Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 ( VEGFR-2 )-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer.
A study has assessed whether Ramucirumab ( Cyramza ), a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer.
Researchers did an international, randomised, double-blind, placebo-controlled, phase 3 trial in the period 2009-2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa.
Patients aged 24-87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line Platinum-containing or fluoropyrimidine-containing chemotherapy were randomly assigned ( 2:1 ), via a central interactive voice-response system, to receive best supportive care plus either Ramucirumab 8 mg/kg or placebo, intravenously once every 2 weeks.
The primary endpoint was overall survival. Analysis was by intention to treat.
355 patients were assigned to receive Ramucirumab ( n=238 ) or placebo ( n=117 ).
Median overall survival was 5.2 months in patients in the Ramucirumab group and 3.8 months in those in the placebo group ( hazard ratio, HR=0.776; p=0.047 ).
The survival benefit with Ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR=0.774; p=0.042 ).
Rates of hypertension were higher in the Ramucirumab group than in the placebo group ( 38 [ 16% ] vs 9 [ 8% ] ), whereas rates of other adverse events were mostly similar between groups ( 223 [ 94% ] vs 101 [ 88% ]). Five ( 2% ) deaths in the Ramucirumab group and two ( 2% ) in the placebo group were considered to be related to study drug.
Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy.
These findings validate VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer. ( Xagena )
Fuchs CS et al, The Lancet 2014; 383: 31-39