Comparative efficacy and safety of distinct PD-1 antibodies in unresectable advanced or recurrent gastric and gastroesophageal junction cancer: a network meta-analysis of randomized controlled trials

Unresectable advanced or recurrent gastric and gastroesophageal junction (GC/GEJ) cancers carry poor prognoses, and several programmed death-1 (PD-1) inhibitors have shown clinical activity. However, no head-to-head trial has compared their relative efficacy and safety. This network meta-analysis aimed to evaluate and rank PD-1–based regimens in this setting. A systematic review of PubMed, Embase, CENTRAL, Web of Science, and Google Scholar through August 10, 2025, identified randomized controlled trials enrolling adults with unresectable advanced or recurrent GC/GEJ cancer. Primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and grade ≥ 3 TRAEs. A Bayesian random-effects network meta-analysis generated mean differences (MDs) or odds ratios (ORs) with 95% confidence intervals (CIs) and calculated surface under the cumulative ranking curve (SUCRA) values. Nineteen trials (n = 9,460) were included. Nivolumab monotherapy ranked first for OS (SUCRA 98.3%) and PFS (97.6%), and improved OS versus control (HR 0.59, 95% CI 0.50–0.69). Sintilimab plus chemotherapy ranked highly for OS and PFS (SUCRA 53.9% and 70.9%) and reduced PFS risk versus pembrolizumab monotherapy (HR 0.53, 95% CI 0.35–0.82). Nivolumab plus chemotherapy also improved OS versus control (HR 0.79, 95% CI 0.68–0.92) and PFS versus pembrolizumab monotherapy (HR 0.55, 95% CI 0.42–0.72). Nivolumab monotherapy yielded the highest ORR and DCR (SUCRA 99.9% and 95.2%) but the lowest safety ranking for grade ≥ 3 TRAEs (SUCRA 7.1%). Pembrolizumab monotherapy showed the most favorable safety (SUCRA 100% for grade ≥ 3 TRAEs) but the lowest efficacy across PFS, ORR, and DCR. Across agents, PD-1 inhibitor–chemotherapy combinations reduced progression or death versus control without increasing severe toxicity. Chemoimmunotherapy should be prioritized as first-line therapy for unresectable advanced or recurrent GC/GEJ cancer, with nivolumab-based combinations offering the most favorable efficacy-safety balance. Nivolumab monotherapy provides the strongest tumor response and survival ranking but requires vigilant toxicity management. These comparative rankings can inform individualized regimen selection.