Background: In recent years, immune checkpoint inhibitors (ICIs) have become a hot spot in cancer because of their remarkable survival benefits on non-small cell lung cancer (NSCLC) patients. However, the immune-related adverse events (ir-AEs) induced by ICIs have been frequently reported due to its specificity and severity. This article is to summarize and evaluate ir-AEs induced by ICIs. Hopefully it can provide guidance for advanced NSCLC patients treatment options, early recognition and management of ir-AEs.
Methods: Randomized controlled trials (RCT) which involved ICIs in the treatment of advanced NSCLC were retrieved in the Cochrane Libraby, PubMed, EMBASE and other databases. The primary outcome includes the incidence, grade and organ specificity of ir-AEs. Relative risk (RR) was used as the effect size, which was expressed as 95% confidence interval (CI). The Stata 15.0 and RevMan 5.3 software are used to conduct the meta analysis.
Results: A total of 17 RCTs were included. The ir-AEs were generally more than those in the traditional chemotherapy group. The risk and severity of ir-AEs induced by ICIs combined group were generally higher than that of ICI monotherapy, while the incidence of severe ir-AEs induced by ICIs combination therapy was similar to that of anti-cytotoxic T-lymphocyte-asscociated antigen 4 (CTLA-4) group.
Conclusions: ICIs have different toxicity profile compared with chemotherapy, and their immune-related toxicity is stronger than that of traditional chemotherapy. ICIs induced ir-AEs is organ-specific, and different ICI has specific immune-related toxicity profiles. As ICIs represent a new and distinct class of treatment for NSCLC, this article has systematically illustrated the efficacy and ir-AEs induced by ICIs, hopefully it can be useful for clinicians and patients to get a further understanding of ICIs, and facilitate early prediction, comprehensive diagnosis, and prompt management of ir-AEs by providing status reference and management suggestions, so that ICI can bring more benefit for advanced NSCLC patients.
【中文题目：ICIs治疗晚期非小细胞肺癌免疫相关不良事件的系统综述及Meta分析】 【中文摘要：背景与目的 近年来，免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）因其对非小细胞肺癌（non-small cell lung cancer, NSCLC）患者在延长生存方面显示出了显著的疗效而成为肿瘤领域的热点。但其介导的免疫相关不良事件（immune-related adverse events, ir-AEs）由于其特异性、严重性亦频发报道。本研究拟系统评价ICIs治疗晚期NSCLC患者所致ir-AEs，旨在为晚期NSCLC患者的治疗选择及ir-AEs的早期诊断和治疗提供参考。方法 检索The Cochrane Library、PubMed、EMBASE等数据库关于ICIs治疗晚期NSCLC的随机对照试验（randomized controlled trial, RCT）。主要结局指标包括ir-AEs发病数量、级别。采用相对危险度（relative risk, RR）为效应量，各效应量以95%置信区间（confidence interval, CI）表示；应用Stata 15.0/Revman 5.3软件进行meta分析。结果 本文共纳入17个RCTs。ICIs所致ir-AEs一般多于传统化疗组。在ICIs单药治疗组中，抗细胞毒性 T 淋巴细胞相关抗原 4（cytotoxic T-lymphocyte-asscociated antigen 4, CTLA-4）组所致ir-AEs的总体发病率最高；ICIs联合治疗所致各级别ir-AEs的发病率高于单药治疗组，但其所致严重ir-AEs的发病率与抗CTLA-4组相似。结论 ICIs与传统化疗毒性谱不同，其免疫相关毒性较传统化疗更强。ICIs所致ir-AEs具有器官特异性，不同类型的ICIs具有独特的免疫相关毒性谱。随着ICIs逐渐成为治疗晚期NSCLC的一种新型、有效的治疗方案，本文通过系统阐述ICIs治疗晚期NSCLC所致ir-AEs，为临床医生和患者对ICIs进一步的认识提供了帮助，并对ir-AEs的早发现、早诊断、早治疗提供数据参考及管理建议，使晚期NSCLC患者进一步从免疫疗法中获益。】 【中文关键词：免疫检查点抑制剂；肺肿瘤；免疫相关不良反应；Meta分析】.
Keywords: Immune Checkpoint Inhibitors; Immune-related adverse events; Lung neoplasms; Meta-analysis.