Adverse Event Risk Due to Gastric or Gastroesophageal Junction Cancer Treatment

Immune checkpoint inhibitors do not significantly increase risk for treatment-related adverse events among patients with gastric or gastroesophageal junction cancer.

Patients with advanced gastric or gastroesophageal junction cancer (AG/GEJC) receiving treatment with immune checkpoint inhibitors (ICIs) do not have a significantly increased risk for treatment-related adverse events (TRAEs). However, patients are more likely to experience TRAEs during treatment with chemotherapy or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors compared with programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors, according to findings published in Clinics and Research in Hepatology and Gastroenterology.

Researchers conducted a systematic review and meta-analysis of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from inception until May 18, 2022. Of 199 identified studies, researchers included 9, which included a total of 2918 patients with AG/GEJC.

All 9 studies assessed TRAEs after treatment with various ICI monotherapies: 5 PD-1 inhibitor trials, 2 PD-L1 inhibitor trials, 1 CTLA-4 inhibitor trial, and 1 PD-L1 and CTLA-4 inhibitor comparison and combination trial.

TRAEs occurred with a 54.5% overall incidence (95% CI, 48.7%-60.2%), while serious TRAEs grade 3 or higher occurred with an incidence of 12.8% (95% CI, 10.2%-15.7%). Rarely, ICI monotherapies caused treatment-related death at an incidence of 0.11% (95% CI, 0.00%-0.51%). The most common TRAEs included fatigue and diarrhea.

ICIs had a more manageable safety profile than chemotherapy.

When comparing the various monotherapies, patients taking CTLA-4 inhibitors demonstrated increased risk for TRAEs (any grade) than PD-1 and PD-L1 monotherapies (71.5% vs 52.3% and 50.7%, respectively). Patients treated with ICIs demonstrated lower risk for all grades of TRAEs than those treated with chemotherapies (risk ratio [RR], 0.66; 95% CI, 0.62-0.70; P <.05).

“ICIs had a more manageable safety profile than chemotherapy,” the study authors wrote. “However, CTLA-4 inhibitors were associated with higher risk of TRAEs compared with PD-1/PD-L1 inhibitors. This meta-analysis of TRAEs of ICIs can be used as a reference by clinicians and may guide clinical practice.”

Study limitations include the observational period, insufficient research, the small number of relevant studies included from the literature, difficulty performing subgroup analyses based on race and region due to heterogeneity of ethnic populations, and heterogeneity of follow-up duration in the included studies.


Yuan H, Duan DD, Zhang YJ. Comprehensive analysis of treatment-related adverse events of immunotherapy in advanced gastric or gastroesophageal junction cancer: A meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol. 2022;46(10):102031. doi:10.1016/j.clinre.2022.102031