Efficacy and Safety of Pembrolizumab in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis

This meta-analysis integrates data from 7 randomized controlled trials comprising 4,560 patients with advanced gastric cancer to evaluate the efficacy and safety of pembrolizumab as monotherapy or in combination with chemotherapy. Compared to control treatments, pembrolizumab significantly improved overall survival and objective response rate, though no significant difference was observed in progression-free survival. While the risk of immune-related adverse events and severe treatment-related adverse events increased with pembrolizumab, the incidence of all-grade adverse events was not significantly different. Importantly, pembrolizumab was not associated with an increased risk of treatment-related death (OR = 0.99, 95% CI 0.59-1.65), indicating that the risk of fatal adverse events is comparable to that of chemotherapy alone. This finding helps address a common clinical concern regarding the safety profile of immunotherapy. Subgroup analyses revealed that patients with PD-L1 combined positive score of 10 or higher derived the greatest benefit in objective response rate and progression-free survival. Combination therapy demonstrated superior efficacy over monotherapy across all survival outcomes but was associated with higher immune-related toxicity. Based on these findings, pembrolizumab in combination with chemotherapy is recommended as first-line treatment for patients with good performance status and PD-L1 combined positive score of 10 or higher. For elderly patients or those with reduced performance status, monotherapy may offer a favorable balance between efficacy and safety. Routine PD-L1 testing and proactive adverse event management are essential for optimizing treatment outcomes.