Endometrial carcinoma is one of the most common cancers among women worldwide. Due to the complexity of the disease, characterized by multiple risk factors and diverse histological and molecular subtypes, additional research remains necessary. The majority of patients (70–80%) have a pMMR phenotype and appear to derive additional benefit from adding anti-PD-(L)1 therapy to chemotherapy.
Patients newly diagnosed with stage III/IV or recurrent endometrial carcinoma who had not received prior systemic therapy were eligible for inclusion. Patients were randomized (1:1:1) to:
- 6 cycles of carboplatin/paclitaxel plus placebo followed by placebo maintenance therapy (placebo for both durvalumab and olaparib);
- 6 cycles of carboplatin/paclitaxel plus durvalumab followed by maintenance therapy with durvalumab plus olaparib placebo;
- 6 cycles of carboplatin/paclitaxel plus durvalumab followed by maintenance therapy with durvalumab plus olaparib.
The addition of durvalumab demonstrated a statistically significant improvement in progression-free survival compared with chemotherapy alone. This benefit was observed in both the dMMR and pMMR populations. In pMMR patients, adding olaparib to maintenance therapy provided an additional improvement in progression-free survival.
The addition of durvalumab to standard chemotherapy followed by maintenance therapy with durvalumab and olaparib may represent a major advancement in the current treatment of endometrial carcinoma.