Biomarker heterogeneity and efficacy of durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib in patients with mismatch repair proficient endometrial cancer: exploratory analyses of the DUO-E/GOG-3041/ENGOT-EN10 trial.

The phase 3 DUO-E trial demonstrated statistically significant progression-free survival (PFS) benefit with carboplatin/paclitaxel plus durvalumab followed by durvalumab with/without olaparib maintenance versus carboplatin/paclitaxel alone in advanced/recurrent endometrial cancer. We report exploratory analyses of key biomarkers and histology in the mismatch repair proficient (pMMR) subpopulation. Patients were randomised 1:1:1 to carboplatin/paclitaxel (control arm), carboplatin/paclitaxel plus durvalumab followed by durvalumab (durvalumab arm) or carboplatin/paclitaxel plus durvalumab followed by durvalumab plus olaparib (durvalumab + olaparib arm). The presence of and relationship between selected biomarkers and histology, and PFS were investigated in the pMMR subpopulation. Biomarkers of interest (programmed death-ligand 1 [PD-L1] expression and mutations in BRCA1/BRCA2 genes, homologous recombination repair genes, DNA polymerase epsilon and tumour protein 53 [TP53m]) were evaluable in 486/575 patients in the pMMR subpopulation, with 84% (n = 407) positive for ≥ 1 biomarker; PD-L1 positive (67%) and TP53m (59%) were the most prevalent biomarkers. In the biomarker-known subpopulation, 52% and 27% of patients had tumours of endometrioid and serous histology, respectively. In exploratory analyses, PFS hazard ratios were improved versus control for both treatment arms across multiple biomarker and histology known subgroups, and favoured the durvalumab + olaparib arm in the majority of assessed biomarker/histological subgroups. The DUO-E pMMR subpopulation was highly heterogeneous with frequent overlap of biomarkers and histology. Consistent with the primary analysis, durvalumab plus olaparib improved the PFS benefit observed with durvalumab versus control across a range of biomarker and histological subgroups.