Dr Barber on the Significance of the KEYNOTE-775 Trial for the Second-line Treatment of Endometrial Cancer

Emma L. Barber, MD, assistant professor, Gynecologic Oncology, the Northwestern University Feinberg School of Medicine, director, Robotic Surgery, the Division of Gynecologic Oncology, Northwestern Medicine, discusses how key data from the phase 3 KEYNOTE-775 study (NCT03517449) improved the identification of patient populations within endometrial cancer that benefit from second-line immunotherapy.

The multicenter, randomized trial evaluated the efficacy of pembrolizumab (Keytruda) in combination with lenvatinib (Lenvima) for patients with advanced endometrial cancer who progressed on prior platinum-based chemotherapy, Barber begins. Patients were randomized to receive either the immune checkpoint inhibitor (ICI) combination or to physician's

choice of doxorubicin or paclitaxel. The trial specifically included patients with mismatch repair–proficient (pMMR) and mismatch repair–deficient (dMMR) disease. Notably, patients with pMMR typically experience poorer responses to ICI treatment, Barber states. The study's primary end points were progression-free survival (PFS) and overall survival (OS).

Results demonstrated that the combination significantly improved both median PFS and OS vs physician's choice of chemotherapy in the overall population, Barber reports. In the pMMR cohort, median PFS was 6.6 months and median OS was 17.4 months with pembrolizumab and lenvatinib. Comparatively, patients with pMMR in the chemotherapy arm achieved a median PFS of 3.8 months and median OS of 12 months. Regarding the regimen's safety profile, 88.9% of patients receiving the experimental regimen experienced grade 3 or higher adverse effects compared with 72.7% of those who received chemotherapy.

These findings revolutionized the treatment of endometrial cancer, Barber says. The previous standard of care (SOC) for patients without a biomarker was chemotherapy alone, she explains. However, this trial supported the use of ICI combinations as a new second-line SOC for patients in this population, regardless of their MMR expression, Barber concludes.