仑伐替尼联合帕博利珠单抗或依维莫司治疗晚期肾细胞癌。
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.
机构信息
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.).
出版信息
N Engl J Med. 2021 Apr 8;384(14):1289-1300. doi: 10.1056/NEJMoa2035716. Epub 2021 Feb 13.
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. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
背景
仑伐替尼联合帕博利珠单抗或依维莫司对晚期肾细胞癌具有活性。这些方案与舒尼替尼相比的疗效尚不清楚。
方法
在这项 3 期临床试验中，我们以 1:1:1 的比例随机分配（随机分配）未经系统治疗的晚期肾细胞癌患者接受仑伐替尼（20mg 口服，每日一次）加帕博利珠单抗（200mg 静脉注射，每 3 周一次），仑伐替尼（18mg 口服，每日一次）加依维莫司（5mg 口服，每日一次）或舒尼替尼（50mg 口服，每日一次，每 4 周接受治疗，2 周无治疗）。主要终点是无进展生存期，由独立审查委员会根据实体瘤反应评估标准 1.1 进行评估。还评估了总生存期和安全性。
结果
共有 1069 名患者被随机分配接受仑伐替尼加帕博利珠单抗（355 名）、仑伐替尼加依维莫司（357 名）或舒尼替尼（357 名）治疗。仑伐替尼加帕博利珠单抗组无进展生存期长于舒尼替尼组（中位无进展生存期：23.9 个月比 9.2 个月；疾病进展或死亡风险比：0.39；95%置信区间[CI]：0.32 至 0.49；P<0.001），仑伐替尼加依维莫司组也长于舒尼替尼组（中位无进展生存期：14.7 个月比 9.2 个月；风险比：0.65；95%CI：0.53 至 0.80；P<0.001）。仑伐替尼加帕博利珠单抗组总生存期长于舒尼替尼组（死亡风险比：0.66；95%CI：0.49 至 0.88；P=0.005），但仑伐替尼加依维莫司组与舒尼替尼组无差异（风险比：1.15；95%CI：0.88 至 1.50；P=0.30）。接受仑伐替尼加帕博利珠单抗治疗的患者中有 82.4%、接受仑伐替尼加依维莫司治疗的患者中有 83.1%和接受舒尼替尼治疗的患者中有 71.8%在治疗期间出现或恶化了 3 级或更高级别的不良事件。任何一组中至少 10%的患者出现的 3 级或更高级别的不良事件包括高血压、腹泻和脂肪酶水平升高。
结论
仑伐替尼加帕博利珠单抗与舒尼替尼相比，无进展生存期和总生存期显著延长。（由 Eisai 和 Merck Sharp and Dohme 资助；CLEAR ClinicalTrials.gov 编号，NCT02811861。）
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