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
ARTICLE HIGHLIGHTS
Research background

In recent years, there has been a steep rise in the development and implementation of anti-cancer immunotherapies. Although there has been a large amount of research focusing on adverse events associated with immune checkpoint inhibitors (ICIs), few studies have focused specifically on advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC).

Research motivation

By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (irAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumor response. To help clinicians effectively identify and manage irAEs as well as strike a balance are critical.

Research objectives

This study focuses on the mechanisms of irAEs generation, putative relationship between dysimmune toxicity and antitumor efficacy.

Research methods

In the study, we systematically evaluated the incidence of global irAEs and organ-specific irAEs and proposed a random-effect model and subgroup analysis based on different targets, tumor types, drug types, organ specificity, and irAE grade to reduce variance and bias.

Research results

It was found that the overall incidence of irAEs was 16% (95%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. 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.

Research conclusions

This systematic review shows that there is an increasing number of irAEs associated with ICIs that are being reported in patients with GC or GEJC. This is particularly severe for 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.

Research perspectives

In the study, we systematically evaluated the incidence of global irAEs and organ-specific irAEs and proposed a random-effect model and subgroup analysis based on different targets, tumor types, drug types, organ specificity, and irAE grade to reduce variance and bias. Another strength of our study is that both case reports and case series were included, as well as a comprehensive evaluation of the occurrence, treatment, and prognosis of irAEs. The study would be of great interest to a broad range of readers including oncologists, clinical researchers, patients, and other researchers in related fields.