Dr Powell on the FDA Approval of Dostarlimab Plus Chemo in Advanced/Recurrent Endometrial Cancer

Matthew Powell, MD, the Ira C. and Judith Gall Distinguished Professor of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, discusses the implications of the FDA approval of dostarlimab-gxly (Jemperli) plus chemotherapy for patients with advanced or recurrent endometrial cancer.

On August 1, 2024, the regulatory agency approved an expanded indication for dostarlimab in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab maintenance, for the treatment adult patients with primary advanced or recurrent endometrial cancer. The combination, followed by dostarlimab monotherapy, was initially approved in July 2023 for patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability high (MSI-H).

The intial approval and expanded indication were based on findings from part 1 of the phase 3 RUBY trial (NCT03981796), which Powell explains demonstrated a significant overall survival (OS) benefit in a patient population that have seen few advancements in treatment options over the past two decades. In the overall population enrolled in RUBY, the addition of dostarlimab to standard chemotherapy resulted in a 31% reduction in the risk of death compared with chemotherapy plus placebo (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002). Patients who received the combination (n = 245) achieved a median OS of 44.6 months (95% CI, 32.6–not reached [NR]) vs 28.2 months (95% CI, 22.1-35.6) for those given chemotherapy plus placebo (n = 249).

Powell notes that the benefit of dostarlimab plus chemotherapy was observed across different subgroups, including patients with dMMR or mismatch repair–proficient (pMMR) disease, which supported the expanded indication.

Results showed that for patients with dMMR/MSI-H tumors, the median OS was NR (95% CI, NR-NR) in the dostarlimab arm (n = 53) compared with 31.4 months (95% CI, 20.3-NR) in the placebo arm (n = 65; HR, 0.32; 95% CI, 0.166-0.629). In those with pMMR tumors, the median OS was 34.0 months (95% CI, 28.6-NR) for the dostarlimab arm (n = 192) vs 27.0 months (95% CI, 21.5-35.6) in the placebo arm (n = 184; HR, 0.79; 95% CI, 0.602-1.044).