Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.
The New England journal of medicine
oregon; portland; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Everolimus; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Phenylurea Compounds; Programmed Cell Death 1 Receptor; Progression-Free Survival; Protein Kinase Inhibitors; Quinolines; Sunitinib; Survival Analysis
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
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.).
Motzer, Robert; Alekseev, Boris; Rha, Sun-Young; Porta, Camillo; Eto, Masatoshi; Powles, Thomas; Grünwald, Viktor; Hutson, Thomas E; Kopyltsov, Evgeny; Méndez-Vidal, María J; Kozlov, Vadim; Alyasova, Anna; Hong, Sung-Hoo; Kapoor, Anil; Alonso Gordoa, Teresa; Merchan, Jaime R; Winquist, Eric; Maroto, Pablo; Goh, Jeffrey C; Kim, Miso; Gurney, Howard; Patel, Vijay; Peer, Avivit; Procopio, Giuseppe; Takagi, Toshio; Melichar, Bohuslav; Rolland, Frederic; De Giorgi, Ugo; Wong, Shirley; Bedke, Jens; Schmidinger, Manuela; Dutcus, Corina E; Smith, Alan D; Dutta, Lea; Mody, Kalgi; Perini, Rodolfo F; Xing, Dongyuan; Choueiri, Toni K; CLEAR Trial Investigators; and Curti (CLEAR Trial Investigators), Brendan, "Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma." (2021). Articles, Abstracts, and Reports. 4788.