10.1038/s41591-019-0520-5.", "forPmid": "31086347", "forKey": "P-PM31086347", "title": "Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.", "text": "In the version of this article originally published, there was an error in Fig. 3j. A label on the heatmap read \"TGF-α signaling via NF-κB\". It should have read \"TNF-α signaling via NF-κB\". The error has been corrected in the HTML and PDF versions of this article.", "url": "https://pubmed.ncbi.nlm.nih.gov/31209337/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "35595658", "refSource": "Ann Oncol. 2022 Jul;33(7):743-744. doi: 10.1016/j.annonc.2022.04.003.", "forPmid": "31095287", "forKey": "P-PM31095287", "title": "Corrigendum to \"A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study\": [Annals of Oncology (2019), volume 30:1279-1288].", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35595658/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "31917389", "refSource": "JAMA Oncol. 2020 Jan 1;6(1):162. doi: 10.1001/jamaoncol.2019.6325.", "forPmid": "31369045", "forKey": "P-ctDNAGarcia19", "title": "Errors in Results.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31917389/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "31917389", "forPmid": "31369045", "type": "ErratumIn", "doi": "10.1001/jamaoncol.2019.6325", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11845095/", "scope": "Complete official short correction read in a visible browser on PubMed Central (the publisher page showed an automated security check and was not used); original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "Three figures in the Results were corrected: validated assays were developed for 90.9% of mutations rather than 91.5%; of 29 patients who relapsed, 23 (79.3%, not 88.4%) had prior ctDNA detection and 6 (20.7%, not 21.6%) relapsed without it. The hazard ratios, lead time and site-specific detection counts in the abstract were not changed." } }, { "type": "ErratumIn", "pmid": "31950142", "refSource": "Jpn J Clin Oncol. 2020 Feb 17;50(2):223. doi: 10.1093/jjco/hyz208.", "forPmid": "31612909", "forKey": "P-PM31612909", "title": "Corrigendum to: Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130).", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31950142/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "39914428", "refSource": "Lancet Oncol. 2025 Feb;26(2):e77. doi: 10.1016/S1470-2045(25)00014-2.", "forPmid": "31668850", "forKey": "P-PM31668850", "title": "Correction to Lancet Oncol 2019; 20: 1750-59.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39914428/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "32135071", "refSource": "J Clin Oncol. 2020 Mar 10;38(8):847. doi: 10.1200/JCO.20.00164.", "forPmid": "31804894", "forKey": "P-PM31804894", "title": "Errata.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32135071/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "31881136", "refSource": "N Engl J Med. 2020 Feb 6;382(6):586. doi: 10.1056/NEJMx190039.", "forPmid": "31825569", "forKey": "P-HER2CLIMB", "title": "Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31881136/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "31881136", "forPmid": "31825569", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx190039", "scope": "Complete public publisher correction read in the Chrome browser and the original-article DOI link matched. Review is limited to the existing evidence-unit claim and saved official PubMed abstract; the full original article and patient-level data were not independently audited.", "summary": "The Safety subsection is replaced with a more specific account of one patient who met laboratory Hy’s-law criteria, recovered after dose modification, continued treatment, and was subsequently judged by an independent hepatology review not to be a true Hy’s-law case. The notice concerns characterization of a liver-safety event, not the efficacy endpoint. The current unit uses PFS estimates only and omits the affected individual liver-event classification." } }, { "type": "ErratumIn", "pmid": "33688930", "refSource": "JAMA Surg. 2021 May 1;156(5):503. doi: 10.1001/jamasurg.2021.0396.", "forPmid": "31913413", "forKey": "P-PM31913413", "title": "Error in Author's Name.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33688930/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33662298", "refSource": "Lancet Oncol. 2021 Mar;22(3):e92. doi: 10.1016/S1470-2045(21)00032-2.", "forPmid": "32353342", "forKey": "P-PM32353342", "title": "Correction to Lancet Oncol 2020; 21: 763-75.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33662298/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34735814", "refSource": "Lancet Oncol. 2021 Nov;22(11):e472. doi: 10.1016/S1470-2045(21)00587-8.", "forPmid": "32353342", "forKey": "P-PM32353342", "title": "Correction to Lancet Oncol 2020; 21: 763-75.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34735814/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "35226359", "refSource": "Int J Cancer. 2022 Jun 1;150(11):E9. doi: 10.1002/ijc.33979.", "forPmid": "32488909", "forKey": "P-PM32488909", "title": "Erratum.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35226359/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33331846", "refSource": "JAMA Oncol. 2021 Jan 1;7(1):140. doi: 10.1001/jamaoncol.2020.7303.", "forPmid": "33151286", "forKey": "P-PM33151286", "title": "Error in Author Name.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33331846/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33387508", "refSource": "Lancet Oncol. 2021 Jan;22(1):e5. doi: 10.1016/S1470-2045(20)30733-6.", "forPmid": "33152277", "forKey": "P-PM33152277", "title": "Correction to Lancet Oncol 2020; 21: 1602-10.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33387508/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33271112", "refSource": "Lancet Oncol. 2020 Dec;21(12):e553. doi: 10.1016/S1470-2045(20)30677-X.", "forPmid": "33152284", "forKey": "P-PM33152284", "title": "Correction to Lancet Oncol 2020; 21: 1443-54.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33271112/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33539749", "refSource": "Lancet Oncol. 2021 Feb;22(2):e42. doi: 10.1016/S1470-2045(20)30781-6.", "forPmid": "33301740", "forKey": "P-RAPIDO", "title": "Correction to Lancet Oncol 2021; 22: 29-42.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33539749/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "33539749", "forPmid": "33301740", "type": "ErratumIn", "refSource": "Lancet Oncol. 2021 Feb;22(2):e42. doi: 10.1016/S1470-2045(20)30781-6.", "doi": "10.1016/S1470-2045(20)30781-6", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30781-6/fulltext", "scope": "Complete official publisher correction read directly in Chrome and linked original article matched to PubMed. Assessment is limited to the proposed evidence claim and notice scope; corrected figures, tables, appendices and patient data were not independently audited.", "summary": "Figure 1 must identify 185 of the 187 standard-care patients receiving adjuvant chemotherapy as receiving it according to hospital policy. The correction was applied online on February 1, 2021. This flow-diagram classification correction is not used to alter the primary disease-related treatment-failure estimates or the separate later locoregional-failure report. Optional adjuvant therapy remains a feature of the standard-care strategy; the unit does not infer a randomized effect of receiving adjuvant chemotherapy." } }, { "type": "ErratumIn", "pmid": "33539750", "refSource": "Lancet Oncol. 2021 Feb;22(2):e42. doi: 10.1016/S1470-2045(21)00010-3.", "forPmid": "33357420", "forKey": "P-PM33357420", "title": "Correction to Lancet Oncol 2021; 22: 85-97.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33539750/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36174627", "refSource": "Lancet Oncol. 2022 Oct;23(10):e446. doi: 10.1016/S1470-2045(22)00572-1.", "forPmid": "33387497", "forKey": "P-PM33387497", "title": "Correction to Lancet Oncol 2021; 22: 74-84.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36174627/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36990612", "refSource": "Lancet Oncol. 2023 Apr;24(4):e146. doi: 10.1016/S1470-2045(23)00116-X.", "forPmid": "33387497", "forKey": "P-PM33387497", "title": "Correction to Lancet Oncol 2021; 22: 74-84.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36990612/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "33750608", "refSource": "Eur J Cancer. 2021 May;148:451-452. doi: 10.1016/j.ejca.2021.02.004.", "forPmid": "33388491", "forKey": "P-PM33388491", "title": "Corrigendum to \"Leuprorelin combined with letrozole with/without everolimus in ovarian-suppressed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer: The LEO studyˮ [Eur J Canc 144 (2021) 341-350].", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33750608/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34706213", "refSource": "J Clin Oncol. 2021 Nov 1;39(31):3525. doi: 10.1200/JCO.21.02277.", "forPmid": "33769862", "forKey": "P-PM33769862", "title": "Erratum.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34706213/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36827621", "refSource": "J Clin Oncol. 2023 Apr 20;41(12):2299-2301. doi: 10.1200/JCO.23.00175.", "forPmid": "33769862", "forKey": "P-PM33769862", "title": "Erratum: Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36827621/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36791183", "refSource": "N Engl J Med. 2023 Feb 16;388(7):672. doi: 10.1056/NEJMx220014.", "forPmid": "33789008", "forKey": "P-CM577", "title": "Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36791183/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "36791183", "forPmid": "33789008", "type": "ErratumIn", "doi": "10.1056/NEJMx220014", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx220014", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "A baseline table row was relabelled from tumour location at initial diagnosis to tumour location at trial entry, and its patient counts by location were corrected in both groups; a figure label was corrected likewise. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "33910604", "refSource": "Breast Cancer Res. 2021 Apr 28;23(1):50. doi: 10.1186/s13058-021-01432-9.", "forPmid": "33849606", "forKey": "P-PM33849606", "title": "Correction to: IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33910604/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34043103", "refSource": "Int J Clin Oncol. 2021 Jul;26(7):1237. doi: 10.1007/s10147-021-01940-w.", "forPmid": "33891194", "forKey": "P-PM33891194", "title": "Correction to: Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19).", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34043103/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36166110", "refSource": "Int J Clin Oncol. 2022 Nov;27(11):1793. doi: 10.1007/s10147-022-02237-2.", "forPmid": "33891194", "forKey": "P-PM33891194", "title": "Correction to: Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19).", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36166110/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34412950", "refSource": "Ann Oncol. 2021 Oct;32(10):1307. doi: 10.1016/j.annonc.2021.07.011.", "forPmid": "34102253", "forKey": "P-PM34102253", "title": "Corrigendum to 'Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival': [Annals of Oncology Volume 32, Issue 8, August 2021, Pages 1015-1024].", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34412950/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34534460", "refSource": "Lancet Diabetes Endocrinol. 2021 Oct;9(10):e4. doi: 10.1016/S2213-8587(21)00247-3.", "forPmid": "34118198", "forKey": "P-T-ARROW21", "title": "Correction to Lancet Diabetes Endocrinol 2021; 9: 491-501.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34534460/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "34534460", "forPmid": "34118198", "type": "ErratumIn", "doi": "10.1016/S2213-8587(21)00247-3", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00247-3/fulltext", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the corrected article was not independently audited.", "summary": "The first sentence of the Introduction (share of medullary cancer among thyroid cancers) was reworded. No result used in the library unit was changed." } }, { "type": "ErratumIn", "pmid": "34383001", "refSource": "JAMA Oncol. 2021 Sep 1;7(9):1405-1406. doi: 10.1001/jamaoncol.2021.4021.", "forPmid": "34165503", "forKey": "P-PM34165503", "title": "Errors in Abstract and Results.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34383001/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34339653", "refSource": "Lancet Oncol. 2021 Aug;22(8):e347. doi: 10.1016/S1470-2045(21)00417-4.", "forPmid": "34252374", "forKey": "P-RESOLVE", "title": "Correction to Lancet Oncol 2021; 22: 1081-92.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34339653/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "34339653", "forPmid": "34252374", "type": "ErratumIn", "refSource": "Lancet Oncol. 2021 Aug;22(8):e347. doi: 10.1016/S1470-2045(21)00417-4.", "doi": "10.1016/S1470-2045(21)00417-4", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00417-4/fulltext", "scope": "Complete official publisher correction read directly in Chrome and linked original article matched to PubMed. Assessment is limited to the proposed evidence claim and notice scope; corrected figures, tables, appendices and patient data were not independently audited.", "summary": "A Results appendix page reference was changed. Two erroneous group labels in the Table 2 legend were replaced by adjuvant-SOX, and Appendix 2 was updated. Changes were applied online on July 30, 2021; the notice states the printed version was correct. The proposed unit uses the reported modified intention-to-treat disease-free-survival comparisons and the subsequent final overall-survival report. No estimate is extracted from the corrected table legend or appendix; those underlying artifacts were not independently audited." } }, { "type": "ErratumIn", "pmid": "39914427", "refSource": "Lancet Oncol. 2025 Feb;26(2):e77. doi: 10.1016/S1470-2045(25)00015-4.", "forPmid": "34252374", "forKey": "P-RESOLVE", "title": "Correction to Lancet Oncol 2021; 22: 1081-92.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39914427/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "39914427", "forPmid": "34252374", "type": "ErratumIn", "refSource": "Lancet Oncol. 2025 Feb;26(2):e77. doi: 10.1016/S1470-2045(25)00015-4.", "doi": "10.1016/S1470-2045(25)00015-4", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00015-4/fulltext", "scope": "Complete official publisher correction read directly in Chrome and linked original article matched to PubMed. Assessment is limited to the proposed evidence claim and notice scope; corrected figures, tables, appendices and patient data were not independently audited. The current official publisher abstract was also read for the cited values or corrected comparator.", "summary": "The primary-endpoint sentence in Summary Methods was corrected: the superiority comparison is perioperative-SOX versus adjuvant-CapOx, while the non-inferiority comparison is adjuvant-SOX versus adjuvant-CapOx with an HR margin of 1.33. The change was applied online on February 3, 2025. The saved primary PubMed abstract still names adjuvant-SOX as the superiority comparator. The current publisher abstract and final report instead agree with the correction. The raw PubMed record is preserved; the proposed claim uses the corrected adjuvant-CapOx comparison and does not infer superiority between the two SOX strategies." } }, { "type": "ErratumIn", "pmid": "36996379", "refSource": "JCO Precis Oncol. 2023 Mar;7:e2300102. doi: 10.1200/PO.23.00102.", "forPmid": "34504990", "forKey": "P-PM34504990", "title": "Erratum.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36996379/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "34792545", "refSource": "JAMA Oncol. 2021 Nov 1;7(11):1729. doi: 10.1001/jamaoncol.2021.6304.", "forPmid": "34617955", "forKey": "P-PM34617955", "title": "Error in Author Affiliations and Supplement.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34792545/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36239018", "refSource": "Clin Cancer Res. 2022 Oct 14;28(20):4587. doi: 10.1158/1078-0432.CCR-22-2874.", "forPmid": "35121623", "forKey": "P-PM35121623", "title": "Correction: Clinical Significance of PIK3CA and ESR1 Mutations in Circulating Tumor DNA: Analysis from the MONARCH 2 Study of Abemaciclib plus Fulvestrant.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36239018/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "35389424", "refSource": "JAMA Oncol. 2022 May 01;8(5):784. doi: 10.1001/jamaoncol.2022.0909.", "forPmid": "35238873", "forKey": "P-PM35238873", "title": "Error in Author Surname.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/35389424/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36170752", "refSource": "J Clin Oncol. 2022 Oct 1;40(28):3352. doi: 10.1200/JCO.22.01890.", "forPmid": "35442755", "forKey": "P-PM35442755", "title": "Erratum.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36170752/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "37364222", "refSource": "J Clin Oncol. 2023 Aug 10;41(23):3962. doi: 10.1200/JCO.23.01239.", "forPmid": "35584336", "forKey": "P-EMERALD", "title": "Erratum: Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37364222/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "37364222", "forPmid": "35584336", "type": "ErratumIn", "refSource": "J Clin Oncol. 2023 Aug 10;41(23):3962. doi: 10.1200/JCO.23.01239.", "doi": "10.1200/JCO.23.01239", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://ascopubs.org/doi/10.1200/JCO.23.01239", "scope": "Full official publisher correction read in Chrome and its linked original-article DOI matched to the saved PubMed record. Assessment is limited to the existing evidence-unit claim and the correction scope. Corrected figures, tables, appendices and patient-level data were not independently audited.", "summary": "The fulvestrant-only Kaplan-Meier curves in Figure 1 panels C and D were replaced after incorrectly duplicating panels A and B. Supplementary Figure S5 panel B changes a six-month overall-survival confidence interval to 88.7-97.8, and supplementary Table S3 changes the all-patient hazard-ratio confidence interval to 0.63-0.95. The correction was applied June 26, 2023. The existing claim uses the primary PFS hazard ratios for all patients and the ESR1-mutant population, both supported by the saved abstract. It does not cite the fulvestrant-only curves, six-month OS interval or supplementary hazard ratio. This notice does not amend the two cited primary PFS hazard ratios. Do not transfer the primary all-patient comparison to a fulvestrant-only comparison, or imply that the corrected curves and supplementary estimates were independently reproduced." } }, { "type": "ErratumIn", "pmid": "36550442", "refSource": "BMC Cancer. 2022 Dec 22;22(1):1348. doi: 10.1186/s12885-022-10455-0.", "forPmid": "36071409", "forKey": "P-PM36071409", "title": "Correction: Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36550442/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "36803433", "refSource": "Lancet. 2023 Feb 18;401(10376):556. doi: 10.1016/S0140-6736(22)00045-9.", "forPmid": "36495879", "forKey": "P-PM36495879", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36803433/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "37171785", "refSource": "Breast Cancer. 2023 Jul;30(4):606. doi: 10.1007/s12282-023-01468-z.", "forPmid": "37005966", "forKey": "P-PM37005966", "title": "Correction: Adjuvant olaparib in the subset of patients from Japan with BRCA1- or BRCA2-mutated high-risk early breast cancer from the phase 3 OlympiA trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37171785/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "37815173", "refSource": "Oncologist. 2024 Apr 4;29(4):e579. doi: 10.1093/oncolo/oyad287.", "forPmid": "37036671", "forKey": "P-PM37036671", "title": "Correction to: AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37815173/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "37481269", "refSource": "Lancet. 2023 Jul 22;402(10398):290. doi: 10.1016/S0140-6736(23)01481-2.", "forPmid": "37068504", "forKey": "P-SPOTLIGHT", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37481269/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "37481269", "forPmid": "37068504", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01481-2/fulltext", "scope": "Full official publisher correction read in Chrome and original-article link matched. Review is limited to the existing evidence-unit claim; for SPOTLIGHT the current publisher abstract was also checked. The original full article, corrected appendix and patient-level data were not independently audited.", "summary": "The statistical-analysis and eligibility sections are directed to corrected appendix page ranges, and the appendix itself was corrected as of July 20, 2023. This review does not certify the corrected appendix or its statistical-analysis plan. Existing efficacy figures were checked against the current public publisher abstract." } }, { "type": "ErratumIn", "pmid": "38101428", "refSource": "Lancet. 2024 Jan 6;403(10421):30. doi: 10.1016/S0140-6736(23)02762-9.", "forPmid": "37068504", "forKey": "P-SPOTLIGHT", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38101428/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "38101428", "forPmid": "37068504", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02762-9/fulltext", "scope": "Full official publisher correction read in Chrome and original-article link matched. Review is limited to the existing evidence-unit claim; for SPOTLIGHT the current publisher abstract was also checked. The original full article, corrected appendix and patient-level data were not independently audited.", "summary": "The notice replaces grade-specific descriptions of the most common nausea, vomiting and decreased appetite with all-grade wording, explains more nausea/vomiting-related discontinuation with zolbetuximab, and states that small gastro-oesophageal-junction subgroups do not support PFS or OS conclusions. It also corrects appendix references, a White-race placebo event count in a forest plot, adds a dyspnoea row, revises Discussion wording and amends the appendix. Corrections were applied December 12, 2023. The stored PubMed abstract still uses the superseded grade-specific wording. The current publisher abstract uses all-grade. Keep the original source bytes and explicitly identify this discrepancy; do not infer a GEJ-specific efficacy benefit from the overall trial. No appendix-derived claim is included." } }, { "type": "ErratumIn", "pmid": "37367990", "refSource": "JAMA. 2023 Jun 27;329(24):2196. doi: 10.1001/jama.2023.10533.", "forPmid": "37071094", "forKey": "P-PARADIGM", "title": "Error in Text Wording and Incorrect Reference.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37367990/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "37367990", "forPmid": "37071094", "type": "ErratumIn", "doi": "10.1001/jama.2023.10533", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10300671/", "scope": "Complete official short correction read in a visible browser on PubMed Central; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the corrected article and supplement were not independently audited.", "summary": "A Discussion sentence about second-line treatment duration in another trial (FIRE-3) was reworded from longer to shorter, one reference was replaced and Supplement 3 was changed. No abstract value used in the library unit was changed." } }, { "type": "ErratumIn", "pmid": "37364217", "refSource": "J Clin Oncol. 2023 Aug 10;41(23):3962. doi: 10.1200/JCO.23.01230.", "forPmid": "37079878", "forKey": "P-PM37079878", "title": "Erratum: Postoperative Adjuvant Anastrozole for 10 or 5 Years in Patients With Hormone Receptor-Positive Breast Cancer: AERAS, a Randomized Multicenter Open-Label Phase III Trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37364217/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38070948", "refSource": "Lancet. 2023 Dec 9;402(10418):2196. doi: 10.1016/S0140-6736(23)02709-5.", "forPmid": "37086745", "forKey": "P-DB02", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38070948/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "38070948", "forPmid": "37086745", "type": "ErratumIn", "doi": "10.1016/S0140-6736(23)02709-5", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02709-5/fulltext", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "Subheadings under Visceral disease in figure 2 (subgroup display) were corrected online. The notice does not change the overall progression-free survival, safety or interstitial lung disease figures used in this record; subgroup values are not adopted here." } }, { "type": "ErratumIn", "pmid": "38460989", "refSource": "Lancet. 2024 Mar 9;403(10430):912. doi: 10.1016/S0140-6736(24)00420-3.", "forPmid": "37086745", "forKey": "P-DB02", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38460989/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "38460989", "forPmid": "37086745", "type": "ErratumIn", "doi": "10.1016/S0140-6736(24)00420-3", "reviewedAt": "2026-10-06", "by": "Claude", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00420-3/fulltext", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "One author's affiliation and the formatting of another author's name were corrected online. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "37766422", "refSource": "J Natl Cancer Inst. 2023 Nov 8;115(11):1437. doi: 10.1093/jnci/djad197.", "forPmid": "37184928", "forKey": "P-NSABPB42-10y", "title": "Correction to: Ten-year update: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial: extended letrozole therapy in early-stage breast cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37766422/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "37766422", "forPmid": "37184928", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://academic.oup.com/jnci/article/115/11/1437/7284424", "scope": "Full official correction notice content retrieved through web search; the original full article and underlying patient data were not independently audited.", "summary": "The notice corrects a Discussion citation about estrogen levels and bone mineral density, adds the correct study and an endocrine-therapy toxicity systematic review to the bibliography, and renumbers subsequent citations. It does not amend the efficacy or safety estimates in the abstract used for U-NSABPB42." } }, { "type": "ErratumIn", "pmid": "37516694", "refSource": "Surg Endosc. 2023 Sep;37(9):7393-7394. doi: 10.1007/s00464-023-10336-y.", "forPmid": "37468751", "forKey": "P-PM37468751", "title": "Correction: Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37516694/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38867085", "refSource": "Gastric Cancer. 2024 Sep;27(5):1157. doi: 10.1007/s10120-024-01519-0.", "forPmid": "37548812", "forKey": "P-JACCROGC07", "title": "Correction: Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38867085/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "38867085", "forPmid": "37548812", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://link.springer.com/article/10.1007/s10120-024-01519-0", "scope": "Full publisher correction read via web and saved HTML; original article abstract and corrected Results context checked. Underlying patient data were not audited.", "summary": "The Results paragraph had mislabeled 190 and 236 as patients with recurrence and separately cited deaths. The notice replaces this with 426 observed events during five years: 190 with S-1 plus docetaxel and 236 with S-1 alone. The article was corrected as of May 22, 2024. The curated unit avoids the erroneous recurrence counts; the notice does not amend its abstract survival estimates." } }, { "type": "ErratumIn", "pmid": "37922932", "refSource": "Lancet Oncol. 2023 Nov;24(11):e425. doi: 10.1016/S1470-2045(23)00482-5.", "forPmid": "37657462", "forKey": "P-PM37657462", "title": "Correction to Lancet Oncology 2023; 24: 1029-41.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37922932/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "39938112", "refSource": "N Engl J Med. 2025 Feb 13;392(7):728. doi: 10.1056/NEJMx240006.", "forPmid": "37870968", "forKey": "P-CodeBreaK300", "title": "Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39938112/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "39938112", "forPmid": "37870968", "type": "ErratumIn", "doi": "10.1056/NEJMx240006", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx240006", "scope": "Complete official correction notice read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the corrected full article was not independently audited.", "summary": "A reanalysis with a later data snapshot and the same data cutoff changed abstract values: median progression-free survival 3.9 months (95% CI 3.6 to 5.7) for the 240-mg group and 2.0 months for standard care, hazard ratios 0.48 (95% CI 0.30 to 0.78; P=0.005) for 960 mg and 0.59 (95% CI 0.37 to 0.95; P=0.036) for 240 mg, and the conclusion now attributes significantly longer progression-free survival to the 960-mg dose only. The library unit uses the corrected values and links the notice." } }, { "type": "ErratumIn", "pmid": "39637898", "refSource": "Lancet Oncol. 2024 Dec;25(12):e626. doi: 10.1016/S1470-2045(24)00650-8.", "forPmid": "37875143", "forKey": "P-KN859", "title": "Correction to Lancet Oncol 2023; 24: 1181-95.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39637898/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "39637898", "forPmid": "37875143", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00650-8/fulltext", "scope": "Complete public publisher correction read in the Chrome browser and the original-article DOI link matched. Review is limited to the existing evidence-unit claim and saved official PubMed abstract; the full original article and patient-level data were not independently audited.", "summary": "The correction restores an omitted hazard-ratio data point for the no-liver-metastases subgroup in Figure 2D. It was applied online on December 2, 2024. The current unit uses ITT overall survival and omits the affected subgroup figure." } }, { "type": "ErratumIn", "pmid": "37973164", "refSource": "BMJ. 2023 Nov 16;383:p2665. doi: 10.1136/bmj.p2665.", "forPmid": "37907210", "forKey": "P-PHILA", "title": "Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37973164/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "37973164", "forPmid": "37907210", "type": "ErratumIn", "doi": "10.1136/bmj.p2665", "reviewedAt": "2026-10-11", "by": "Claude", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10652813/", "scope": "Complete official short correction read in a visible browser on PubMed Central; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "One author's affiliation was corrected. It does not report an efficacy or safety estimate correction." } }, { "type": "ErratumIn", "pmid": "38086864", "refSource": "Nat Commun. 2023 Dec 12;14(1):8223. doi: 10.1038/s41467-023-44071-8.", "forPmid": "37919269", "forKey": "P-PM37919269", "title": "Author Correction: Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38086864/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38191616", "refSource": "Nat Med. 2024 Feb;30(2):605. doi: 10.1038/s41591-024-02800-6.", "forPmid": "38167937", "forKey": "P-PM38167937", "title": "Author Correction: Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38191616/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38448792", "refSource": "Nat Med. 2024 May;30(5):1499. doi: 10.1038/s41591-024-02898-8.", "forPmid": "38191613", "forKey": "P-PM38191613", "title": "Author Correction: Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38448792/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38547897", "refSource": "Lancet Oncol. 2024 Apr;25(4):e137. doi: 10.1016/S1470-2045(24)00144-X.", "forPmid": "38342115", "forKey": "P-PM38342115", "title": "Correction to Lancet Oncol 2024; 25: 317-25.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38547897/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38936385", "refSource": "Lancet Oncol. 2024 Jul;25(7):e284. doi: 10.1016/S1470-2045(24)00289-4.", "forPmid": "38342115", "forKey": "P-PM38342115", "title": "Correction to Lancet Oncol 2024; 25: 317-25.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38936385/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38730268", "refSource": "Nat Commun. 2024 May 10;15(1):3957. doi: 10.1038/s41467-024-48359-1.", "forPmid": "38538574", "forKey": "P-PM38538574", "title": "Author Correction: Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38730268/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "41093689", "refSource": "Ann Oncol. 2025 Dec;36(12):1556. doi: 10.1016/j.annonc.2025.07.002.", "forPmid": "38729566", "forKey": "P-PM38729566", "title": "Corrigendum to \"Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3\": [Ann Oncol 2024; 35: 718-727].", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41093689/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "38985490", "refSource": "JAMA Surg. 2024 Aug 1;159(8):960. doi: 10.1001/jamasurg.2024.2710.", "forPmid": "38809537", "forKey": "P-PM38809537", "title": "Error in Author Affiliation.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38985490/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "40088908", "refSource": "Lancet Gastroenterol Hepatol. 2025 Apr;10(4):e7. doi: 10.1016/S2468-1253(25)00047-0.", "forPmid": "38906161", "forKey": "P-ATT5", "title": "Correction to Lancet Gastroenterol Hepatol 2024; 9: 705-17.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40088908/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "40088908", "forPmid": "38906161", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/langas/article/PIIS2468-1253(25)00047-0/fulltext", "scope": "Full correction notice and current publisher abstract read in browser; original full article and underlying patient data not independently audited.", "summary": "Treatment-discontinuation wording was corrected to treatment-related adverse events. Other corrections concern treatment completion, rounding, a figure confidence-level label, diarrhoea and deaths. The current abstract retains the cited primary relapse-free-survival estimate and adjusted interval. U-ATT5 now uses the corrected safety wording." } }, { "type": "ErratumIn", "pmid": "40049203", "refSource": "Lancet Oncol. 2025 Mar;26(3):e127. doi: 10.1016/S1470-2045(25)00036-1.", "forPmid": "39481395", "forKey": "P-PM39481395", "title": "Correction to Lancet Oncol 2024; 25: 1424-39.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40049203/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "40696185", "refSource": "Nature. 2025 Aug;644(8076):E32. doi: 10.1038/s41586-025-09406-z.", "forPmid": "39604725", "forKey": "P-PM39604725", "title": "Author Correction: Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40696185/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "39939996", "refSource": "BMC Med. 2025 Feb 12;23(1):83. doi: 10.1186/s12916-025-03938-x.", "forPmid": "39696266", "forKey": "P-PM39696266", "title": "Correction: Efficacy, safety, and biomarker analysis of first-line immune checkpoint inhibitors with chemotherapy versus chemotherapy for advanced gastric cancer: a multicenter, retrospective cohort study.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39939996/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "39919260", "refSource": "J Clin Oncol. 2025 Mar 10;43(8):1045. doi: 10.1200/JCO-25-00116.", "forPmid": "39772884", "forKey": "P-PM39772884", "title": "Erratum: Fulvestrant Versus Anastrozole in Endocrine Therapy-Naïve Women With Hormone Receptor-Positive Advanced Breast Cancer: Final Overall Survival in the Phase III FALCON Trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39919260/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "40140623", "refSource": "Nat Med. 2025 Apr;31(4):1368. doi: 10.1038/s41591-025-03666-y.", "forPmid": "39843940", "forKey": "P-COMPASSION15", "title": "Author Correction: First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40140623/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "40140623", "forPmid": "39843940", "type": "ErratumIn", "doi": "10.1038/s41591-025-03666-y", "reviewedAt": "2026-10-07", "by": "Claude", "url": "https://www.nature.com/articles/s41591-025-03666-y", "scope": "Complete official short correction read in a visible browser on the publisher site; original title and PubMed ErratumIn linkage verified. Review limited to the notice; the full corrected article was not independently audited.", "summary": "Missing subgroup labels were added to one figure, the y-axis labels of the progression-free survival figure were corrected from overall survival, and the hazard ratio shown in that figure was corrected to 0.53, which is the value in the abstract." } }, { "type": "ErratumIn", "pmid": "40215433", "refSource": "J Clin Oncol. 2025 May 10;43(14):1749. doi: 10.1200/JCO-25-00722.", "forPmid": "39854662", "forKey": "P-PM39854662", "title": "Erratum: Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40215433/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "40023649", "refSource": "Lancet. 2025 Mar 1;405(10480):700. doi: 10.1016/S0140-6736(25)00352-6.", "forPmid": "39874977", "forKey": "P-CM8HWNIVO", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40023649/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "40023649", "forPmid": "39874977", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00352-6/fulltext", "scope": "Full publisher correction read in the browser and its original-article link matched; the current publisher abstract was read and compared with the saved PubMed abstract. The corrected appendix, full original article and underlying patient data were not independently audited.", "summary": "The notice states that the appendix was corrected as of February 27, 2025, without specifying individual changes. The proposed unit makes no appendix-derived claims. Its central-confirmation denominators, PFS estimate and safety figures match the current publisher abstract and saved PubMed abstract. Review is limited to these abstract-supported claims and does not certify the appendix." } }, { "type": "ErratumIn", "pmid": "40179913", "refSource": "Lancet Oncol. 2025 Apr;26(4):e186. doi: 10.1016/S1470-2045(25)00144-5.", "forPmid": "40049198", "forKey": "P-PM40049198", "title": "Correction to Lancet Oncol 2025; 26: 367-77.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40179913/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "40542173", "refSource": "Br J Cancer. 2025 Aug;133(2):274. doi: 10.1038/s41416-025-03092-4.", "forPmid": "40399487", "forKey": "P-PM40399487", "title": "Correction: Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/40542173/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "41219392", "refSource": "Br J Cancer. 2025 Dec;133(12):1928. doi: 10.1038/s41416-025-03267-z.", "forPmid": "40399487", "forKey": "P-PM40399487", "title": "Correction: Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41219392/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42933445", "refSource": "Lancet Oncol. 2026 Nov;27(11):e537. doi: 10.1016/S1470-2045(26)00543-7.", "forPmid": "40516558", "forKey": "P-PM40516558", "title": "Correction to Lancet Oncol 2025; 26: 898-910.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42933445/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42845262", "refSource": "J Gastric Cancer. 2026 Oct;26(4):634-636. doi: 10.5230/jgc.2026.26.e41.", "forPmid": "40631473", "forKey": "P-PM40631473", "title": "Erratum: Safety and Efficacy of Reduced-Port Versus Conventional Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Multicenter, Randomized, Non-inferiority Trial (KLASS-12).", "text": "This corrects the article on p. 437 in vol. 25, PMID: 40631473.", "url": "https://pubmed.ncbi.nlm.nih.gov/42845262/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "41651836", "refSource": "Nat Commun. 2026 Feb 6;17(1):1437. doi: 10.1038/s41467-026-69394-0.", "forPmid": "40640119", "forKey": "P-PM40640119", "title": "Author Correction: DKN-01 and tislelizumab as second-line therapy in DKK1-high gastroesophageal adenocarcinoma: DisTinGuish trial part B.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41651836/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "41931063", "refSource": "N Engl J Med. 2026 Apr 2;394(13):1352. doi: 10.1056/NEJMx260006.", "forPmid": "41370739", "forKey": "P-DB05", "title": "Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41931063/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "41931063", "forPmid": "41370739", "type": "ErratumIn", "reviewedAt": "2026-09-30", "by": "Codex (GPT-6)", "url": "https://www.nejm.org/doi/full/10.1056/NEJMx260006", "scope": "Complete public publisher correction read in the Chrome browser and the original-article DOI link matched. Review is limited to the existing evidence-unit claim and saved official PubMed abstract; the full original article and patient-level data were not independently audited.", "summary": "The notice restores a corrupted Discussion passage about activity in tumors with lower IHC scores plus ISH amplification and the predominance of distant invasive recurrences. It specifies distant-event counts for the two arms. It does not amend the abstract IDFS or ILD estimates used in the current unit. The stale full-notice-unreviewed wording in the unit limits should be updated when this review is integrated." } }, { "type": "ErratumIn", "pmid": "41526043", "refSource": "BMJ. 2026 Jan 12;392:s43. doi: 10.1136/bmj.s43.", "forPmid": "41436191", "forKey": "P-PM41436191", "title": "Effect of adjuvant carboplatin intensified chemotherapy versus standard chemotherapy on survival in women with high risk, early stage, triple negative breast cancer (CITRINE): randomised, open label phase 3 trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41526043/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42817702", "refSource": "Clin Cancer Res. 2026 Oct 1;32(19):4504. doi: 10.1158/1078-0432.CCR-26-2886.", "forPmid": "41661218", "forKey": "P-INTEGRAL26", "title": "Correction: A Phase II Study of Docetaxel and Pembrolizumab plus Interleukin 12 Gene Therapy in Nonmetastatic, Anthracycline-Refractory Triple-Negative Breast Cancer (INTEGRAL).", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42817702/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "42817702", "forPmid": "41661218", "type": "ErratumIn", "doi": "10.1158/1078-0432.CCR-26-2886", "reviewedAt": "2026-10-24", "by": "Codex (GPT-6)", "url": "https://aacrjournals.org/clincancerres/article/32/19/4504/788418/Correction-A-Phase-II-Study-of-Docetaxel-and", "scope": "The complete short official publisher notice paragraph and linked parent reference were returned in web search this run. Direct DOI HTML returned403; no alternate publisher URL, cache or PDF was requested. Review limited to that notice, not certification of all corrected article data or the numerical inconsistency in the parent PMC body.", "summary": "The notice adds the omitted author Ann C. Anselme and updates author contributions/disclosures. It does not amend the abstract efficacy or safety figures used here. The separate parent-body response percentage and registry response-definition discrepancy remain explicitly unresolved." } }, { "type": "ErratumIn", "pmid": "41997916", "refSource": "Nat Commun. 2026 Apr 17;17(1):3583. doi: 10.1038/s41467-026-72255-5.", "forPmid": "41760643", "forKey": "P-PM41760643", "title": "Author Correction: First-line modified FOLFOX plus/minus nivolumab and Ipilimumab or FLOT plus nivolumab in advanced gastroesophageal adenocarcinoma: a phase II multi-cohort IKF-AIO-MOONLIGHT trial.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41997916/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42241670", "refSource": "J Clin Oncol. 2026 Jul;44(19):1852. doi: 10.1200/JCO-26-01302.", "forPmid": "41802242", "forKey": "P-PM41802242", "title": "Erratum: VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42241670/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42001850", "refSource": "Cancer Cell. 2026 May 11;44(5):1097. doi: 10.1016/j.ccell.2026.04.006.", "forPmid": "41895280", "forKey": "P-MSK50K26", "title": "Cancer type-specific variation in patterns of driver alterations across 50,000 tumors.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42001850/", "unresolvedIdentifier": false, "reviewed": true, "review": { "pmid": "42001850", "forPmid": "41895280", "type": "ErratumIn", "doi": "10.1016/j.ccell.2026.04.006", "reviewedAt": "2026-10-21", "by": "Claude", "url": "https://www.cell.com/cancer-cell/fulltext/S1535-6108(26)00217-5", "scope": "Complete official correction notice read in a visible browser on the publisher site (open access); original title and PubMed ErratumIn linkage verified. Review limited to the notice.", "summary": "Only the Received date was corrected (to the original submission date of 26 April 2024). No result, data or abstract value was changed. The library cites the paper as the source of the MSK-IMPACT 50K data used in analysis A9." } }, { "type": "ErratumIn", "pmid": "42557769", "refSource": "Clin Transl Med. 2026 Aug;16(8):e70775. doi: 10.1002/ctm2.70775.", "forPmid": "42087741", "forKey": "P-PM42087741", "title": "Correction to \"Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2-overexpressing: Preliminary results of a prospective, single-arm, phase II study\".", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42557769/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42636841", "refSource": "Lancet Oncol. 2026 Sep;27(9):e404. doi: 10.1016/S1470-2045(26)00403-1.", "forPmid": "42134381", "forKey": "P-PM42134381", "title": "Correction to Lancet Oncol 2026; 27: 686-98.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42636841/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42721993", "refSource": "Lancet. 2026 Sep 12;408(10559):998. doi: 10.1016/S0140-6736(26)01822-2.", "forPmid": "42225112", "forKey": "P-PM42225112", "title": "Department of Error.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42721993/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42949732", "refSource": "JAMA Surg. 2026 Oct 28. doi: 10.1001/jamasurg.2026.5451.", "forPmid": "42384406", "forKey": "P-PM42384406", "title": "Error in Figure 2.", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42949732/", "unresolvedIdentifier": false, "reviewed": false }, { "type": "ErratumIn", "pmid": "42901850", "refSource": "Ann Oncol. 2026 Oct 20:S0923-7534(26)06772-4. doi: 10.1016/j.annonc.2026.09.013.", "forPmid": "42613139", "forKey": "P-RxPONDERAMH", "title": "Corrigendum to \"Ovarian reserve as a measure of adjuvant chemotherapy benefit in hormone receptor positive (HR-positive), HER2-negative, node-positive breast cancer in SWOG S1007 (RxPONDER)\": [Annals of Oncology 37 (2026) 1220-1229].", "text": "", "url": "https://pubmed.ncbi.nlm.nih.gov/42901850/", "unresolvedIdentifier": false, "reviewed": false } ] }, "panel": { "note": "Genes named in the gene column of the ESMO Precision Medicine Working Group 2024 NGS recommendations, tables 1, 3, 4 and 11 (ESCAT level I/II). Signatures (MSI-H/dMMR, TMB-H) are not genes and are not listed. Gastric cancer is covered only by Supplementary Table S2 of the same paper, which was not available when this list was made, so no gastric-specific genes are listed here. Structure Lab uses this list to group models; it does not make a model evidence. Genes in addedForPanel were added to the Structure Lab on 2026-10-05 because of this list alone; no evidence unit on this site is linked to them yet.", "source": { "citation": "Mosele MF et al. Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group. Ann Oncol 2024;35(7):588-606", "pmid": "38834388", "doi": "10.1016/j.annonc.2024.04.005", "url": "https://pubmed.ncbi.nlm.nih.gov/38834388/", "read": "2026-10-05, PDF supplied by the owner" }, "tables": { "agnostic": { "table": "Table 1", "label": "Tumour-agnostic", "genes": [ "NTRK1", "NTRK2", "NTRK3", "RET", "BRAF", "FGFR1", "FGFR2", "FGFR3" ] }, "breast": { "table": "Table 3", "label": "Breast", "genes": [ "ERBB2", "PIK3CA", "ESR1", "BRCA1", "BRCA2", "PTEN", "AKT1", "PALB2" ] }, "colorectal": { "table": "Table 4", "label": "Colorectal", "genes": [ "KRAS", "NRAS", "BRAF", "ERBB2", "POLE" ] }, "thyroid": { "table": "Table 11", "label": "Thyroid", "genes": [ "RET", "BRAF" ] } }, "noModel": { "BRCA2": "AlphaFold DB has no single model for P51587 (3418 residues); /api/prediction/P51587 returned 404 on 2026-10-05." }, "addedForPanel": [ "NTRK1", "NTRK2", "NTRK3", "FGFR1", "FGFR3", "PALB2", "KRAS", "NRAS", "POLE" ] }, "models": [ { "id": "AF-P04626-F1", "kind": "Predicted model", "label": 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