Association of Immune Related Adverse Events With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Cancers: A Systemic Review and Meta-analysis.
Association of Immune Related Adverse Events With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Cancers: A Systemic Review and Meta-analysis.
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DOI：
10.3389/fonc.2021.633032
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Fan Y;Xie W;Huang H;Wang Y;Li G;Geng Y;Hao Y;Zhang Z
免疫检查点抑制剂（ICI）为癌症患者带来了令人印象深刻的益处，但通常伴随着免疫相关不良事件（irAE）。我们旨在研究接受ICI治疗的癌症患者中irAE与疗效和总生存期的相关性，并通过分层亚组进一步量化相关性。系统检索了PubMed、EMBASE和科克伦图书馆从数据库建立到2019年8月29日的数据。纳入了报告接受获批ICI治疗的癌症患者的客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）与irAE相关性的文章。计算ORR的校正比值比（OR）和95%置信区间（CI），PFS和OS使用风险比（HR）。共纳入52篇文章，包括9，156例患者。汇总数据显示，与未发生irAE的患者相比，发生irAE的患者实现客观肿瘤缓解的概率在统计学上显著更高（OR 3.91，95% CI 3.05-5.02）。在总体荟萃分析中，发生irAE的患者的PFS（HR 0.54; 95% CI 0.46-0.62）和OS（HR 0.51; 95% CI 0.41-0.59）延长。更具体地说，某些癌症类型（NSCLC和黑色素瘤）和器官（皮肤和内分泌）中的irAE与更好的临床结局密切相关，而这种相关性需要进一步验证其他肿瘤。高级别毒性（G3-5）与显著有利的PFS或OS无关。此外，在接受PD-（L）1阻滞剂的患者中，irAE与临床获益之间的相关性似乎比CTLA-4阻滞剂更明确。地标分析的汇总数据显示了一致的结果。irAE的发生预测了接受ICI治疗的总体癌症患者的肿瘤缓解改善和生存期延长。值得注意的是，这种关联在某些癌症类型（NSCLC和黑色素瘤）和器官特异性irAE（皮肤和内分泌）中保持稳健。
Immune checkpoint inhibitors (ICIs) have brought impressive benefits to cancer patients, however often accompanied with immune-related adverse events (irAEs). We aimed to investigate the association of irAEs with efficacy and overall survival in cancer patients treated by ICIs, and further quantify the association by stratifying subgroups. PubMed, EMBASE and Cochrane library from database inception to 29 August 2019 were systematically searched. Articles reporting association of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) with irAEs in cancer patients treated with approved ICIs were included. Adjusted odds ratios (OR) with 95% confidential intervals (CIs) were calculated for ORR, and hazard ratios (HR) were used for PFS and OS. A total of 52 articles comprising 9,156 patients were included. Pooled data demonstrated a statistically significant greater probability of achieving objective tumor response for patients with irAEs compared to those without (OR 3.91, 95% CI 3.05–5.02). In overall meta-analysis, patients who developed irAEs presented a prolonged PFS (HR 0.54; 95% CI 0.46–0.62) and OS (HR 0.51; 95% CI 0.41–0.59). More specifically, irAEs in certain cancer types (NSCLC and melanoma) and organs (skin and endocrine) were robustly associated with better clinical outcomes, while this association needs further verification regarding other tumors. High grade toxicities (G3–5) were not associated with a significantly favorable PFS or OS. Additionally, the association between irAEs and clinical benefit seemed to be more definite in patients receiving PD-(L)1 blockade than CTLA-4 blockade. Pooled data from landmark analyses displayed consistent results. The occurrence of irAEs predicted improved tumor response and better survival in overall cancer patients treated with ICIs. Notably, the association stayed robust in certain cancer types (NSCLC and melanoma) and organ-specific irAEs (skin and endocrine).
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影响因子：
3.1
作者：
Bjornhart, Birgitte;Hansen, Karin H.;Schytte, Tine
通讯作者：
Schytte, Tine
影响因子：
5.3
作者：
Fujimoto, Daichi;Yoshioka, Hiroshige;Hirai, Toyohiro
通讯作者：
Hirai, Toyohiro
影响因子：
10.9
作者：
Hua, Camille;Boussemart, Lise;Robert, Caroline
通讯作者：
Robert, Caroline
影响因子：
4.7
作者：
Hommes JW;Verheijden RJ;Suijkerbuijk KPM;Hamann D
通讯作者：
Hamann D
影响因子：
6.2
作者：
Faje, Alexander T.;Lawrence, Donald;Sullivan, Ryan J.
通讯作者：
Sullivan, Ryan J.