Meta-Analysis
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World J Gastrointest Oncol. Feb 15, 2023; 15(2): 352-367
Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.352
Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer: A meta-analysis
Wen-Guang Pei, Wen-Zheng Chen, Yu-Kang Wu, Sheng-Xing Tan, Zhi-Gang Jie
Wen-Guang Pei, Wen-Zheng Chen, Yu-Kang Wu, Sheng-Xing Tan, Zhi-Gang Jie, Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Pei WG, Jie ZG, Chen WZ, Tan SX, Wu YK contributed to the conception and design; Pei WG, Jie ZG, Chen WZ, Tan SX, Wu YK contributed to the data collection and extraction, statistical data analysis and software utilization; Pei WG, Chen WZ, Wu YK was involved in methodology, data curation and formal analysis; Pei WG, Jie ZG contributed to the manuscript drafting; Pei WG, Jie ZG, Chen WZ, Tan SX, Wu YK contributed to the manuscript revision, and approval of the final manuscript.
Supported by The National Natural Science Foundation of China, No. 81960503.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Gang Jie, MMed, Chief Doctor, Professor, Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanchang University, No. 17 Yongwai Main Street, Donghu District, Nanchang 330006, Jiangxi Province, China. jiezg123@126.com
Received: October 10, 2022
Peer-review started: October 10, 2022
First decision: October 20, 2022
Revised: October 23, 2022
Accepted: November 28, 2022
Article in press: November 28, 2022
Published online: February 15, 2023
Processing time: 127 Days and 9.1 Hours
Abstract
BACKGROUND

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.

AIM

To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Immune checkpoint inhibitors; Advanced gastric and gastroesophageal junction cancer; Systematic review; Meta-analysis.

Core Tip: This systematic review shows that there is an increasing number of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors that are being reported in patients with gastric cancer or gastroesophageal junction cancer. This is particularly severe organ-specific irAEs and death because of irAEs, which poses significant challenges for clinical oncologists. Therefore, to help clinicians effectively identify and manage irAEs as well as strike a balance, a comprehensive understanding, systematic prediction, and appropriate management of the adverse events are critical.