# Molecular-class-directed adjuvant therapy in endometrial cancer

Source: https://onco.cc/ideas/idea-molecular-class-adjuvant-endometrial/  
OnCo record `idea-molecular-class-adjuvant-endometrial` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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).
- Proposed test: RAINBO and PORTEC-4a read out 2027-2030; recurrence-free survival by class.
- Maturity: being-tested-at-scale

## Sources

- ClinicalTrials.gov NCT00411138: PORTEC-3: https://clinicaltrials.gov/study/NCT00411138

## Connected records

- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Endometrial cancer with no specific molecular profile](https://onco.cc/cancers/endometrial-nsmp/), [POLE-ultramutated endometrial cancer](https://onco.cc/cancers/endometrial-pole-ultramutated/)
- targets: [TP53](https://onco.cc/targets/tp53/)
- drugs: [Durvalumab](https://onco.cc/drugs/durvalumab/), [Olaparib](https://onco.cc/drugs/olaparib/), [Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)](https://onco.cc/drugs/megestrol-progestins/)
- terms: [Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)](https://onco.cc/terms/endometrial-molecular-classes/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- trials: [PORTEC-3](https://onco.cc/trials/portec-3/)
- key papers: [Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial](https://onco.cc/key-papers/paper-durvalumab-endometrial-j-immunother-cancer-2021/), [DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer](https://onco.cc/key-papers/paper-duo-e-jco-2023/), [Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)](https://onco.cc/key-papers/paper-durvalumab-endometrial-gynecol-oncol-2022/)

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