pairingsPairing
Chemotherapy + PD-1/PD-L1 blockade, first-line advanced endometrial cancer
Three trials with three different antibodies agree: adding immunotherapy to first chemotherapy for advanced endometrial cancer roughly triples progression-free time in dMMR tumours and helps the rest modestly.
RUBY (dostarlimab; OS 44.6 vs 28.2 months overall), NRG-GY018/KEYNOTE-868 (pembrolizumab; PFS HR 0.30 dMMR, 0.54 pMMR), DUO-E (durvalumab ± olaparib). The most consistent replication of any regimen in gynaecologic oncology.
Rationale
dMMR tumours carry thousands of neoantigens; chemotherapy provides antigen release and lymphodepletion that appear to extend benefit into pMMR disease.
Evidence
Three positive phase 3 trials; OS benefit shown in RUBY.