According to exploratory analyses from the phase 3 DUO-E trial, durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib improved the progression-free survival (PFS) across multiple molecular, histological, and ctDNA-defined subgroups among patients with newly diagnosed stage III/IV or recurrent endometrial cancer.

These results were first presented by Kathleen Moore, MD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, at the 2025 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

It has previously been reported that the phase 3 DUO-E trial found a benefit to PFS with carboplatin/paclitaxel plus durvalumab followed by durvalumab with or without olaparib when compared with carboplatin/paclitaxel alone, among patients with endometrial cancer. While the greatest benefit with chemotherapy plus durvalumab followed by durvalumab alone was among those patients with mismatch repair deficient (dMMR) disease, the addition of olaparib maintenance further improved this benefit among patients with pMMR disease.

These exploratory analyses evaluate the efficacy among those patients with pMMR disease by biomarker, histological, and ctDNA-defined subgroups (PD-L1 status; POLE, TP53, HRR, and BRCA1/2 mutation status; histological subtype; baseline ctDNA detection status).

There were 575 patients in the pMMR subpopulation of the DUO-E trial, 486 if which had samples evaluable for PD-L1, BRCA, HRR, POLE, TP53, and histology. Dr Moore et al noted, “this subpopulation was heterogeneous with frequent overlap of biomarkers,” with 84% of patients in this subpopulation positive from ≥1 biomarker. Baseline ctDNA profiling was performed on 284 patients in the pMMR subpopulation with 79% of those patients showing detectable ctDNA. Across all 575 patients, PFS benefit was seen with chemotherapy plus durvalumab vs chemotherapy alone among many subgroups. With olaparib added to maintenance, the PFS benefit was further improved across multiple subgroups including PD-L1 positive, TP53 mutated, serous histology, and those with detectable baseline ctDNA.
Dr Moore et al concluded, “The pMMR population was highly heterogeneous; adding olaparib maintenance to [carboplatin/paclitaxel] plus durvalumab enhanced the PFS benefit observed across a range of biomarker and histological subgroups.”

Source:

Moore K, Westin SN, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with/without olaparib in endometrial cancer: Biomarkers, histological heterogeneity, baseline circulating tumor DNA, and efficacy in the DUO-E mismatch repair proficient subpopulation. Presented at the 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, WA. Abstract 939696.