Unlocking the potential of zolbetuximab in CLDN18.2-positive gastric cancer: A comprehensive systematic review of clinical efficacy and safety.

e16069 Background: Zolbetuximab, a monoclonal antibody targeting Claudin 18.2 (CLDN18.2), has demonstrated efficacy in treating CLDN18.2-positive gastric cancer by inducing cytotoxicity in cancer cells. This review evaluates its clinical impact on survival outcomes and safety profile. Methods: A systematic search of Medline, PubMed, Google Scholar, and PsycINFO up to January 20, 2025, identified 324 studies, of which 20 met inclusion criteria. Eligible studies reported progression-free survival (PFS) and overall survival (OS). Data were extracted using Rayyan software, and statistical analyses, including random-effects models, were performed using SPSS. Confounding factors were addressed through multivariate regression, and the study protocol was independently reviewed. Results: In 20 studies involving 3,217 patients, Zolbetuximab combined with chemotherapy improved PFS by 6.8 months (95% CI: 5.7–7.9) and reduced the risk of death (HR: 0.68, 95% CI: 0.56–0.81). Notably, the FAST trial reported a median OS increase from 8.4 to 13.2 months (HR: 0.72; P < .01), and the SPOTLIGHT trial found PFS extended to 11.0 months versus 8.9 months (HR: 0.73; P = .0024), with OS reaching 18.2 months in the Zolbetuximab arm. Common adverse events included nausea (32%), vomiting (24%), and fatigue (18%), with dose-limiting toxicities in 8%. The recommended dose of 800 mg/m² biweekly demonstrated sustained target engagement, with a median half-life of 12 days. Conclusions: Zolbetuximab significantly improves survival outcomes in CLDN18.2-positive gastric cancer with manageable toxicity. These findings support its use with chemotherapy and highlight the need for further trials to optimize dosing and explore novel combinations.