The results from the Phase III REGARD trial of Ramucirumab as a single agent in patients with advanced gastric cancer who have had disease progression after initial chemotherapy were published in The Lancet.
REGARD is the first phase III study with either a single-agent biologic or an anti-angiogenic therapy to show improved overall survival and progression-free survival in advanced gastric cancer patients.
REGARD is a global, randomized, double-blind phase III study of Ramucirumab and best supportive care compared to placebo and best supportive care as treatment in patients with advanced gastric cancer following progression after initial chemotherapy. Patients ( n=355 ) were randomly assigned in a 2:1 ratio, to receive best supportive care plus either Ramucirumab 8 mg/kg or placebo, intravenously once every two weeks. Median duration of treatment was eight weeks in the Ramucirumab group and six weeks in the placebo group.
Patients treated with single-agent Ramucirumab ( n=238 ) achieved a median overall survival of 5.2 months compared to 3.8 months for patients on the placebo arm ( n=117 ), representing a 37% increase. The overall survival hazard ratio was 0.776 ( p=0.0473 ), which corresponds to a 22% reduction in risk of death. Patients on the Ramucirumab arm achieved a median progression-free survival of 2.1 months compared to 1.3 months for those on the placebo arm. The progression-free survival hazard ratio was 0.483 ( p less than 0.0001 ).
In the REGARD analysis reported in The Lancet, the following adverse events occurred at a higher rate ( for grade 3 or higher ) on the Ramucirumab arm: hypertension ( 8% on Ramucirumab vs 3% on placebo ) and abdominal pain ( 6% vs 3% ). No grade 4 hypertension was observed on the Ramucirumab arm.
Adverse events of special interest occurring on the Ramucirumab arm at a higher rate for grade 3 or higher were bleeding or hemorrhage ( 3.4% vs 2.6% ), arterial thromboembolic events ( 1% vs 0% ) and proteinuria ( 0.4% vs 0% ).
Additional adverse events ( greater than 5% any grade ) that have been previously reported for REGARD and occurring at a higher rate ( for grade 3 or higher ) on the Ramucirumab arm included hyponatremia ( 3.4% vs 0.9% ) and hypokalemia ( 2.1% vs 0.9% ), and those with a higher rate ( any grade ) on the Ramucirumab arm included headache ( 9.3% vs 3.5% ) and diarrhea ( 14.4% vs 8.7% ). Five ( 2% ) deaths in the Ramucirumab group and two ( 2% ) deaths in the placebo group ( 2:1 randomization ) were reported by the investigator to be related to treatment. ( Xagena )
Source: Lilly, 2013