Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma
Por:
Motzer, R, Alekseev, B, Rha, SY, Porta, C, Eto, M, Powles, T, Grunwald, V, Hutson, TE, Kopyltsov, E, Mendez-Vidal, MJ, Kozlov, V, Alyasova, A, Hong, SH, Kapoor, A, Gordoa, TA, Merchan, JR, Winquist, E, Maroto, P, Goh, JC, 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, CE, Smith, AD, Dutta, L, Mody, K, Perini, RF, Xing, DY, Choueiri, TK, CLEAR Trial Investigators
Publicada:
8 abr 2021
Resumen:
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.
Filiaciones:
Motzer, R:
Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA
Alekseev, B:
P Hertsen Moscow Oncol Res Inst, Moscow, Russia
Rha, SY:
Yonsei Univ Hlth Syst, Yonsei Canc Ctr, Seoul, South Korea
Porta, C:
San Matteo Univ Hosp Fdn, Pavia, Italy
Eto, M:
Kyushu Univ, Fukuoka, Japan
Powles, T:
Royal Free NHS Trust, London, England
Grunwald, V:
Univ Hosp Essen, Essen, Germany
Hutson, TE:
Texas Oncol, Dallas, TX USA
Kopyltsov, E:
State Inst Hlth Care Reg Clin Oncol Dispensary, Omsk, Russia
Mendez-Vidal, MJ:
Univ Reina Sofia, Cordoba Hosp, Maimonides Inst Biomed Res, Dept Med Oncol, Cordoba, Spain
Kozlov, V:
State Budgetary Hlth Care Inst Novosibirsk Reg Cl, Novosibirsk, Russia
Alyasova, A:
Prevoljskiy Reg Med Ctr, Novgorod, Russia
Hong, SH:
Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea
Kapoor, A:
McMaster Univ, Hamilton, ON, Canada
Gordoa, TA:
Hosp Univ Ramon y Cajal, Madrid, Spain
Merchan, JR:
Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA
Winquist, E:
Western Univ, London, ON, Canada
Maroto, P:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Goh, JC:
ICON Res, South Brisbane, Qld, Australia
Univ Queensland, St Lucia, Qld, Australia
Kim, M:
Seoul Natl Univ Hosp, Seoul, South Korea
Gurney, H:
Macquarie Univ, Sydney, NSW, Australia
Patel, V:
Florida Canc Specialists, Gainesville, FL USA
Peer, A:
Rambam Hlth Care Campus, Haifa, Israel
Procopio, G:
Ist Nazl Tumori IRCCS, Milan, Italy
Takagi, T:
Tokyo Womens Med Univ, Tokyo, Japan
Melichar, B:
Palacky Univ, Olomouc, Czech Republic
Univ Hosp Olomouc, Olomouc, Czech Republic
Rolland, F:
Ctr Rene Gauducheau, St Herblain, France
De Giorgi, U:
Ist Sci Romagnolo Studio & Cura Tumori IRCCS, Meldola, Italy
Wong, S:
Western Hlth, Melbourne, Vic, Australia
Bedke, J:
Univ Tubingen, Tubingen, Germany
Schmidinger, M:
Med Univ Vienna, Dept Urol, Vienna, Austria
Dutcus, CE:
Eisai, Woodcliff Lake, NJ USA
Smith, AD:
Eisai, Hatfield, Herts, England
Dutta, L:
Eisai, Woodcliff Lake, NJ USA
Mody, K:
Eisai, Woodcliff Lake, NJ USA
Perini, RF:
Merck, Kenilworth, NJ USA
Xing, DY:
Eisai, Woodcliff Lake, NJ USA
Choueiri, TK:
Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA
Bronze
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