Immunotherapy Combined with Chemotherapy in the First-Line Treatment of Advanced Gastric Cancer: Systematic Review and Bayesian Network Meta-Analysis Based on Specific PD-L1 CPS

Objective: To compare the efficacy and safety of immunotherapy combined with chemotherapy as the first-line treatment for advanced gastric cancer. Data Sources: Phase III randomised controlled trials were searched from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials databases, and several international conference databases, from inception to 15 November 2024. Results: A total of eight eligible trials involved 7898 patients and eight treatments. The network meta-analysis showed that cadonilimab plus chemotherapy was the most superior treatment in improving overall survival (versus conventional chemotherapy, hazard ratio 0.62, 95% credible interval 0.50 to 0.78) and progression-free survival (0.53, 0.43 to 0.65), and consistency of results were observed in specific PD-L1 combined positive score groups. All immune checkpoint inhibitors combined with chemotherapy improved patient prognosis, but nivolumab plus chemotherapy may lead to an increase in grade 3 or higher adverse events (odds ratio 1.68, 95% credible interval 1.04 to 2.54), and the toxicity of cadonilimab plus chemotherapy was more likely to force patients to discontinue treatment. Conclusions: These results showed that cadonilimab plus chemotherapy had the best overall survival and progression-free survival benefits for advanced gastric cancer patients with HER-2 negative, and was preferentially recommended to patients with positive PD-L1 CPS.