Ramucirumab is a receptor-targeted monoclonal antibody that binds specifically to vascular endothelial growth factor (VEGF) receptor 2, blocking binding of VEGF-A, C and D. This inhibits angiogenesis thereby preventing tumours from growing the blood vessels they require to grow.
Ramucirumab is indicated for use in combination with paclitaxel or as monotherapy when treatment in combination with paclitaxel is not appropriate.
The RAINBOW study evaluated the efficacy of ramucirumab plus paclitaxel (n=330) versus placebo plus paclitaxel (n=335) in patients with locally recurrent and unresectable or metastatic gastric cancer (including GEJ adenocarcinoma) following platinum- and fluoropyrimidine-containing chemotherapy, with or without anthracycline. Ramucirumab 8mg/kg or placebo was administered on days 1 and 15 of a 28-day cycle and paclitaxel 80mg/m2 on days 1, 8 and 15.
Patients in the ramucirumab plus paclitaxel group had significantly improved overall survival compared with those in the placebo group (median 9.6 months versus 7.4 months [p=0.0169]). Progression-free survival was also significantly improved in the ramucirumab group (median 4.4 months versus 2.9 months in the placebo group, p<0.0001). A similar percentage of patients in each group discontinued treatment because of adverse events (12% in the ramucirumab group versus 11% in the placebo group).
Use of ramucirumab as monotherapy was assessed in the placebo-controlled REGARD study, which enrolled a similar population to the RAINBOW study. Patients were randomised to receive ramucirumab 8mg/kg (n=238) or placebo (n=117) every two weeks plus best supportive care.
Overall survival was significantly improved in the ramucirumab group (median 5.2 months versus 3.8 months for placebo, p=0.0473) corresponding to a 22% reduction in the risk of death for ramucirumab-treated patients. Adverse effects led to discontinuation of treatment in 11% of patients treated with ramucirumab and 6% of those who received placebo.