Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.
Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.
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DOI：
10.1007/s00262-021-03128-7
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发表时间：
2022-08
影响因子：
5.8
通讯作者：
Hamnvik, Ole-Petter Riksfjord
中科院分区：
文献类型：
--
作者：
Cheung, Yee-Ming Melody;Wang, Wei;McGregor, Bradley;Hamnvik, Ole-Petter Riksfjord
关键词：
越来越多的证据表明，免疫相关不良事件 (irAE) 的发生可能是免疫检查点抑制剂 (ICI) 疗效的预测因子。这种关联是否扩展到所有 irAE 还是仅扩展到特定器官/系统内的 irAE 仍有待解决。由于免疫相关甲状腺功能障碍（甲状腺 irAE）是最常报告的 irAE 之一，本研究旨在总结现有数据并确定甲状腺 irAE 是否是 ICI 治疗期间改善癌症结果的替代标志物。截至 2021 年 7 月 1 日，PubMed、EMBASE 和 Cochrane 图书馆检索了评估 ICI 治疗期间甲状腺 irAE 发展与癌症结果之间关系的研究。感兴趣的结果指标包括总生存期 (OS) 和无进展生存期 (PFS)。还进行了基于癌症类型和永生时间偏差（ITB）调整的亚组分析。系统评价纳入了 47 项研究。 OS 荟萃分析中纳入了 21 项研究，PFS 荟萃分析中纳入了 15 项研究。 ICI 治疗期间甲状腺 irAE 的发生与 OS 和 PFS 改善相关（OS：HR 0.52，CI 0.43-0.62，p<0.001；PFS：HR 0.58，CI 0.50-0.67，p<0.001）。涉及非小细胞肺癌人群的亚组分析和考虑 ITB 的研究分别观察到相似的结果（HR 0.37，CI 0.24-0.57，p<0.001）和（HR 0.51，CI 0.39-0.69，p<0.001）。尽管存在异质性和偏差，但证据确实表明甲状腺 irAE 的发生与 ICI 的抗肿瘤作用相关，因此可以用作临床反应的替代标志物。
There is growing evidence suggesting that the occurrence of immune-related adverse events (irAEs) may be a predictor of immune checkpoint inhibitor (ICI) efficacy. Whether this association extends to all irAEs or just those within particular organs/systems is yet to be resolved. As immune-related thyroid dysfunction (thyroid irAE) is one of the most commonly reported irAEs, this study aims to summarize the available data and determine if thyroid irAE is a surrogate marker for improved cancer outcomes during ICI therapy. PubMed, EMBASE and Cochrane Library were searched up to July 1st 2021 for studies assessing the relationship between thyroid irAE development during ICI therapy and cancer outcomes. Outcome measures of interest include overall survival (OS) and progression free survival (PFS). Sub-group analyses based on cancer type and adjustment for immortal time bias (ITB) were also performed. Forty-seven studies were included in the systematic review. Twenty-one studies were included in the OS meta-analysis whilst 15 were included in the PFS meta-analysis. Development of thyroid irAE during ICI therapy was associated with improved OS and PFS (OS: HR 0.52, CI 0.43-0.62, p<0.001; PFS: HR 0.58, CI 0.50-0.67, p<0.001). Sub-group analyses involving non-small cell lung cancer populations and studies where ITB was accounted for, observed similar results (HR 0.37, CI 0.24-0.57, p<0.001) and (HR 0.51, CI 0.39-0.69, p<0.001), respectively. Despite the heterogeneity and biases identified, the evidence does suggest that the development of thyroid irAE is associated with anti-tumor effects of ICIs and therefore, can be used as a surrogate marker for clinical response.
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