Pei Wen-Guang, Chen Wen-Zheng, Wu Yu-Kang, Tan Sheng-Xing, Jie Zhi-Gang
Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
World J Gastrointest Oncol. 2023 Feb 15;15(2):352-367. doi: 10.4251/wjgo.v15.i2.352.
Immune checkpoint inhibitors (ICIs) have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer. However, the inhibitors also cause immune-related adverse events (irAEs). The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs.
To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.
This systematic review was registered with PROSPERO (Reg. number: CRD42020152291). Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs. A systematic literature search was conducted using the PubMed, EMBASE, and Cochrane Library databases. Meta-analysis was carried out using the single sample rate method. Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software.
The patients enrolled in the present study included 14 patients from 14 case reports, 326 patients from 6 case series, and 1249 patients from 8 clinical trials. It was found that the overall incidence of irAEs was 16% [95% confidence interval (CI): 11-20] for all grades and 3% (95%CI: 2-4) for the severe grade. It was evident that the incidence of irAEs varied with the type of inhibitor and organs. A comparative study of the anti-programmed cell death receptor-1 (PD-1) and anti-programmed death receptor-ligand 1 (PD-L1) treatments showed that the anti-PD-1 group had a higher overall incidence of irAEs (20%) as compared with that of the anti-PD-L1 group (13%). Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs (7.4%), including hypothyroidism, hyperthyroidism, thyroiditis, diabetes, and adrenal insufficiency, followed by gastroenterology (2.2%), pulmonology (1.8%), neurology (1.4%), dermatology (1.4%), hematology (0.8%), and hepatology (0.7%). In clinical trials, it was found that the incidence of death related to irAEs was 1% (95%CI: 0-2.0), whereby colitis and interstitial lung diseases were the leading causes of death.
It was evident that the incidence and nature of irAEs are both organ- and inhibitor-specific. The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs. Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.
免疫检查点抑制剂（ICI）在晚期胃癌和胃食管交界癌的治疗及临床管理中已显示出有前景的疗效。然而，这些抑制剂也会引发免疫相关不良事件（irAE）。当前的系统评价和荟萃分析研究旨在调查ICI所致irAE的发生率及性质。
调查晚期胃癌和胃食管交界癌中irAE的发生率及性质。
本系统评价在国际前瞻性系统评价注册库（PROSPERO）进行了注册（注册号：CRD42020152291）。本研究纳入的数据收集自诊断为晚期胃癌或胃食管交界癌并接受ICI治疗的患者。使用PubMed、EMBASE和Cochrane图书馆数据库进行系统文献检索。采用单样本率法进行荟萃分析。使用Stata/SE和Review Manager软件进行数据的综合与分析。
本研究纳入的患者包括来自14篇病例报告的14例患者、来自6个病例系列的326例患者以及来自8项临床试验的1249例患者。结果发现，所有级别的irAE总体发生率为16%[95%置信区间（CI）：11 - 20]，严重级别的发生率为3%（95%CI：2 - 4）。显然，irAE的发生率因抑制剂类型和器官而异。一项抗程序性细胞死亡受体1（PD - 1）和抗程序性死亡受体配体1（PD - L1）治疗的对比研究表明，抗PD - 1组的irAE总体发生率（20%）高于抗PD - L1组（13%）。本研究结果显示，内分泌系统发生器官特异性irAE的发生率最高（7.4%），包括甲状腺功能减退、甲状腺功能亢进、甲状腺炎、糖尿病和肾上腺功能不全，其次是胃肠病学（2.2%）、肺病学（1.8%）、神经病学（1.4%）、皮肤病学（1.4%）、血液学（0.8%）和肝病学（0.7%）。在临床试验中，发现与irAE相关的死亡发生率为1%（95%CI：0 - 2.0），其中结肠炎和间质性肺病是主要死因。
显然，irAE的发生率和性质均具有器官和抑制剂特异性。抗PD - 1组所有级别的irAE包括严重级别的irAE发生率最高。对irAE进行早期识别和管理可使临床肿瘤学家有效权衡利弊，从而实现平衡。
