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免疫相关不良反应:免疫检查点抑制剂疗效的有前景预测指标。

Immune-related adverse events: promising predictors for efficacy of immune checkpoint inhibitors.

机构信息

Department of Oncology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, China.

Department of Oncology, The Second Hospital of Longyan, Fujian, 364000, China.

出版信息

Cancer Immunol Immunother. 2021 Sep;70(9):2559-2576. doi: 10.1007/s00262-020-02803-5. Epub 2021 Feb 12.

Abstract

PURPOSE

This study was designed to investigate the correlation between immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) and corresponding efficacy, and to explore the potential of predicting the efficacy of ICIs via irAEs.

METHODS

Electronic databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang were applied to search for relevant studies. The primary endpoint was overall survival (OS) or progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR). Stratification analyses were conducted according to the type of irAEs and ICIs, region of studies and primary tumors. Furthermore, statistical analyses were realized by means of RevMan 5.3 software.

RESULTS

Altogether, 40 studies with 8,641 participants were enrolled, among which the incidence of irAEs ranged from 15.34 to 85.23% and the major sites reached out to skin, endocrine organ, gastrointestinal tract, liver and lung. The ORR, OS and PFS in irAE group were significantly higher than those in non-irAE group as per pooled analyses and stratification analyses. Importantly, patients with irAEs in skin, endocrine organ or gastrointestinal tract rather than in liver and lung were found to obtain survival benefits (p < 0.05).

CONCLUSION

IrAEs, especially in skin, endocrine organ or gastrointestinal tract, triggered by ICIs indicate significant survival benefits.

摘要

目的

本研究旨在探讨免疫检查点抑制剂(ICIs)相关免疫不良反应(irAEs)与相应疗效之间的相关性,并探索通过 irAEs 预测 ICI 疗效的潜力。

方法

检索 PubMed、Embase、Cochrane 图书馆、中国知网(CNKI)和万方数据库,纳入相关研究。主要终点为总生存期(OS)或无进展生存期(PFS),次要终点为客观缓解率(ORR)。根据 irAEs 类型和 ICI、研究区域和原发肿瘤进行分层分析。此外,采用 RevMan 5.3 软件进行统计分析。

结果

共纳入 40 项研究,共计 8641 名参与者,irAEs 的发生率为 15.34%至 85.23%,主要发生部位为皮肤、内分泌器官、胃肠道、肝脏和肺部。荟萃分析和分层分析显示,irAE 组的 ORR、OS 和 PFS 均显著高于非 irAE 组。重要的是,与发生在肝脏和肺部的 irAEs 相比,发生在皮肤、内分泌器官或胃肠道的 irAEs 患者具有生存获益(p<0.05)。

结论

ICIs 引发的 irAEs,特别是皮肤、内分泌器官或胃肠道的 irAEs,提示具有显著的生存获益。

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