Dr Westin on the FDA Approval of Durvalumab Plus Chemo in dMMR Endometrial Cancer

Shannon Westin, MD, MPH, FACOG, director, Early Drug Development and Phase I Trials Department, professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the FDA approval of durvalumab (Imfinzi) with chemotherapy in mismatch repair deficient (dMMR) primary advanced or recurrent endometrial cancer.

On June 14, 2024, the FDA approved durvalumab in combination with carboplatin plus paclitaxel, followed by single-agent durvalumab, for this indication based on data from the phase 3 DUO-E trial (NCT04269200). In DUO-E, patients with dMMR tumors experienced a 64% reduction in disease progression risk with the addition of this PD-L1 inhibitor to standard-of-care (SOC) chemotherapy (HR, 0.42; 95% CI, 0.22-0.80), Westin reports. The median PFS was not reached (NR; 95% CI, NR-NR) for patients with dMMR tumors in the durvalumab arm compared with 7 months (95% CI, 6.7-14.8) for those in the placebo arm.

Although the overall population in the DUO-E trial showed a statistically significant improvement in PFS with the durvalumab regimen (HR, 0.71; 95% CI, 0.57-0.89; P = .003), it was noted that the benefit was primarily driven by patients with dMMR tumors. This conclusion was based on an exploratory analysis of mismatch repair (MMR) status, highlighting the importance of targeted therapy in this subset of patients.

The excitement surrounding this approval is substantial, especially considering the limited treatment options that were previously available for endometrial cancer, Westin explains. Prior to these recent advancements, there were no FDA-approved treatments specifically for this disease, she states. However, the recognition that checkpoint inhibition is an effective second-line strategy for recurrent dMMR endometrial cancer has led to significant progress. Accordingly, the DUO-E study aimed to capitalize on the efficacy of checkpoint inhibitors by incorporating them earlier in the treatment paradigm. Overall, the integration of durvalumab into a first-line treatment regimen provides a new SOC for patients with dMMR tumors.