No benefit from ramucirumab in first-line chemotherapy?

Ramucirumab is a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting human vascular endothelial growth factor receptor-2 (VEGFR-2). It prevents the binding of VEGFR-2 with its ligands including VEGF-A, VEGF-C, and VEGF-D. Thus, receptor activation and vascular endothelial growth factor (VEGF) signal pathways are inhibited, leading to the reduction of tumor neovascularization and growth. Ramucirumab is the only biologic agent targeting angiogenesis that has shown a survival benefit in gastric or gastroesophageal junction adenocarcinoma in phase III trials. Two phase III trials, REGARD and RAINBOW (1,2), demonstrated an improvement in overall survival (OS). The REGARD trial was a phase III, international, randomized, double-blind, placebo-controlled trial (1). Patients were eligible who had metastatic gastric or gastroesophageal junction adenocarcinoma after the failure of first-line platinum or fluoropyrimidine-containing combination therapy; 355 patients were assigned in a 2:1 ratio, to receive best supportive care plus either ramucirumab at 8 mg/kg (n=238) or placebo (n=117) once every 2 weeks.