Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.352
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
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).
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.
This study focuses on the mechanisms of irAEs generation, putative relationship between dysimmune toxicity and antitumor efficacy.
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.
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.
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.
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.