Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy in metastatic renal cell carcinoma: A meta-analysis.
Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy in metastatic renal cell carcinoma: A meta-analysis.
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DOI：
10.1002/cam4.4587
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发表时间：
2022-04
期刊：
影响因子：
4
通讯作者：
Yin M
中科院分区：
文献类型：
--
作者：
Yang Y;Mori SV;Li M;Hinkley M;Parikh AB;Collier KA;Miah A;Yin M
抗PD-1/PD-L1治疗后挽救nivolumab和ipilimumab经常用于透明细胞转移性肾细胞癌(MRCC)的非标签治疗。然而，指导这种治疗的数据有限。我们进行了一项荟萃分析，以进一步表征挽救治疗的nivolumab和ipilimumab的安全性和有效性。我们根据PRISMA进行了系统的审查。纳入2021年6月1日之前发表在英文版的有关抢救性治疗肾细胞癌患者的nivolumab和ipilimumab的研究。我们还通过回顾图表纳入了2012至2020年间在俄亥俄州立大学接受治疗的患者。纳入的研究根据其设计进一步分为适应性组和标准组。我们通过汇集数据和使用STATA Metaprop程序进行定量合成来计算客观应答率(ORR)和不良事件(AEs)。采用保守随机效应模型进行数值组合。共纳入7项研究和310名患者。挽救的nivolumab和ipilimumab的ORR为14%(95%CI，0.09-0.21)，中位无进展生存期为3.7-5.5个月。七项研究中有四项是标准设计，而其他三项研究是适应性研究。与适应性组(分别为21%和9%-10%)相比，标准组的ORR在数值上更高。挽救nivolumab和ipilimumab的应答与最初的抗PD-1/PD-L1应答无关(优势比t=1.45；p=0.50)。≥3级AEs发生率为2 6%(95%CI，0.19~0.33)。在这项研究中没有观察到新的安全信号。在既往接受抗PD-1/PD-L1治疗的肾细胞癌患者中，补救的nivolumab和ipilimumab显示出中等的抗肿瘤活性和可控的安全性。转移性肾癌患者在接受抗PD-1/PD-L1治疗的进展性疾病后，治疗选择有限。挽救尼伏卢单抗和伊普利单抗在该患者群体中的作用尚不明确。对这一高度重要和临床相关的主题的研究因样本量小而受到限制。我们的荟萃分析结果表明，nivolumab和ipilimumab在抢救环境中是可行的，具有中等的疗效和可接受的毒性。不同的治疗设计有不同的有效率。这些信息将有助于指导临床决策和准确估计毒性。进展性疾病后挽救nivolumab和ipilimumab在抗PD-1/PD-L1治疗中的作用尚不清楚。对这一高度重要和临床相关的主题的研究因样本量小而受到限制。我们的荟萃分析结果表明，nivolumab和ipilimumab在抢救环境中是可行的，具有中等的疗效和可接受的毒性。不同的治疗设计有不同的有效率。
Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy is frequently used off‐label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available to guide such therapy. We performed a meta‐analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab. We conducted a systematic review in accordance with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review. The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values. A total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09–0.21) and median progression‐free survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9–10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti‐PD‐1/PD‐L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19–0.33). There were no new safety signals observed in this study. Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti‐PD‐1/PD‐L1 therapy. Patients with metastatic renal cell carcinoma have limited treatment options after progressive disease on anti‐PD‐1/PD‐L1 therapy. The role of salvage nivolumab and ipilimumab in this patient population is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs. This information will be beneficial to guide clinical decision‐making and accurately estimating toxicity. The role of salvage nivolumab and ipilimumab after progressive disease on anti‐PD‐1/PD‐L1 therapy is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs.
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影响因子：
50.3
作者：
Arce Vargas F;Furness AJS;Litchfield K;Joshi K;Rosenthal R;Ghorani E;Solomon I;Lesko MH;Ruef N;Roddie C;Henry JY;Spain L;Ben Aissa A;Georgiou A;Wong YNS;Smith M;Strauss D;Hayes A;Nicol D;O'Brien T;Mårtensson L;Ljungars A;Teige I;Frendéus B;TRACERx Melanoma;TRACERx Renal;TRACERx Lung consortia;Pule M;Marafioti T;Gore M;Larkin J;Turajlic S;Swanton C;Peggs KS;Quezada SA
通讯作者：
Quezada SA
影响因子：
45.3
作者：
Gul, Anita;Stewart, Tyler F.;Rini, Brian I.
通讯作者：
Rini, Brian I.
晚期肾细胞癌中 Nivolumab 和 Ipilimumab 的优化治疗：基于反应的 II 期研究 (OMNIVORE)
影响因子：
45.3
作者：
McKay, Rana R.;McGregor, Bradley A.;Choueiri, Toni K.
通讯作者：
Choueiri, Toni K.
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：
10.1016/s1470-2045(21)00241-2
发表时间：
2021-07
期刊：
The Lancet. Oncology
影响因子：
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作者：
Lee CH;Shah AY;Rasco D;Rao A;Taylor MH;Di Simone C;Hsieh JJ;Pinto A;Shaffer DR;Girones Sarrio R;Cohn AL;Vogelzang NJ;Bilen MA;Gunnestad Ribe S;Goksel M;Tennøe ØK;Richards D;Sweis RF;Courtright J;Heinrich D;Jain S;Wu J;Schmidt EV;Perini RF;Kubiak P;Okpara CE;Smith AD;Motzer RJ
通讯作者：
Motzer RJ