Perioperative immunochemotherapy for resectable gastric or gastroesophageal junction cancer: a meta-analysis of efficacy and safety from randomized trials.

BACKGROUND: The efficacy and safety of perioperative immune checkpoint inhibitors (ICIs) combined with chemotherapy for resectable gastric/gastroesophageal junction (GEJ) cancer remain to be definitively established. This meta-analysis aimed to synthesize the latest evidence from randomized controlled trials (RCTs) on this emerging therapeutic strategy. METHODS: A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library up to June 2026 for RCTs comparing perioperative ICI plus chemotherapy with chemotherapy alone in patients with resectable gastric/GEJ cancer. Primary outcomes included pathological complete response (pCR), R0 resection rate, and survival endpoints (event-free survival [EFS] and overall survival [OS]). Safety was assessed by the incidence of adverse events. Pooled risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Seven RCTs comprising 3252 patients were included. The addition of ICIs to chemotherapy significantly improved the pCR rate compared to chemotherapy alone (RR: 2.91, 95% CI: 2.16 to 3.93, P < 0.001). The ICI-chemotherapy combination also significantly prolonged EFS (HR: 0.74, 95% CI: 0.66 to 0.83, P < 0.001) and OS (HR: 0.80, 95% CI: 0.66 to 0.95, P = 0.013). Exploratory subgroup analyses suggested numerically greater pCR benefit in patients with PD-L1 positive expression (CPS ≥1) or microsatellite instability high (MSI-H) tumors. The R0 resection rate was similar between the two groups. Moreover, the incidences of any-grade and severe adverse events showed no statistically significant difference between the two groups. CONCLUSION: This meta-analysis provides updated evidence that the addition of ICIs to perioperative chemotherapy significantly enhances pathological responses and survival outcomes in patients with resectable gastric/GEJ cancer, with a safety profile that showed no statistically significant difference in adverse events compared to chemotherapy alone. These results further reinforce the use of perioperative ICI-chemotherapy combination as a promising treatment strategy for this patient population, although confirmation in larger trials with longer follow-up is warranted.