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仑伐替尼联合帕博利珠单抗或联合依维莫司治疗晚期肾细胞癌
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma


Robert Motzer ... 肿瘤 • 2021.04.08
相关阅读
• 肾细胞癌患者接受肾切除术后的帕博利珠单抗辅助治疗 • 晚期肾癌的新治疗方案 • 卡博替尼联合纳武利尤单抗延长了晚期肾癌患者的总生存期 • 转移性肾细胞癌的全身性治疗

摘要


背景

仑伐替尼联合帕博利珠单抗或联合依维莫司对晚期肾细胞癌均具有抗癌活性。上述两种方案与舒尼替尼的疗效比较尚未明确。

 

方法

在此项3期试验中,我们将未接受过全身性治疗的晚期肾细胞癌患者随机分组(比例为1∶1∶1),三组分别接受仑伐替尼(每日一次,每次口服20 mg)+帕博利珠单抗(每3周一次,每次静脉注射200 mg)、仑伐替尼(每日一次,每次口服18 mg)+依维莫司(每日一次,每次口服5 mg)或舒尼替尼(每日一次,每次口服50 mg;4周用药期和2周休药期交替)。主要终点是独立审查委员会根据《实体瘤疗效评价标准》(Response Evaluation Criteria in Solid TumorsRECIST)1.1版判定的无进展生存期。本试验还评估了总生存期和安全性。

 

结果

共计1,069例患者被随机分配接受仑伐替尼+帕博利珠单抗(355例患者)、仑伐替尼+依维莫司(357例)或舒尼替尼(357例)治疗。仑伐替尼+帕博利珠单抗组的无进展生存期超过舒尼替尼组(中位数,23.9个月 vs. 9.2个月;疾病进展或死亡的风险比,0.39;95%置信区间[CI],0.32~0.49;P<0.001),仑伐替尼+依维莫司组也超过舒尼替尼组(中位数,14.7个月 vs. 9.2个月;风险比,0.65;95% CI,0.53~0.80;P<0.001)。仑伐替尼+帕博利珠单抗组的总生存期超过舒尼替尼组(死亡的风险比,0.66;95% CI,0.49~0.88;P=0.005),但仑伐替尼+依维莫司组并未超过舒尼替尼组(风险比,1.15;95% CI,0.88~1.50;P=0.30)。仑伐替尼+帕博利珠单抗组82.4%的患者,仑伐替尼+依维莫司组83.1%的患者和舒尼替尼组71.8%的患者有治疗期间发生或恶化的3级或更高级别不良事件。见于任一组中至少10%患者的3级或更高级别不良事件包括高血压、腹泻和脂肪酶水平升高。

 

结论

仑伐替尼+帕博利珠单抗组的无进展生存期和总生存期均显著超过舒尼替尼组(由卫材和默沙东资助,CLEAR在ClinicalTrials.gov注册号为NCT02811861)。





作者信息

Robert Motzer, M.D., Boris Alekseev, M.D., Sun-Young Rha, M.D., Camillo Porta, M.D., Masatoshi Eto, M.D., Thomas Powles, M.D., Viktor Grünwald, M.D., Thomas E. Hutson, M.D., Evgeny Kopyltsov, M.D., María J. Méndez-Vidal, M.D., Vadim Kozlov, M.D., Anna Alyasova, M.D., Sung-Hoo Hong, M.D., Anil Kapoor, M.D., Teresa Alonso Gordoa, M.D., Jaime R. Merchan, M.D., Eric Winquist, M.D., Pablo Maroto, M.D., Jeffrey C. Goh, M.D., Miso Kim, M.D., Howard Gurney, M.B., B.S., Vijay Patel, M.D., Avivit Peer, M.D., Giuseppe Procopio, M.D., Toshio Takagi, M.D., Bohuslav Melichar, M.D., Frederic Rolland, M.D., Ugo De Giorgi, M.D., Shirley Wong, M.D., Jens Bedke, M.D., Manuela Schmidinger, M.D., Corina E. Dutcus, M.D., Alan D. Smith, M.D., Lea Dutta, M.D., Kalgi Mody, M.D., Rodolfo F. Perini, M.D., Dongyuan Xing, Ph.D., and Toni K. Choueiri, M.D. for the CLEAR Trial Investigators*
From Memorial Sloan Kettering Cancer Center, New York (R.M.); P. Hertsen Moscow Oncology Research Institute, Moscow (B.A.), the State Institution of Health Care Regional Clinical Oncology Dispensary, Omsk (E.K.), the State Budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk (V.K.), and Prevoljskiy Region Medical Center, Novgorod (A.A.) — all in Russia; Yonsei Cancer Center, Yonsei University Health System (S.Y.R.), Seoul St. Mary’s Hospital, Catholic University of Korea (S.-H.H.), and Seoul National University Hospital (M.K.), Seoul, South Korea; San Matteo University Hospital Foundation, Pavia (C.P.), Istituto Nazionale dei Tumori IRCCS, Milan (G.P.), and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola (U.D.G.) — all in Italy; Kyushu University, Fukuoka (M.E.), and Tokyo Women’s Medical University, Tokyo (T.T.) — both in Japan; the Royal Free NHS Trust, London (T.P.), and Eisai, Hatfield (A.D.S.) — both in the United Kingdom; University Hospital Essen, Essen (V.G.), and the University of Tübingen, Tübingen (J.B.) — both in Germany; Texas Oncology, Dallas (T.E.H.); Maimonides Institute for Biomedical Research of Cordoba Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba (M.J.M.-V.), Hospital Universitario Ramón y Cajal, Madrid (T.A.G.), and Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.) — all in Spain; McMaster University, Hamilton (A.K.), and Western University, London (E.W.) — both in Ontario, Canada; the University of Miami Sylvester Comprehensive Cancer Center, Miami (J.R.M.), and Florida Cancer Specialists, Gainesville (V.P.); ICON Research, South Brisbane, and University of Queensland, St. Lucia, QLD (J.C.G.), Macquarie University, Sydney (H.G.), and Western Health, Melbourne, VIC (S.W.) — all in Australia; Rambam Health Care Campus, Haifa, Israel (A.P.); Palacky University and University Hospital Olomouc, Olomouc, Czech Republic (B.M.); Centre René Gauducheau, Saint Herblain, France (F.R.); the Department of Urology, Medical University of Vienna, Vienna (M.S.); Eisai, Woodcliff Lake (C.E.D., L.D., K.M., D.X.), and Merck, Kenilworth (R.F.P.) — both in New Jersey; and Dana–Farber Cancer Institute, Boston (T.K.C.). Address reprint requests to Dr. Motzer at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, or at motzerr@mskcc.org; or to Dr. Choueiri at Dana–Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, or at toni_choueiri@dfci.harvard.edu. *A full list of the CLEAR Trial Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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