Krishnansu S Tewari1, Bradley J Monk1, Ignace Vergote1, Austin Miller1, Andreia C de Melo1, Hee-Seung Kim1, Yong Man Kim1, Alla Lisyanskaya1, Vanessa Samouëlian1, Domenica Lorusso1, Fernanda Damian1, Chih-Long Chang1, Evgeniy A Gotovkin1, Shunji Takahashi1, Daniella Ramone1, Joanna Pikiel1, Beata Maćkowiak-Matejczyk1, Eva M Guerra Alía1, Nicoletta Colombo1, Yulia Makarova1, Danny Rischin1, Stephanie Lheureux1, Kosei Hasegawa1, Keiichi Fujiwara1, Jingjin Li1, Shaheda Jamil1, Vladimir Jankovic1, Chieh-I Chen1, Frank Seebach1, David M Weinreich1, George D Yancopoulos1, Israel Lowy1, Melissa Mathias1, Matthew G Fury1, Ana Oaknin1. 1. From the Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of California, Irvine, Orange (K.S.T.); the Division of Gynecologic Oncology, Arizona Oncology, University of Arizona, and Creighton University, Phoenix (B.J.M.); the Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium (I.V.); the Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo (A.M.) and Regeneron Pharmaceuticals, Tarrytown (J.L., S.J., V.J., C.-I.C., F.S., D.M.W., G.D.Y., I.L., M.M., M.G.F.) - both in New York; the Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro (A.C.M.), Centro de Pesquisa em Oncologia, Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre (F.D.), and the Department of Clinical Oncology, Barretos Cancer Hospital (Pio XII Foundation), São Paulo (D. Ramone) - all in Brazil; the Department of Obstetrics and Gynecology, Seoul National University College of Medicine (H.-S.K.), and the Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan (Y.M.K.) - both in Seoul, South Korea; St. Petersburg State Budgetary Institution of Health Care, St. Petersburg (A.L.), the State Budget Health Care Institution Ivanovo Regional Oncology Dispensary, Ivanovna (E.A.G.), and the State Budgetary Institution of Health Care, Clinical Oncology Dispensary No. 1, Krasnodar (Y.M.) - all in Russia; the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Centre Hospitalier de l'Université de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal (V.S.); the Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, and the Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome (D.L.); the Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and the Department of Medicine, Mackay Medical College, Taipei, Taiwan (C.-L.C.); the Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo (S.T.), and the Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka (K.H., K.F.) - both in Japan; the Department of Oncology, Szpitale Pomorskie, Gdynia (J.P.), and the Department of Gynecologic Oncology, Białostockie Centrum Onkologii, Białostockie (B.M.-M.) - both in Poland; the Department of Medical Oncology, Hospital Ramón y Cajal, Madrid (E.M.G.A.); the Department of Gynecologic Oncology, University of Milan-Bicocca and Istituto Europeo di Oncologia IRCCS, Milan (N.C.); the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (D. Rischin); the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto (S.L.); and the Gynecologic Cancer Program, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona (A.O.).
Abstract
BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).
BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).
Authors: Katrien Vandecasteele; Hannelore G Denys; Emiel A De Jaeghere; Sandra Tuyaerts; An M T Van Nuffel; Ann Belmans; Kris Bogaerts; Regina Baiden-Amissah; Lien Lippens; Peter Vuylsteke; Stéphanie Henry; Xuan Bich Trinh; Peter A van Dam; Sandrine Aspeslagh; Alex De Caluwé; Eline Naert; Diether Lambrechts; An Hendrix; Olivier De Wever; Koen K Van de Vijver; Frédéric Amant Journal: Cancer Immunol Immunother Date: 2022-08-12 Impact factor: 6.630