Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma Academic Article uri icon

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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. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

authors

  • 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

publication date

  • April 8, 2021

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