Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma Journal Article


Authors: Motzer, R.; Alekseev, B.; Rha, S. Y.; Porta, C.; Eto, M.; Powles, T.; Grünwald, V.; Hutson, T. E.; Kopyltsov, E.; Méndez-Vidal, M. J.; Kozlov, V.; Alyasova, A.; Hong, S. H.; Kapoor, A.; Alonso Gordoa, T.; Merchan, J. R.; Winquist, E.; Maroto, P.; Goh, J. C.; Kim, M.; Gurney, H.; Patel, V.; Peer, A.; Procopio, G.; Takagi, T.; Melichar, B.; Rolland, F.; de Giorgi, U.; Wong, S.; Bedke, J.; Schmidinger, M.; Dutcus, C. E.; Smith, A. D.; Dutta, L.; Mody, K.; Perini, R. F.; Xing, D.; Choueiri, T. K.; for the CLEAR Trial Investigators
Article Title: Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma
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. © 2021 Massachussetts Medical Society. All rights reserved.
Journal Title: New England Journal of Medicine
Volume: 384
Issue: 14
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2021-04-08
Start Page: 1289
End Page: 1300
Language: English
DOI: 10.1056/NEJMoa2035716
PUBMED: 33616314
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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  1. Robert Motzer
    1243 Motzer