New Standard of Care in Gastric Cancer

Alok A. Khorana, MD


January 31, 2014

Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-oesophageal Junction Adenocarcinoma (REGARD): An International, Randomised, Multicentre, Placebo-Controlled, Phase 3 Trial

Fuchs CS, Tomasek J, Yong CJ, et al; REGARD Trial Investigators
Lancet. 2014;383:31-39

Study Summary

The REGARD investigators evaluated the benefit of a monoclonal antibody to vascular endothelial growth factor receptor 2 in advanced gastric cancer. Patients aged 24-87 years with advanced gastric or gastroesophageal junction adenocarcinoma and disease progression after first-line platinum- or fluoropyrimidine-containing chemotherapy were randomly assigned in a 2:1 ratio to receive best supportive care plus either ramucirumab 8 mg/kg or placebo, administered intravenously once every 2 weeks.

The primary endpoint was overall survival. For 355 randomized patients, median survival was 5.2 months (interquartile range, 2.3-9.9) in the ramucirumab group and 3.8 months (interquartile range, 1.7-7.1) in the placebo group (hazard ratio [HR], 0.776; 95% confidence interval [CI], 0.603-0.998; P = .047). Adverse events were similar, with the exception of hypertension, which occurred in 16% of the study arm vs 8% of the placebo arm. Of note, there was a change in study design partway through the study: Owing to poor accrual, planned enrollment was lowered from 615 patients and 90% power to 315 patients and 80% power.


Most targeted agents in gastric cancer have failed. Trastuzumab is the notable exception, but its use is only applicable to HER2-positive patients.[1] Therefore, the study by Fuchs and colleagues represents an important advance in terms of demonstrating the efficacy of an antiangiogenic approach to gastric cancer and proving that such an approach can work even as a single agent.

Confirmation of this study is now available with the results of the RAINBOW trial, which evaluated the benefit of ramucirumab plus paclitaxel vs paclitaxel alone in a similar setting.[2]The RAINBOW trial showed significantly improved overall and progression-free survival. Median overall survival was 9.63 months for the group receiving the ramucirumab/paclitaxel combination compared with 7.36 months for the group receiving paclitaxel alone (HR, 0.807; 95% CI, 0.678-0.962; P = .0169); median progression-free survival was 4.40 months vs 2.86 months, respectively (HR, 0.635; 95% CI, 0.536-0.752; P < .0001).

On the basis of these results, ramucirumab (with or without paclitaxel) is the new standard of care in the second-line setting in patients with advanced gastric or gastroesophageal cancer.