V. Makker, N. Colombo, A. Casado Herráez, A.D. Santin, E. Colomba, D.S. Miller, K. Fujiwara, S. Pignata, S. Baron-Hay, I. Ray-Coquard, R. Shapira-Frommer, K. Ushijima, J. Sakata, K. Yonemori, Y.M. Kim, E.M. Guerra, U.A. Sanli, M.M. McCormack, A.D. Smith, S. Keefe, S. Bird, L. Dutta, R.J. Orlowski, D. Lorusso
BACKGROUND Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair–proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS A total of 827 patients (697 with pMMR disease and 130 with mismatch repair–deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. CONCLUSIONS Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309–KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.). Copyright © 2022 Massachusetts Medical Society.
Memorial Sloan Kettering Cancer Center, 300 E. 66th St., New York, 10065, NY, United States; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, United States; European Institute of Oncology IRCCS, University of Milan–Bicocca, Milan, Italy; Istituto Nazionale Tumori IRCCS–Fondazione G. Pascale, Naples, Italy; Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy; San Carlos University, Teaching Hospital, Philippines; Hospital Universitario Ramón y Cajal, Madrid, Spain; Yale University School of Medicine, New Haven, CT, United States; Gustave Roussy Cancerology Institute, Groupe d’Investigateurs Nationaux pour l’Étude des Cancers Ovariens (GINECO), Villejuif, France; Centre Léon-Bérard, University Claude Bernard, GINECO, Lyon, France; University of Texas Southwestern Medical Center, Dallas, United States; Saitama Medical University International Medical Center, Hidaka, Japan; Kurume University School of Medicine, Kurume, Japan; Aichi Cancer Center Hospital, Nagoya, Japan; National Cancer Center Hospital, Kokuritsu Gan Kenkyu Center Chuo Byoin, Tokyo, Japan; Royal North Shore Hospital, St. Leonards, NSW, Australia; Sheba Medical Center, Ramat Gan, Israel; Asan Medical Center, University of Ulsan, Seoul, South Korea; Ege University, Izmir, Turkey; University College London Hospitals, NHS Foundation Trust, London, United Kingdom; Eisai, Hatfield, United Kingdom; United Kingdom, Merck, Kenilworth, United Kingdom; Eisai, Woodcliff Lake, NJ, United States
