Huang Yuchen, Ma Wananqi, Wu Dongsheng, Lyu Mengyuan, Zheng Quan, Wang Tengyong, Zhou Jian, Liu Chengwu
West China School of Medicine, Sichuan University, Chengdu, China.
Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
Transl Lung Cancer Res. 2024 Jul 30;13(7):1559-1584. doi: 10.21037/tlcr-24-299. Epub 2024 Jul 12.
Immune checkpoint inhibitors (ICIs) work by activating the immune system, a mechanism that may also cause immune-related adverse events (irAEs). This study seeks to investigate on how different irAEs impact prognosis of advanced lung cancer (LC) patients and identify useful approaches to manage irAEs.
A thorough literature search of PubMed, Embase, the Cochrane Library and manual searches up to January 2024 were undertaken. Treatment outcomes including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were obtained. Meta-analysis was conducted using R software (version 4.3.1).
There were 106 studies with 41,050 advanced or recurrent LC patients included. The occurrence of irAEs was correlated with better PFS [hazard ratio (HR) =0.54; 95% confidence interval (CI): 0.49-0.59], OS (HR =0.57; 0.51-0.63), ORR [risk ratio (RR) =2.03; 95% CI: 1.81-2.28] and DCR (RR =1.55; 95% CI: 1.40-1.72) and remained significant after adjusting programmed death-ligand 1 (PD-L1) level. IrAEs affecting skin (OS: HR =0.45; 95% CI: 0.38-0.53) and endocrine system (OS: HR =0.51; 95% CI: 0.41-0.62), of mild severity (OS: HR =0.52; 95% CI: 0.35-0.79), arising in multiple sites (OS: HR =0.47; 95% CI: 0.38-0.59), induced by monotherapy (OS: HR =0.58; 95% CI: 0.52-0.65), with a delayed onset (cutoff: 3 months; OS: HR =0.37; 95% CI: 0.19-0.71) were identified as positive prognostic markers. In contrast, though pulmonary irAEs were found to be corelated with enhanced treatment response (ORR: RR =1.75; 95% CI: 1.37-2.25), they may harm survival, especially those with grade ≥3 (OS: HR =2.40; 95% CI: 1.39-4.14). Treatment resumption tended to improve PFS but might not reduce the risk of death compared to permanent discontinuation.
IrAEs suggest better treatment outcomes generally, yet severe pneumonia could increase mortality risk. Close supervision and appropriate handling protocols are warranted to weigh treatment benefit against risk.
免疫检查点抑制剂（ICI）通过激活免疫系统发挥作用，这一机制也可能导致免疫相关不良事件（irAE）。本研究旨在探讨不同的irAE如何影响晚期肺癌（LC）患者的预后，并确定管理irAE的有效方法。
对截至2024年1月的PubMed、Embase、Cochrane图书馆进行了全面的文献检索，并进行了手工检索。获得了包括无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和疾病控制率（DCR）在内的治疗结果。使用R软件（版本4.3.1）进行荟萃分析。
纳入了106项研究，共41050例晚期或复发性LC患者。irAE的发生与更好的PFS[风险比（HR）=0.54；95%置信区间（CI）：0.49-0.59]、OS（HR =0.57；0.51-0.63）、ORR[风险比（RR）=2.03；95%CI：1.81-2.28]和DCR（RR =1.55；95%CI：1.40-1.72）相关，在调整程序性死亡配体1（PD-L1）水平后仍具有显著性。影响皮肤（OS：HR =0.45；95%CI：0.38-0.53）和内分泌系统（OS：HR =0.51；95%CI：0.41-0.62）、轻度严重程度（OS：HR =0.52；95%CI：0.35-0.79）、多部位发生（OS：HR =0.47；95%CI：0.38-0.59）、由单药治疗引起（OS：HR =0.58；95%CI：0.52-0.65）、起病延迟（临界值：3个月；OS：HR =0.37；95%CI：0.19-0.71）的irAE被确定为阳性预后标志物。相比之下，尽管发现肺部irAE与治疗反应增强相关（ORR：RR =1.75；95%CI：1.37-2.25），但它们可能损害生存，尤其是那些≥3级的患者（OS：HR =2.40；95%CI：1.39-4.14）。与永久停药相比，恢复治疗倾向于改善PFS，但可能不会降低死亡风险。
irAE通常提示更好的治疗结果，但严重肺炎可能增加死亡风险。有必要进行密切监测并制定适当的处理方案，以权衡治疗益处与风险。
