Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Treated Beyond Progression: A Subgroup Analysis of a Randomized Clinical Trial.
Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Treated Beyond Progression: A Subgroup Analysis of a Randomized Clinical Trial.
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Nivolumab对超出进展的转移性肾细胞癌患者的安全性和功效：对随机临床试验的亚组分析。
DOI：
10.1001/jamaoncol.2016.0775
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发表时间：
2016-09-01
期刊：
影响因子：
28.4
通讯作者：
Rini BI
中科院分区：
文献类型：
--
作者：
George S;Motzer RJ;Hammers HJ;Redman BG;Kuzel TM;Tykodi SS;Plimack ER;Jiang J;Waxman IM;Rini BI
免疫治疗的反应模式可能与其他治疗不同。这需要进一步的研究，因为一些患者可能从持续的免疫治疗中获益，超过实体瘤反应评估标准（RECIST）定义的首次进展。为了评估nivolumab（一种程序性细胞死亡1免疫检查点抑制剂）治疗转移性肾细胞癌（mRCC）患者的安全性和潜在益处，超过研究者评估的首次进展。2011年5月31日启动的一项盲法、随机、多中心、2期剂量范围试验的亚组分析，包括先前接受抗血管生成治疗的透明细胞mRCC患者。该亚组分析的数据截止日期为2013年5月15日（无进展生存期和客观缓解率）和2014年3月5日（总生存期和缓解持续时间）。在该分析中，在首次进展后接受治疗的患者在recist定义的进展后6周以上接受了最后一次纳武单抗剂量，而未在首次进展后接受治疗的患者在recist定义的进展前或进展时停用了纳武单抗。尼武单抗0.3、2或10mg /kg静脉注射，每3周一次。纳武单抗治疗的安全性和有效性。168例患者（年龄中位数为61岁[37-81]岁，72%为男性）随机分到尼武单抗组，154例出现进展（36例治疗超过首次进展，26例治疗超过首次进展≤6周，92例未超过首次进展），13例接受治疗且未出现进展，1例未接受治疗。在首次进展之前，recist定义的客观缓解率为14%（5例）和16%（15例），治疗和未治疗超过进展的患者的中位无进展生存期分别为4.2 （95% CI, 2.8-5.5）和2.6 （95% CI, 1.5-3.9）个月。在最初的进展之后，25例（69%）治疗超过进展的患者随后经历了肿瘤缩小或目标病变大小稳定。超过进展期接受治疗的患者（n = 29[81%]）与未超过进展期接受治疗的患者（n = 61[66%]）相比，治疗相关不良事件的发生率更高；然而，在调整治疗暴露时间后，进展后接受治疗的患者的发病率较低（治疗与未接受治疗的进展后患者的发病率分别为322.9 vs 518.7 /100患者-年）。在这一亚组分析中，超过recist定义的首次进展继续治疗的患者比例显示肿瘤负担持续减少或目标病变大小稳定，具有可接受的安全性。进一步的分析将有助于确定纳武单抗治疗mRCC患者的临床获益。
Response patterns with immunotherapy may differ from those of other treatments. This warrants further investigation because some patients may benefit from continued immunotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)-defined first progression. To evaluate the safety and potential benefit of treatment with nivolumab, a programmed cell death 1 immune checkpoint inhibitor, beyond investigator-assessed first progression in patients with metastatic renal cell carcinoma (mRCC). Subgroup analysis of a blinded, randomized, multicenter, phase 2 dose-ranging trial initiated May 31, 2011, including patients with clear-cell mRCC previously treated with antiangiogenic therapy. Data cutoffs for this subgroup analysis were May 15, 2013, for progression-free survival and objective response rate and March 5, 2014, for overall survival and duration of response. In this analysis, patients treated beyond first progression received their last dose of nivolumab more than 6 weeks after RECIST-defined progression, and patients not treated beyond first progression discontinued nivolumab before or at RECIST-defined progression. Nivolumab 0.3, 2, or 10 mg/kg intravenously every 3 weeks. Safety and efficacy of nivolumab treatment. Of 168 patients (median [range] age, 61 [37–81] years; 72% male) randomized to nivolumab, 154 experienced progression (36 were treated beyond first progression, 26 were treated beyond first progression for ≤ 6 weeks, and 92 were not treated beyond first progression), 13 were treated and did not experience progression, and 1 was not treated. Prior to first progression, the RECIST-defined objective response rate was 14% (5 patients) and 16% (15 patients), and median progression-free survival was 4.2 (95% CI, 2.8–5.5) and 2.6 (95% CI, 1.5–3.9) months in patients treated and not treated beyond progression, respectively. Following initial progression, 25 (69%) patients treated beyond progression experienced subsequent tumor reduction or stabilization in target lesion size. The incidence of treatment-related adverse events was higher in patients treated beyond progression (n = 29 [81%]) vs those not treated beyond progression (n = 61 [66%]); however, after adjusting for length of treatment exposure, incidence was lower in patients treated beyond progression (322.9 vs 518.7 incidence rate/100 patient-years for patients treated vs not treated beyond progression). In this subgroup analysis, a proportion of patients who continued treatment beyond RECIST-defined first progression demonstrated sustained reductions in tumor burden or stabilization in the size of target lesions, with an acceptable safety profile. Further analysis will help define the clinical benefit for patients with mRCC treated with nivolumab beyond progression.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
--
作者：
Raman R;Vaena D
通讯作者：
Vaena D
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
影响因子：
45.3
作者：
Osoba, D;Tannock, IF;Neville, AJ
通讯作者：
Neville, AJ
影响因子：
3.7
作者：
KAPLAN, EL;MEIER, P
通讯作者：
MEIER, P