Efficacy and Safety of Zolbetuximab in Gastric Cancer

Abstract

Gastric cancer remains a major global health concern with high incidence and mortality rates, particularly in East Asia. Patients often have poor outcomes due to limited treatment efficacy. Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2)-overexpressed in 50% to 80% of gastric cancers-demonstrates promise by initiating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in CLDN18.2-positive cells. In clinical trials, zolbetuximab with chemotherapy improved progression-free survival (PFS) and overall survival (OS). The FAST trial showed a median OS increase from 8.4 months to 13.2 months (HR, 0.72; P < .01). The SPOTLIGHT trial found PFS extended to 11.0 months vs. 8.9 months (HR, 0.73; P = .0024) with OS reaching 18.2 months in the zolbetuximab arm. The GLOW trial also confirmed efficacy, with median OS improving from 12.16 months to 14.39 months (HR, 0.771; P = .0118). Zolbetuximab's targeted action, combined with manageable adverse effects, positions it as a promising therapy for advanced gastric cancer.