The predictive value of tumor mutation burden on survival of gastric cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

BACKGROUND: Tumor mutation burden (TMB) is a complement to traditional biomarkers related to the efficacy of immune checkpoint inhibitors (ICIs). The relationship between TMB and the efficacy of ICIs in gastric cancer was controversial. The systematic review and meta-analysis were conducted to investigate the predictive value of TMB on survival of gastric cancer patients treated with ICIs. METHODS: We searched the databases PubMed, Embase, and Web of Science for articles, then screened eligible articles according to inclusion criteria. The effective data were extracted to calculate the pooled effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS), then perform publication bias, sensitivity analysis, and subgroup analysis by STATA 16.0. RESULTS: The high TMB patients showed significantly longer survival than the low TMB patients (OS: HR 0.65,95% CI 0.55, 0.77, p < 0.001; PFS: HR 0.51, 95% CI 0.33, 0.77, p = 0.001). In the Asian subgroup, patients with high TMB exhibited better prognosis compared to low TMB (OS: HR 0.56, 95% CI 0.43, 0.72, p < 0.001; PFS: HR 0.45, 95% CI 0.28, 0.72, p = 0.001). In the non-Asian subgroup, the survival benefit was observed to be skewed toward patients with high TMB, but it was not statistically significant (OS:HR 0.61, 95% CI 0.32, 1.16, p = 0.133; PFS:HR 0.68, 95% CI 0.31, 1.48, p = 0.322). CONCLUSIONS: This meta-analysis demonstrated that gastric cancer patients with high TMB showed significant benefits from ICIs compared to those with low TMB patients, particularly in Asian populations.