Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

被引：1256

作者：

Motzer, Robert ^{[1
]}

Alekseev, Boris ^{[2
]}

Rha, Sun-Young ^{[6
]}

Porta, Camillo ^{[9
]}

Eto, Masatoshi ^{[12
]}

Powles, Thomas ^{[14
]}

Gruenwald, Viktor ^{[16
]}

Hutson, Thomas E. ^{[18
]}

Kopyltsov, Evgeny ^{[3
]}

Mendez-Vidal, Maria J. ^{[19
]}

Kozlov, Vadim ^{[4
]}

Alyasova, Anna ^{[5
]}

Hong, Sung-Hoo ^{[7
]}

Kapoor, Anil ^{[22
]}

Alonso Gordoa, Teresa ^{[20
]}

Merchan, Jaime R. ^{[24
]}

Winquist, Eric ^{[23
]}

Maroto, Pablo ^{[21
]}

Goh, Jeffrey C. ^{[26
,27
]}

Kim, Miso ^{[8
]}

Gurney, Howard ^{[28
]}

Patel, Vijay ^{[25
]}

Peer, Avivit ^{[30
]}

Procopio, Giuseppe ^{[10
]}

Takagi, Toshio ^{[13
]}

Melichar, Bohuslav ^{[31
,32
]}

Rolland, Frederic ^{[33
]}

De Giorgi, Ugo ^{[11
]}

Wong, Shirley ^{[29
]}

Bedke, Jens ^{[17
]}

Schmidinger, Manuela ^{[34
]}

Dutcus, Corina E. ^{[35
]}

Smith, Alan D. ^{[15
]}

Dutta, Lea ^{[35
]}

Mody, Kalgi ^{[35
]}

Perini, Rodolfo F. ^{[36
]}

Xing, Dongyuan ^{[35
]}

Choueiri, Toni K. ^{[37
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[2] P Hertsen Moscow Oncol Res Inst, Moscow, Russia

[3] State Inst Hlth Care Reg Clin Oncol Dispensary, Omsk, Russia

[4] State Budgetary Hlth Care Inst Novosibirsk Reg Cl, Novosibirsk, Russia

[5] Prevoljskiy Reg Med Ctr, Novgorod, Russia

[6] Yonsei Univ Hlth Syst, Yonsei Canc Ctr, Seoul, South Korea

[7] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea

[8] Seoul Natl Univ Hosp, Seoul, South Korea

[9] San Matteo Univ Hosp Fdn, Pavia, Italy

[10] Ist Nazl Tumori IRCCS, Milan, Italy

[11] Ist Sci Romagnolo Studio & Cura Tumori IRCCS, Meldola, Italy

[12] Kyushu Univ, Fukuoka, Japan

[13] Tokyo Womens Med Univ, Tokyo, Japan

[14] Royal Free NHS Trust, London, England

[15] Eisai, Hatfield, Herts, England

[16] Univ Hosp Essen, Essen, Germany

[17] Univ Tubingen, Tubingen, Germany

[18] Texas Oncol, Dallas, TX USA

[19] Univ Reina Sofia, Cordoba Hosp, Maimonides Inst Biomed Res, Dept Med Oncol, Cordoba, Spain

[20] Hosp Univ Ramon y Cajal, Madrid, Spain

[21] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[22] McMaster Univ, Hamilton, ON, Canada

[23] Western Univ, London, ON, Canada

[24] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA

[25] Florida Canc Specialists, Gainesville, FL USA

[26] ICON Res, South Brisbane, Qld, Australia

[27] Univ Queensland, St Lucia, Qld, Australia

[28] Macquarie Univ, Sydney, NSW, Australia

[29] Western Hlth, Melbourne, Vic, Australia

[30] Rambam Hlth Care Campus, Haifa, Israel

[31] Palacky Univ, Olomouc, Czech Republic

[32] Univ Hosp Olomouc, Olomouc, Czech Republic

[33] Ctr Rene Gauducheau, St Herblain, France

[34] Med Univ Vienna, Dept Urol, Vienna, Austria

[35] Eisai, Woodcliff Lake, NJ USA

[36] Merck, Kenilworth, NJ USA

[37] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 384卷 / 14期

关键词：

1ST-LINE TREATMENT; FOLLOW-UP; SUNITINIB; CABOZANTINIB; MONOTHERAPY; THERAPY; CANCER; TRIAL;

D O I：

10.1056/NEJMoa2035716

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1289 / 1300

页数：12

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