Latest analysis of the results from the phase III DUO-E trial showed durvalumab plus platinum-based chemotherapy followed by durvalumab plus olaparib demonstrated an improvement in multiple key secondary efficacy endpoints, particularly in patients with mismatch repair–proficient (pMMR) advanced or recurrent endometrial cancer, compared to chemotherapy alone. These results were presented in a late-breaking session at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.
Key Findings
A post hoc exploratory subgroup analysis assessed patients by mismatch repair (MMR) status, a biomarker of interest in endometrial cancer. In this analysis, median duration of response in pMMR patients in the durvalumab-plus-olaparib arm was more than double than that of the control arm (18.7 vs 7.6 months). Additional secondary endpoints showed consistent results for pMMR patients treated with durvalumab plus olaparib, demonstrating a reduction in the risk of second disease progression or death (PFS2) by 32% for the combination vs the control arm (median = not reached vs 19.5 months, hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.48–0.95), and improvement in time to first and second subsequent treatments.
Durvalumab plus chemotherapy followed by durvalumab monotherapy showed consistent benefit regardless of MMR status, with the greatest benefit observed in patients with mismatch repair–deficient (dMMR) disease across all secondary endpoints, including objective response rate (71.4%) and duration of response (median = not reached), vs the control arm (40.5% and 10.5 months, respectively).
In the overall trial population, results in the durvalumab-plus-olaparib arm showed extended objective response rate and duration of response, as well as consistently improved benefit in secondary endpoints, including overall survival, time to first subsequent therapy, PFS2, and time to second subsequent therapy.
‘Compelling Evidence’
Presenting author and DUO-E investigator Hye Sook Chon, MD, a gynecologic oncologist at the Moffitt Cancer Center, said, “Endometrial cancer diagnoses are rapidly rising, yet very little has changed in recent years to advance new treatments for the approximately 80% of patients with advanced or recurring disease who are pMMR. DUO-E results demonstrate the benefit of durvalumab plus chemotherapy followed by durvalumab for patients with dMMR status and provide compelling evidence for the addition of olaparib to this regimen for patients with pMMR status.”
Interim overall survival data showed a favorable trend for the durvalumab arm and the durvalumab-plus-olaparib arm compared to the control arm in the overall trial population, irrespective of MMR status. The safety profiles of both experimental regimens were manageable, well-tolerated, and broadly consistent with the known profiles of the individual agents.
