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免疫检查点抑制剂相关肺部不良事件的比较:临床研究的回顾性分析和网状Meta分析

Comparison of immune checkpoint inhibitors related to pulmonary adverse events: a retrospective analysis of clinical studies and network meta-analysis.

作者信息

Hong Baohui, Du Bin, Chen Rong, Zheng Caiyun, Ni Ruping, Liu Maobai, Yang Jing

机构信息

Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.

Department of Pharmacy, The Second Hospital of Sanming City, Sanming, China.

出版信息

BMC Med. 2024 Feb 19;22(1):75. doi: 10.1186/s12916-024-03285-3.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have transformed tumor treatment. However, the risk of pulmonary adverse events (PAEs) associated with ICI combination therapy is still unclear. We aimed to provide a PAE overview and risk ordering of ICIs used in tumor treatment.

METHODS

We searched the databases of PubMed, PsycINFO, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, and clinical trial websites during January 2011-April 2023 to identify phase II and III randomized clinical trials (RCTs) and single-arm clinical trials wherein at least one treatment arm received ICIs (e.g., ICI monotherapy, a combination of two ICIs, or ICIs in combination with conventional cancer therapy). We reported the results of PAEs. Additionally, we compared risks of PAEs between different drug classes using a Bayesian network meta-analysis.

RESULTS

Among 143 RCTs and 24 single-arm trials, the incidence of all-grade and grade 3-4 PAEs were highest with programmed death L1 (PD-L1) plus cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and plus chemotherapy and anti-PD1 plus anti-CTLA4, the lowest with targeted therapy drug plus chemotherapy and anti-PD1 plus anti-PDL1. Anti-PD1 plus anti-CTLA4 and plus chemotherapy was the intervention with the highest risk for all-grade and 3-4 grade PAEs, and the intervention with the lowest risk was chemotherapy and anti-PD1 plus anti-PDL1. In terms of all-grade PAEs, chemotherapy was safer than ICI monotherapy. Except for the anti-PD1 plus anti-PDL1 regimen, no significant difference in the risk of grade 3-4 PAEs was detected between dual-ICIs and single-ICIs. Furthermore, the risk of PAEs associated with nivolumab, pembrolizumab, and atezolizumab may be dose dependent.

CONCLUSIONS

In the single-drug regimen, anti-PD1 caused the greatest incidence of PAEs. The risk of PAEs was higher with all single-ICIs than with chemotherapy. However, no significant difference in the risk of PAEs was detected between single-ICIs. In the combined regimen, anti-PD1 plus anti-CTLA4 and plus chemotherapy showed the greatest risk of PAEs, but there were no significant differences in risk between dual-ICIs and single-ICIs.

摘要

背景

免疫检查点抑制剂(ICIs)已经改变了肿瘤治疗方式。然而,与ICI联合治疗相关的肺部不良事件(PAEs)风险仍不明确。我们旨在对肿瘤治疗中使用的ICI进行PAE概述和风险排序。

方法

我们检索了2011年1月至2023年4月期间的PubMed、PsycINFO、Embase、Cochrane图书馆、CINAHL、Web of Science、Scopus数据库以及临床试验网站,以识别II期和III期随机临床试验(RCTs)和单臂临床试验,其中至少一个治疗组接受了ICI(例如,ICI单药治疗、两种ICI联合治疗或ICI与传统癌症治疗联合)。我们报告了PAEs的结果。此外,我们使用贝叶斯网络荟萃分析比较了不同药物类别之间PAEs的风险。

结果

在143项RCTs和24项单臂试验中,程序性死亡受体1(PD-L1)加细胞毒性T淋巴细胞相关抗原4(CTLA-4)加化疗以及抗PD1加抗CTLA4治疗时,所有级别和3-4级PAEs的发生率最高,而靶向治疗药物加化疗以及抗PD1加抗PDL1治疗时发生率最低。抗PD1加抗CTLA4加化疗是所有级别和3-4级PAEs风险最高的干预措施,而风险最低 的干预措施是化疗和抗PD1加抗PDL1。就所有级别PAEs而言,化疗比ICI单药治疗更安全。除抗PD1加抗PDL1方案外,双联ICI和单联ICI之间在3-4级PAEs风险方面未检测到显著差异。此外,与纳武单抗、帕博利珠单抗和阿特珠单抗相关的PAEs风险可能与剂量有关。

结论

在单药治疗方案中,抗PD1导致的PAEs发生率最高。所有单联ICI的PAEs风险均高于化疗。然而,单联ICI之间在PAEs风险方面未检测到显著差异。在联合治疗方案中,抗PD1加抗CTLA4加化疗显示出最高的PAEs风险,但双联ICI和单联ICI之间在风险方面无显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4b/10875746/f66b1a53eb7a/12916_2024_3285_Fig1_HTML.jpg

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