Table_2_Immune-related adverse events and their effects on survival outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.doc

BackgroundThe use of immune checkpoint inhibitors (ICIs) has become the standard of care for non-small cell lung cancer. The purpose of this study was to systematically review the literature to determine whether the occurrence of immune-related adverse events (irAEs) following the use of ICIs predicts different clinical outcomes in non-small cell lung cancer (NSCLC).
MethodsRelevant studies from the time of database creation to July 20, 2023, were systematically searched to explore the differences in clinical outcomes in patients with advanced NSCLC with or without irAEs. The outcome indicators included the occurrence of irAEs, progression-free survival (PFS), and overall survival (OS).
Results25 studies met the inclusion criteria. Of these studies, 22 reported the effect on OS, and 19 reported the effect on PFS. The results showed that for patients with NSCLC, the occurrence of irAEs after receiving immunotherapy showed a statistically significant benefit over the absence of irAEs for OS (HR=0.55,95% CI=0.46–0.65) and PFS (HR=0.55 95% CI=0.48–0.64), but severe irAEs (grades 3–5) were associated with worse OS (HR=1.05, 95% CI=0.87–1.27). Compared with gastrointestinal, lung, and hepatitis, irAEs of the skin and endocrine system tend to predict better OS and PFS.
ConclusionThe occurrence of irAEs, especially mild and early irAEs, indicates better OS and PFS in patients with NSCLC treated with ICIs, irrespective of patient characteristics, type of ICIs, and irAEs. However, Grade 3 or higher toxicities resulted in worse OS.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023409444.

背景：免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）已成为非小细胞肺癌（non-small cell lung cancer, NSCLC）的标准治疗方案。本研究旨在通过系统综述文献，明确免疫检查点抑制剂使用后发生的免疫相关不良事件（immune-related adverse events, irAEs）是否可预测非小细胞肺癌患者的不同临床结局。

方法：本研究系统检索了从数据库建库至2023年7月20日的相关研究，以探讨伴或不伴免疫相关不良事件的晚期非小细胞肺癌患者的临床结局差异。结局指标包括免疫相关不良事件的发生情况、无进展生存期（progression-free survival, PFS）以及总生存期（overall survival, OS）。

结果：共有25项研究符合纳入标准。其中22项研究报告了对总生存期的影响，19项研究报告了对无进展生存期的影响。结果显示，对于非小细胞肺癌患者，接受免疫治疗后发生免疫相关不良事件者，其总生存期（HR=0.55，95%置信区间CI=0.46–0.65）与无进展生存期（HR=0.55，95%置信区间CI=0.48–0.64）均显著优于未发生免疫相关不良事件者，但重度免疫相关不良事件（3~5级）与更差的总生存期相关（HR=1.05，95%置信区间CI=0.87–1.27）。相较于胃肠道、肺部与肝脏相关的免疫相关不良事件，皮肤及内分泌系统的免疫相关不良事件往往预示着更好的总生存期与无进展生存期。

结论：免疫相关不良事件的发生，尤其是轻度与早期免疫相关不良事件，提示接受免疫检查点抑制剂治疗的非小细胞肺癌患者拥有更好的总生存期与无进展生存期，这一结果不受患者特征、免疫检查点抑制剂类型以及免疫相关不良事件类型的影响。但3级及以上的毒性反应则与更差的总生存期相关。

系统综述注册信息：https://www.crd.york.ac.uk/prospero/，标识符CRD42023409444。