Dr Powell on the Implications of the FDA Approval of Dostarlimab for Endometrial Cancer

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

On August 1, 2024, the FDA granted an expanded indication to dostarlimab in combination with carboplatin and paclitaxel, followed by dostarlimab maintenance monotherapy, for adult patients with primary advanced or recurrent endometrial cancer. The combination was initially approved in July 2023 for the treatment of patients with primary advanced or recurrent endometrial cancerthat is mismatch repair deficient or microsatellite instability–high as identified by an FDA-approved test. The expanded indication was supported by findings from part 1 of the phase 3 RUBY trial (NCT03981796). The RUBY trial revealed a significant improvement in overall survival with dostarlimab vs placebo in this patient population.

Recent treatment advancements have been limited in endometrial cancers, with only a few FDA approvals over the past 5 decades, Powell begins, stating that the availability of new treatment options is a welcome development for patients facing particularly aggressive forms of cancer. Notably, several studies now support using immunotherapy combined with chemotherapy in endometrial cancer, with the RUBY trial standing out due to its inclusion of patients with carcinosarcoma and those with slightly earlier disease stages compared with the patient population from the phase 3 NRG-GY018 trial (NCT03914612), which used pembrolizumab (Keytruda) under NCI sponsorship, he emphasizes.

The RUBY trial’s unique design offers insights specific to patients with carcinosarcoma and has influenced treatment recommendations, with carcinosarcoma being explicitly referenced in the National Comprehensive Cancer Network guidelines, Powell expands. For these cases, the guidelines recommend dostarlimab as the preferred treatment option, according to Powell. Although some distinctions exist among endometrial cancer research, recent studies collectively underscore the promise of immunotherapy-chemotherapy combinations in improving outcomes for patients with endometrial cancer, particularly aggressive subtypes like carcinosarcoma, he concludes.