Eli Lilly and Co. announced that results from the Phase 3 REGARD trial of ramucirumab (IMC-1121B) as a single agent in patients with advanced gastric cancer who have had disease progression after initial chemotherapy were published today in The Lancet. REGARD is the first Phase 3 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 3 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 achieved a median overall survival of 5.2 months compared to 3.8 months for patients on the placebo arm, representing a 37 percent increase. The overall survival hazard ratio was 0.776 (95 percent CI), which corresponds to a 22 percent 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 (95 percent CI).
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 percent on ramucirumab vs 3 percent on placebo) and abdominal pain (6 percent vs 3 percent). 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 percent vs 2.6 percent), arterial thromboembolic events (1 percent vs 0 percent) and proteinuria (0.4 percent vs 0 percent). Additional adverse events ( > 5 percent 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 percent vs 0.9 percent) and hypokalemia (2.1 percent vs 0.9 percent), and those with a higher rate (any grade) on the ramucirumab arm included headache (9.3 percent vs 3.5 percent) and diarrhea (14.4 percent vs 8.7 percent). Five (2 percent) deaths in the ramucirumab group and two (2 percent) deaths in the placebo group (2:1 randomization) were reported by the investigator to be related to treatment.
“We are pleased with this data of ramucirumab as a single agent in advanced gastric cancer, a devastating disease where the prognosis for patients is poor. There are no agents specifically approved in the U.S. or EU for advanced gastric cancer patients in this setting,” said Richard Gaynor, vice president, product development and medical affairs for Lilly Oncology. “Gastric cancer is the fourth most common cancer in the world and the second-leading cause of cancer-related death — this is a major global health issue.”
“What we found is that the patients who received ramucirumab had a significant improvement in their survival as well as reducing the rate of cancer progression. The side effects associated with ramucirumab, except for hypertension, were mostly similar to what patients receiving placebo experienced,” said Charles S. Fuchs, director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute. “The results are very encouraging for patients with stomach cancer.”
REGARD is one of two ramucirumab Phase 3 studies in gastric cancer. RAINBOW, a global Phase 3 study of ramucirumab in combination with paclitaxel in patients with advanced gastric cancer, met its primary endpoint of improved overall survival and a secondary endpoint of improved progression-free survival, Lilly announced last week.
The REGARD single-agent ramucirumab data are the basis for current U.S. and EU regulatory submissions. The RAINBOW combination-therapy ramucirumab data will be the basis for separate regulatory applications.
Date: October 3, 2013
Source: Eli Lilly and Co.