Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
复制标题
DOI：
10.1056/nejmoa1510665
复制
发表时间：
2015-11-05
期刊：
影响因子：
--
通讯作者：
CheckMate 025 Investigators
中科院分区：
文献类型：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
尼伏卢单抗是一种程序性死亡-1检查点抑制剂，在先前治疗的晚期肾癌患者的非对照研究中，显示出鼓舞人心的总存活率。这项随机开放的3期研究比较了尼伏卢单抗和依维莫司在肾癌前期治疗后的疗效。821例曾接受一种或两种抗血管生成治疗的晚期透明细胞肾癌患者被随机分为两组，尼伏单抗3 mg/kg，每2周一次静脉滴注，或伊维洛姆10 mg片剂，每日1次。主要终点是总体存活率。次要终点包括客观有效率和安全性。使用nivolumab的中位生存期(95%可信区间[CI])为25.0个月(21.8个月至不可估量)，而使用伊维洛单抗的总生存期为19.6个月(17.6~23.1个月)。尼伏卢单抗与依维莫司的死亡风险比为0.73(98.5%CI，0.57比0.93；P=0.0018)，符合预先定义的优势标准(P≤0.0148)。尼伏卢单抗的客观有效率(25%)高于伊波利姆(5%；优势比5.98；95%可信区间3.68至9.72；P<；0.001)。使用nivolumab的中位无进展生存期(95%CI)为4.6个月(3.7~5.4)，使用伊波利姆的中位无进展生存期为4.4个月(3.7~5.5)(风险比为0.88；95%CI为0.75~1.03；P=0.11)。与治疗相关的3级或4级不良事件发生在19%(Nivolumab)和37%(Everolimus)的患者中；最常见的是nivolumab引起的疲劳(3%)和evolimus引起的贫血(8%)。在有治疗经验的晚期肾癌患者中，尼伏卢单抗与伊波利姆相比，总体生存期更长，发生的3级或4级不良事件更少。ClinicalTrials.gov标识：NCT01668784
Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated encouraging overall survival in uncontrolled studies in previously treated patients with advanced renal cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in renal cell carcinoma after prior treatment. Eight hundred twenty-one patients with advanced clear-cell renal cell carcinoma previously treated with one or two antiangiogenic therapies were randomized (1:1) to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary end point was overall survival. Secondary end points included objective response rate and safety. Median (95% confidence interval [CI]) overall survival was 25.0 months (21.8 to not estimable) with nivolumab and 19.6 months (17.6 to 23.1) with everolimus. The hazard ratio for risk of death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.0018), meeting the predefined criterion for superiority (P≤0.0148). Objective response rate was greater with nivolumab (25%) than everolimus (5%; odds ratio 5.98; 95% CI, 3.68 to 9.72; P<0.001). Median (95% CI) progression-free survival was 4.6 months (3.7 to 5.4) with nivolumab and 4.4 months (3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% (nivolumab) and 37% (everolimus) of patients; most common was fatigue (3%) with nivolumab and anemia (8%) with everolimus. Overall survival was longer and fewer grade 3 or 4 adverse events occurred for nivolumab versus everolimus in treatment-experienced patients with advanced renal cell carcinoma. ClinicalTrials.gov Identifier: NCT01668784