An investigational drug improved median survival while reducing risk of disease progression or death in persons with metastatic gastric cancer participating in the phase III REGARD trial.
REGARD was designed to compare ramucirumab and best supportive care (BSC) with placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction adenocarcinoma following disease progression after first-line platinum-containing or fluoropyrimidine-containing combination therapy. Ramucirumab is a fully human immunoglobulin G1 monoclonal antibody receptor antagonist that targets vascular endothelial growth factor receptor–2 (VEGFR-2).
The study, funded by ramucirumab developer ImClone Systems (a subsidiary of Eli Lilly and Company), was conducted from October 2009 through January 2012 in 119 centers across 29 countries on six continents. After 6 months of treatment, patient survival was 40% among the 238 patients assigned to ramucirumab therapy, whereas response was notably lower among the 117 persons receiving standard treatment (below 20%, according to a statement from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, one of the study sites).
Median overall survival was 5.2 months in the ramucirumab group and 3.8 months in the placebo group. The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors, reported Josep Tabernero, MD, director of the Vall d’Hebron Institute of Oncology, and fellow REGARD investigators in The Lancet.
The ramucirumab group had a higher rate of hypertension than did the placebo group (16%, or 38 patients, compared with 8%, or nine patients). Rates of other adverse events were mostly similar between the groups, at 94% (223 patients) for ramucirumab and 88% (101 patients) for placebo. Five (2%) deaths in the ramucirumab group and two (2%) in the placebo group were considered related to the study drug.
“Ramucirumab is the first biological treatment given as a single drug that has survival benefits for persons with advance gastric or gastroesophageal junction adenocarcinoma progressing after first-line therapy,” concluded the researchers. “Our findings validate VEGFR-2 [signaling] as an important therapeutic target in advanced gastric cancer.”