{"entity":{"id":"idea-molecular-class-adjuvant-endometrial","kind":"idea","name":"Molecular-class-directed adjuvant therapy in endometrial cancer","aka":[],"tldr":"Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.","summary":"PORTEC-3 molecular analysis showed p53abn tumours gained the most from chemoradiation and POLEmut tumours nothing. The RAINBO programme (four parallel trials: p53abn-RED with olaparib, MMRd-GREEN with durvalumab, NSMP-ORANGE with progestin, POLEmut-BLUE de-escalation) and PORTEC-4a test this prospectively.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00411138: PORTEC-3","url":"https://clinicaltrials.gov/study/NCT00411138"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":["durvalumab","olaparib","megestrol-progestins"],"companies":[],"institutions":[],"pathways":[],"terms":["endometrial-molecular-classes","msi"],"trials":["portec-3"],"people":[],"bottlenecks":[],"keyPapers":["paper-duo-e-jco-2023","paper-durvalumab-endometrial-j-immunother-cancer-2021","paper-durvalumab-endometrial-gynecol-oncol-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Molecular-class-directed adjuvant therapy improves recurrence-free survival in p53abn and MMRd disease and safely omits adjuvant therapy in POLEmut disease compared with stage-based standard care.","rationale":"Retrospective PORTEC and TransPORTEC analyses consistently show class-specific benefit; the classifier is cheap (three IHC stains plus POLE sequencing).","test":"RAINBO and PORTEC-4a read out 2027-2030; recurrence-free survival by class.","maturity":"being-tested-at-scale"},"route":"/ideas/idea-molecular-class-adjuvant-endometrial/","neighbours":{"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-nsmp","kind":"cancer","name":"Endometrial cancer with no specific molecular profile","route":"/cancers/endometrial-nsmp/"},{"id":"endometrial-pole-ultramutated","kind":"cancer","name":"POLE-ultramutated endometrial cancer","route":"/cancers/endometrial-pole-ultramutated/"}],"target":[{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"megestrol-progestins","kind":"drug","name":"Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)","route":"/drugs/megestrol-progestins/"}],"term":[{"id":"endometrial-molecular-classes","kind":"term","name":"Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)","route":"/terms/endometrial-molecular-classes/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"portec-3","kind":"trial","name":"PORTEC-3","route":"/trials/portec-3/"}],"paper":[{"id":"paper-durvalumab-endometrial-j-immunother-cancer-2021","kind":"paper","name":"Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial","route":"/key-papers/paper-durvalumab-endometrial-j-immunother-cancer-2021/"},{"id":"paper-duo-e-jco-2023","kind":"paper","name":"DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer","route":"/key-papers/paper-duo-e-jco-2023/"},{"id":"paper-durvalumab-endometrial-gynecol-oncol-2022","kind":"paper","name":"Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)","route":"/key-papers/paper-durvalumab-endometrial-gynecol-oncol-2022/"}]}}