Dr Hinchcliff on the Benefits of Chemoimmunotherapy in Endometrial Cancer

“The key takeaways from any talk…about recent updates in endometrial cancer have to be the rapid expansion of treatment options, as well as the major effect that immunotherapy has had on our treatment regimens.”

Emily M. Hinchcliff, MD, MPH, assistant professor, Feinberg School of Medicine, Northwestern Medicine, discusses how the addition of immunotherapy to chemotherapy has affected the endometrial cancer treatment paradigm.

Recent advancements in endometrial cancer are indicative of the rapid growth of the treatment arsenal, particularly with the incorporation of immunotherapy into standard approaches, Hinchcliff begins. Since 2023, several randomized, controlled clinical trials, such as the phase 3 RUBY (NCT03981796) and KEYNOTE-868/NRG-GY018 (NCT03914612) studies, have shown the benefits of adding immunotherapy to chemotherapy and established that strategy as the standard of care for patients with endometrial cancer, she emphasizes.

On June 17, 2024, the FDA approved pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel, followed by pembrolizumab monotherapy, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma. In the pivotal KEYNOTE-868/NRG-GY018 trial, among patients with mismatch repair–deficient (dMMR) disease, the median progression-free survival (PFS) was not reached (NR; 95% CI, 30.7-NR) with pembrolizumab plus chemotherapy (n = 112); conversely, the median PFS was 6.5 months (95% CI, 6.4-8.7) with placebo plus chemotherapy (n = 113; HR, 0.30 [95% CI, 0.19-0.48]; P < .0001). Among patients with MMR-proficient disease, the median PFS was 11.1 months (95% CI, 8.7-13.5) in the pembrolizumab arm (n = 239) and 8.5 months (95% CI, 7.2-8.8) in the placebo arm (n = 295; HR, 0.60 [95% CI, 0.46-0.78]; P < .0001).

On August 1, 2024, the FDA approved dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel, followed by dostarlimab monotherapy, for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This regulatory decision expanded upon the July 2023 approval of the regimen for the treatment of adult patients with primary advanced or recurrent dMMR or microsatellite instability–high endometrial cancer. The expanded approval was supported by findings from part 1 of RUBY, in which patients in the overall population who received dostarlimab in combination with chemotherapy (n = 245) achieved a median overall survival of 44.6 months (95% CI, 32.6-NR) vs 28.2 months (95% CI, 22.1-35.6) with placebo plus chemotherapy (n = 249; HR, 0.69 [95% CI, 0.54-0.89]; 1-sided P = .002).