Dr Westin on PFS Benefit With DUO-E Regimen Across Histologic and Molecular pMMR Endometrial Cancer Subgroups

“The take-home message is that there’s not a population, at least at this point, that we can tease out and [deem] the population that needs olaparib right now. It seems that benefit with [the addition of olaparib maintenance to durvalumab and chemotherapy] was observed across all the subgroups. I do think there’s a population that benefits more…[but] it has yet to be determined."

Shannon Westin, MD, MPH, FACOG, the director of Early Drug Development and the Phase I Trials Department, and a professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, at The University of Texas MD Anderson Cancer Center, discusses findings from a post hoc exploratory analysis of phase 3 DUO-E trial (NCT04269200) evaluating biomarker and histological heterogeneity, the presence of baseline ctDNA, and efficacy in patients with pMMR recurrent endometrial cancer receiving durvalumab (Imfinzi) with or without olaparib (Lynparza) plus chemotherapy.

Previously, the randomized, placebo-controlled, double-blind DUO-E study, which included patients with newly diagnosed stage III/IV or recurrent endometrial cancer and known mismatch repair status, met its dual primary end points of progression-free survival (PFS) within the intention-to-treat population with regard to chemotherapy plus durvalumab (n = 238) vs chemotherapy (n = 241) and chemotherapy plus durvalumab and olaparib (n = 239) vs chemotherapy. The respective hazard ratios in these two groups were 0.71 (95% CI, 0.57-0.89; P = .003) and 0.55 (95% CI, 0.43-0.69; P < .0001).

At the 2025 SGO Annual Meeting on Women’s Cancers, Westin shared findings from post hoc exploratory analyses of relevant clinical markers. In the subpopulation of patients with mismatch repair–proficient disease (n = 575), 84% were positive for at least one biomarker. The most prevalent biomarkers were PD-L1 positivity (67%) and TP53 mutations (59%), Westin said. She added that this was the population that had the highest level of molecular aberrations and that PD-L1 positivity and TP53 mutation status were concordant in about 44% of patients.

Moreover, 21% of patients had homologous recombination repair mutations and 8% had BRCA mutations. Twenty-seven percent of patients had serous tumors. According to Westin, TP53 mutations and serous-type cancer are often linked together, but that is not always the case. Several other histologies can also harbor TP53 mutations, which underscores that molecular assessments are needed just as much as pathologic assessments, she added.

Data showed that in the population with one of these molecular aberrations positive, the addition of durvalumab to chemotherapy led to a consistent benefit over chemotherapy alone. An additive potential PFS benefit with olaparib plus durvalumab/chemotherapy was also reported, and these benefits were observed across subtypes. To date, it is difficult to determine which population definitely needs olaparib, but Westin does think there is a population that benefits more. She concluded by saying that further studies are needed to elucidate the remaining questions.