[en] [en] BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.
METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.
RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.
CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
Disciplines :
Oncology
Author, co-author :
Motzer, Robert; Memorial Sloan Kettering Cancer Center, New York
Alekseev, Boris; P. Hertsen Moscow Oncology Research Institute, Moscow
Rha, Sun-Young; Yonsei Cancer Center, Yonsei University Health System
Porta, Camillo; San Matteo University Hospital Foundation, Pavia, Italy
Eto, Masatoshi; Kyushu University, Fukuoka,Tokyo
Powles, Thomas; the Royal Free NHS Trust, London, United Kingdom
Grünwald, Viktor; University Hospital Essen, Essen, Germany
Hutson, Thomas E; Texas Oncology, Dallas
Kopyltsov, Evgeny; State Institution of Health Care Regional Clinical Oncology Dispensary, Omsk, Russia
Méndez-Vidal, María J; Maimonides Institute for Biomedical Research of Cordoba Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba, Spain
Kozlov, Vadim; State Budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk, Russia
Alyasova, Anna; Prevoljskiy Region Medical Center, Novgorod, Russia
Hong, Sung-Hoo; Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, South Korea
Kapoor, Anil; McMaster University, Hamilton (A.K.), Ontario, Canada
Alonso Gordoa, Teresa; Hospital Universitario Ramón y Cajal, Madrid, Spain
Merchan, Jaime R; University of Miami Sylvester Comprehensive Cancer Center, Miami
Winquist, Eric; Western University, London, Ontario, Canada
Maroto, Pablo; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Goh, Jeffrey C; ICON Research, South Brisbane, and University of Queensland, St. Lucia, QLD, Australia
Kim, Miso; Seoul National University Hospital, Seoul, South Korea
Gurney, Howard; Macquarie University, Sydney, Australia
Patel, Vijay; Florida Cancer Specialists, Gainesville
Peer, Avivit; Rambam Health Care Campus, Haifa, Israel
Procopio, Giuseppe; Istituto Nazionale dei Tumori IRCCS, Milan
Takagi, Toshio; Tokyo Women's Medical University, Tokyo
Melichar, Bohuslav; Palacky University and University Hospital Olomouc, Olomouc, Czech Republic
Rolland, Frederic; Centre René Gauducheau, Saint Herblain, France
De Giorgi, Ugo ; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola
Wong, Shirley; Western Health, Melbourne, VIC, Australia
Bedke, Jens; University of Tübingen, Tübingen, Germany
Schmidinger, Manuela; Department of Urology, Medical University of Vienna, Vienna
Dutcus, Corina E; Eisai, Woodcliff Lake
Smith, Alan D; Eisai, Hatfield, United Kingdom
Dutta, Lea; Eisai, Woodcliff Lake
Mody, Kalgi; Eisai, Woodcliff Lake
Perini, Rodolfo F; Merck, Kenilworth
Xing, Dongyuan; Eisai, Woodcliff Lake
Choueiri, Toni K; Dana-Farber Cancer Institute, Boston
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