Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma

Robert Motzer, Boris Alekseev, Sun Young Rha, Camillo Porta, Masatoshi Eto, Thomas Powles, Viktor Grünwald, Thomas E. Hutson, Evgeny Kopyltsov, María J. Méndez-Vidal, Vadim Kozlov, Anna Alyasova, Sung Hoo Hong, Anil Kapoor, Teresa Alonso Gordoa, Jaime R. Merchan, Eric Winquist, Pablo Maroto, Jeffrey C. Goh, Miso KimHoward Gurney, Vijay Patel, Avivit Peer, Giuseppe Procopio, Toshio Takagi, Bohuslav Melichar, Frederic Rolland, Ugo de Giorgi, Shirley Wong, Jens Bedke, Manuela Schmidinger, Corina E. Dutcus, Alan D. Smith, Lea Dutta, Kalgi Mody, Rodolfo F. Perini, Dongyuan Xing, Toni K. Choueiri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1289-1300
Number of pages12
JournalNew England Journal of Medicine
Volume384
Issue number14
DOIs
StatePublished - Apr 8 2021

ASJC Scopus subject areas

  • Medicine(all)

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