临床试验中免疫检查点抑制剂与治疗相关的严重不良事件：一项系统评价
Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review.
作者信息
Ouyang Tao, Cao Yanyan, Kan Xuefeng, Chen Lei, Ren Yanqiao, Sun Tao, Yan Liangliang, Xiong Bin, Liang Bin, Zheng Chuansheng
机构信息
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
出版信息
Front Oncol. 2021 May 11;11:621639. doi: 10.3389/fonc.2021.621639. eCollection 2021.
BACKGROUND
Immune Checkpoint Inhibitors (ICI) have been progressively used in cancer treatment and produced unique toxicity profiles. This systematic review aims to comprehend the patterns and occurrence of treatment-related adverse events (trAEs) based on ICI.
METHODS
PICOS/PRISMA methods were used to identify published English-language on PubMed, Web of Science, and Scopus from 2015 to 2020. Published clinical trials on ICI monotherapy, combined ICIs, and ICI plus other treatment with tabulated data on grade≥3 trAEs were included. Odds ratio (OR), χ tests were used to analyze for effect size and associations.
RESULTS
This review included 145 clinical trials involving 21786 patients. Grade 3-5 trAEs were more common with ICI when they were plused with other treatments compared with ICI monotherapy(54.3% versus 17.7%, 46.1%, <0.05). Grade 3-5 trAEs were also more common with CTLA-4 mAbs compared with anti-PD-1 and anti-PD-L1 (34.2% versus 15.1%, 13.6%, <0.05). Hyperthyroidism (OR 3.8, 95%CI 1.7-8.6), nausea (OR 3.7, 95%CI 2.5-5.3), diarrhea (OR 2.7, 95%CI 2.2-3.2), colitis (OR 3.4, 95%CI 2.7-4.3), ALT increase (OR 4.9, 95%CI 3.9-6.1), AST increase (OR 3.8, 95%CI 3.0-4.9), pruritus (OR 2.4, 95%CI 1.5-3.9), rash (OR 2.8, 95%CI 2.1-3.8), fatigue (OR 2.8, 95%CI 2.2-3.7), decreased appetite (OR 2.4, 95%CI 1.5-3.8), and hypophysitis (OR 2.0, 95%CI 1.2-3.3) were more frequent with combined ICIs. Diarrhea (OR 8.1, 95%CI 6.4-10.3), colitis (OR 12.2, 95%CI 8.7-17.1), ALT increase (OR 5.1, 95%CI 3.5-7.4), AST increase (OR 4.2, 95%CI 2.8-6.3), pruritus (OR 4.1, 95%CI 2.0-8.4), rash (OR 4.4, 95%CI 2.9-6.8), hypophysitis (OR 12.1, 95%CI 6.3-23.4) were more common with CTLA-4 mAbs; whereas pneumonitis (OR 4.7, 95% CI 2.1-10.3) were more frequent with PD-1 mAbs.
CONCLUSIONS
Different immune checkpoint inhibitors are associated with different treatment-related adverse events profiles. A comprehensive data in this systematic review will provide comprehensive information for clinicians.
背景
免疫检查点抑制剂（ICI）已逐渐应用于癌症治疗，并产生了独特的毒性特征。本系统评价旨在了解基于ICI的治疗相关不良事件（trAE）的模式和发生率。
方法
采用PICOS/PRISMA方法，在PubMed、Web of Science和Scopus上检索2015年至2020年发表的英文文献。纳入已发表的关于ICI单药治疗、联合ICI以及ICI联合其他治疗且有≥3级trAE列表数据的临床试验。采用比值比（OR）、χ检验分析效应大小和相关性。
结果
本评价纳入145项临床试验，涉及21786例患者。与ICI单药治疗相比，ICI联合其他治疗时3 - 5级trAE更常见（54.3%对17.7%、46.1%，P<0.05）。与抗PD - 1和抗PD - L1相比，CTLA - 4单克隆抗体治疗时3 - 5级trAE也更常见（34.2%对15.1%、13.6%，P<0.05）。联合ICI时，甲状腺功能亢进（OR 3.8，95%CI 1.7 - 8.6）、恶心（OR 3.7，95%CI 2.5 - 5.3）、腹泻（OR 2.7，95%CI 2.2 - 3.2）、结肠炎（OR 3.4，95%CI 2.7 - 4.3）、谷丙转氨酶升高（OR 4.9，95%CI 3.9 - 6.1）、谷草转氨酶升高（OR 为3.8，95%CI 3.0 - 4.9）、瘙痒（OR 2.4，95%CI 1.5 - 3.9）、皮疹（OR 2.8，95%CI 2.1 - 3.8）、疲劳（OR 2.8，95%CI 2.2 - 3.7）、食欲减退（OR 2.4，95%CI 1.5 - 3.8）和垂体炎（OR 2.0，95%CI 1.2 - 3.3）更常见。腹泻（OR 8.1，95%CI 6.4 - 10.3）、结肠炎（OR 12.2，95%CI 8.7 - 17.1）、谷丙转氨酶升高（OR 5.1，95%CI 3.5 - 7.4）、谷草转氨酶升高（OR 4.2，95%CI 2.8 - 6.3）、瘙痒（OR 4.1，95%CI 2.0 - 8.4）、皮疹（OR 4.4，95%CI 2.9 - 6.8）、垂体炎（OR 12.1，95%CI 6.3 - 23.4）在CTLA - 4单克隆抗体治疗时更常见；而肺炎（OR 4.7，95%CI （2.1 - 10.3）在PD - 1单克隆抗体治疗时更常见。
结论
不同的免疫检查点抑制剂与不同的治疗相关不良事件特征相关。本系统评价中的综合数据将为临床医生提供全面信息。
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