Molecular classification of the PORTEC-3 trial: prognosis and benefit from adjuvant chemotherapy by molecular group
Re-analysing the PORTEC-3 trial by molecular class showed that p53-abnormal endometrial cancers gained substantially from adding chemotherapy to radiotherapy, POLE-mutated tumours did well regardless, and the other groups gained little.
Overview
Molecular classification of 410 high-risk endometrial cancers from the PORTEC-3 trial (chemoradiotherapy versus radiotherapy) into p53-abnormal, POLE-mutated, mismatch repair-deficient and no specific molecular profile groups.
Five-year recurrence-free survival for p53-abnormal tumours was 59 percent with chemoradiotherapy against 36 percent with radiotherapy alone; POLE-mutated tumours had 96 to 100 percent recurrence-free survival in both arms; mismatch repair-deficient and no specific molecular profile groups showed no significant benefit from chemotherapy.
- p53-abnormal: five-year recurrence-free survival 59 percent vs 36 percent with chemoradiotherapy vs radiotherapy.
- POLE-mutated: recurrence-free survival 96 to 100 percent regardless of treatment.
Molecular class is now a predictive factor for adjuvant therapy: chemotherapy for p53-abnormal disease, de-escalation for POLE-mutated tumours, and trials of immunotherapy for mismatch repair-deficient disease.
- Retrospective subgroup analysis with small molecular groups.
- Confirmation is being sought in the RAINBO programme.
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