TY - JOUR
T1 - Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma
AU - Motzer, R.
AU - Alekseev, B.
AU - Rha, S.-Y.
AU - Porta, C.
AU - Eto, M.
AU - Powles, T.
AU - Grünwald, V.
AU - Hutson, T. E.
AU - Kopyltsov, E.
AU - Méndez-Vidal, M. J.
AU - Kozlov, V.
AU - Alyasova, A.
AU - Hong, S.-H.
AU - Kapoor, A.
AU - Alonso Gordoa, T.
AU - Merchan, J. R.
AU - Winquist, E.
AU - Maroto, P.
AU - Goh, J. C.
AU - Kim, M.
AU - Gurney, H.
AU - Patel, V.
AU - Peer, A.
AU - Procopio, G.
AU - Takagi, T.
AU - Melichar, B.
AU - Rolland, F.
AU - de Giorgi, U.
AU - Wong, S.
AU - Bedke, J.
AU - Schmidinger, M.
AU - Dutcus, C. E.
AU - Smith, A. D.
AU - Dutta, L.
AU - Mody, K.
AU - Perini, R. F.
AU - Xing, D.
AU - Choueiri, T. K.
AU - CLEAR Trial Investigators
PY - 2021/4/8
Y1 - 2021/4/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103105017&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2035716
DO - 10.1056/NEJMoa2035716
M3 - Article
C2 - 33616314
AN - SCOPUS:85103105017
SN - 0028-4793
VL - 384
SP - 1289
EP - 1300
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 14
ER -