BACKGROUND: Perioperative systemic therapy is the standard of care for resectable locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. The emergence of multiple chemoimmunotherapy regimens warrants updated comparative evaluation. METHODS: A systematic review identified randomized controlled trials evaluating systemic therapy strategies for resectable locally advanced G/GEJ adenocarcinoma. Chemoradiotherapy-based approaches were not included. Overall survival (OS), disease-free survival (DFS), grade 3-4 adverse events, treatment-related discontinuation, and treatment-related deaths were analyzed. A Bayesian random-effects network meta-analysis was conducted, with treatment rankings based on surface under the cumulative ranking curve (SUCRA). RESULTS: Across 30 trials (11,547 patients), sixteen strategies were compared. Perioperative taxane-based triplet chemotherapy (P-Trp-Tax) plus an immune checkpoint inhibitor (ICI) ranked highest for OS (SUCRA = 0.952) and DFS (SUCRA = 0.959). P-Trp-Tax + ICI showed a numerically favorable trend compared with P-Trp-Tax for OS (HR 0.79; 95% CrI, 0.59-1.05), although the estimate was imprecise. A more consistent benefit was observed for DFS (HR 0.72; 95% CrI, 0.56-0.93). Comparisons versus P-Dbl + ICI were imprecise (OS HR 0.76; 95% CrI, 0.45-1.26; DFS HR 0.74; 95% CrI, 0.46-1.19). Toxicity profiles were consistent with known patterns, without increased high-grade adverse events with ICIs, with estimates limited by heterogeneity and sparse data. CONCLUSIONS: P-Trp-Tax + ICI had the highest probability of being among the most effective strategies in this analysis. These findings suggest a potential benefit of treatment intensification, but should be interpreted with caution given reliance on indirect comparisons, limited direct evidence for key regimens, and wide credible intervals for several estimates.
Nohmi et al. (2026) studied this question.