免疫相关的不良事件（irAEs）在免疫检查点抑制剂（ICI）治疗过程中经常发生，并与长期结局相关。 irAE的发生是否是ICI疗效的有效代理尚未知。我们通过系统搜索鉴定了报道实验性ICI治疗固体肿瘤的随机试验结果的文章。对照组可以是安慰剂、细胞毒性/靶向治疗或ICI治疗。我们提取了每组总生存期（OS）的风险比、每组OS事件的数量和百分比以及每组整体和特定1-2级和3-4级irAE的数量和百分比。我们估计了潜在代理结果的治疗效果，通过实验组与对照组之间irAE率的比值。统计分析涉及对irAE率治疗效果和OS治疗效果之间的对数比例进行加权线性回归。共纳入了62个随机试验，涉及79个对比和42,247名患者。分析发现在整体级别1-2级或3-4级irAE率或特定（皮肤，胃肠，内分泌）irAE率的治疗效果之间没有显着关联。在非小细胞肺癌（NSCLC）试验子集中，我们观察到在选择程序性死亡配体1表达的患者的研究中，整体级别1-2级irAE的治疗效果和OS治疗效果之间存在负相关关系（R2 = 0.55；95％置信区间0.20-0.95; R = -0.69）。在黑色素瘤试验子集中，显示出在没有基于ICI的对照组试验中治疗效果在胃肠道3-4级irAE方面的负相关关系（R2 = 0.77；95％置信区间0.24-0.99; R = -0.89) 和OS治疗效果之间。在多种癌症类型中，ICI治疗对整体或特定irAE率的影响与治疗对OS的影响之间存在弱相关性。版权所有© 2023年作者。由Elsevier Ltd.出版。保留所有权利。

Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy.We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS.Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R2 = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R2 = 0.77; 95% confidence interval 0.24-0.99; R = -0.89).We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.