Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial.
Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial.
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DOI：
10.1002/cncr.33033
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发表时间：
2020-09-15
期刊：
影响因子：
6.2
通讯作者：
Tannir NM
中科院分区：
文献类型：
--
作者：
Motzer RJ;Escudier B;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Plimack ER;Procopio G;McDermott DF;Castellano D;Choueiri TK;Donskov F;Gurney H;Oudard S;Richardet M;Peltola K;Alva AS;Carducci M;Wagstaff J;Chevreau C;Fukasawa S;Tomita Y;Gauler TC;Kollmannsberger CK;Schutz FA;Larkin J;Cella D;McHenry MB;Saggi SS;Tannir NM
CHECKMATE 025显示，在晚期肾细胞癌(ARCC)患者中，尼伏卢单抗的疗效优于埃博利姆，安全性和耐受性都有所提高。这项分析评估了nivolumab与everolimus的长期临床益处。这项随机、开放标签的3期CHECKMATE 025试验(NCT01668784)包括了以前接受过1-2种抗血管生成药物治疗的透明细胞型ARCC患者。患者被随机给予尼伏卢单抗3 mg/kg，q2w或伊维洛姆10 mg，qd，直到病情进展或出现不可接受的毒性。主要终点：总存活率(OS)。次要终点：确认的客观应答率(ORR)、无进展生存率(PFS)、安全性和健康相关的生活质量(HRQOL)。821例患者被随机分为尼伏卢单抗(n=410)和伊波利莫(n=411)；803例患者接受治疗--406例使用nivolumab，397例使用evolimus。在至少随访个月(中位数72个月)的情况下，尼伏卢单抗与依维莫司相比保持了OS益处(中位数[95%CI]25.8个月[22.2-29.8]比19.7个月[17.6-22.1]；HR，0.73[95%CI，0.62-0.85])，5年OS概率分别为26%和18%。使用nivolumab的ORR较高(94[23%]/410比17[4%]/411；P<；.001)。PFS也支持nivolumab(HR，0.84[95%CI，0.72-0.99]；P=0.0331)。与任何级别的治疗相关的最常见的不良反应是使用nivolumab时的乏力(34.7%)和瘙痒(15.5%)，以及使用依维莫司时的疲劳(34.5%)和口腔炎(29.5%)。服用nivolumab后，HRQOL较基线有所改善，但服用伊波利姆后，HRQOL保持不变或恶化。在没有新的安全信号的长期随访后，nivolumab保持了优于everolimus的疗效，支持了nivolumab单一疗法对以前治疗的ARCC患者的长期益处。Checkmate 025比较了nivolumab(一种新的免疫疗法)和everolimus(一种较老的护理标准疗法)对在抗血管生成治疗方面取得进展的晚期肾癌患者的疗效。经过5年的研究，nivolumab在延长患者的生命、提供对治疗的长期反应以及以可管理的安全性改善生活质量方面继续优于伊波利莫。结果表明，与以前治疗的晚期肾癌患者相比，尼伏卢单抗的临床益处将持续很长一段时间。CheckMate 025试验的5年随访分析结果表明，在以前治疗过的ARCC患者中，nivolumab的临床益处长期高于伊波利莫。使用nivolumab与everolimus相比，OS、PFS和ORR的益处保持不变，使用nivolumab治疗的患者更多地体验到改善的HRQOL，而nivolumab的安全性是可控的，与evolimus相比是有利的。
CheckMate 025 showed superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC), with improved safety and tolerability. This analysis assesses long-term clinical benefits of nivolumab versus everolimus. The randomized, open-label, phase 3 CheckMate 025 trial (NCT01668784) included patients with clear cell aRCC previously treated with 1–2 antiangiogenic regimens. Patients were randomized to nivolumab 3 mg/kg Q2W or everolimus 10 mg QD until progression or unacceptable toxicity. Primary endpoint: overall survival (OS). Secondary endpoints: confirmed objective response rate (ORR), progression-free survival (PFS), safety, and health-related quality of life (HRQoL). 821 patients were randomized to nivolumab (n=410) or everolimus (n=411); 803 patients were treated—406 with nivolumab and 397 with everolimus. With minimum follow-up of 64 months (median 72 months), nivolumab maintained an OS benefit versus everolimus (median [95% CI] 25.8 months [22.2–29.8] vs 19.7 months [17.6–22.1]; HR, 0.73 [95% CI, 0.62–0.85]), with 5-year OS probabilities of 26% and 18%, respectively. ORR was higher with nivolumab (94 [23%] of 410 vs 17 [4%] of 411; P<.001). PFS also favored nivolumab (HR, 0.84 [95% CI, 0.72–0.99]; P=0.0331). The most common any-grade treatment-related adverse events were fatigue (34.7%) and pruritus (15.5%) with nivolumab, and fatigue (34.5%) and stomatitis (29.5%) with everolimus. HRQoL improved versus baseline with nivolumab but remained the same or deteriorated with everolimus. The superior efficacy of nivolumab over everolimus was maintained after extended follow-up with no new safety signals, supporting the long-term benefits of nivolumab monotherapy in patients with previously treated aRCC. CheckMate 025 compared the effects of nivolumab (a novel immunotherapy) with everolimus (an older standard-of-care therapy) for the treatment of advanced kidney cancer in patients who had progressed on antiangiogenic therapy. After 5 years of study, nivolumab continues to be better than everolimus in extending the lives of patients, providing a long-lasting response to treatment and improving quality of life with a manageable safety profile. The results demonstrate that the clinical benefits with nivolumab compared with everolimus in previously treated patients with advanced kidney cancer continue in the long term. The results of the 5-year follow-up analysis of the CheckMate 025 trial demonstrate that the clinical benefits are sustained with nivolumab over everolimus in previously treated patients with aRCC in the long term. OS, PFS, and ORR benefits are maintained with nivolumab versus everolimus, and more patients treated with nivolumab experience an improved HRQoL, while the safety of nivolumab is manageable and compares favorably with everolimus.
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影响因子：
45.3
作者：
FYFE, G;FISHER, RI;LOUIE, AC
通讯作者：
LOUIE, AC
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
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
通讯作者：
CheckMate 025 Investigators
DOI：
10.1158/1078-0432.ccr-15-2839
发表时间：
2016-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Choueiri TK;Fishman MN;Escudier B;McDermott DF;Drake CG;Kluger H;Stadler WM;Perez-Gracia JL;McNeel DG;Curti B;Harrison MR;Plimack ER;Appleman L;Fong L;Albiges L;Cohen L;Young TC;Chasalow SD;Ross-Macdonald P;Srivastava S;Jure-Kunkel M;Kurland JF;Simon JS;Sznol M
通讯作者：
Sznol M
DOI：
10.1073/pnas.192461099
发表时间：
2002-09-17
影响因子：
11.1
作者：
Iwai, Y;Ishida, M;Minato, N
通讯作者：
Minato, N
影响因子：
4.5
作者：
Cella, David;Yount, Susan;Bro, William P.
通讯作者：
Bro, William P.