In the global phase III RAINBOW trial in patients with metastatic gastric cancer, the investigational monoclonal antibody ramucirumab significantly improved both progression-free and overall survival, when added to paclitaxel in second-line therapy, as reported at the 2014 Gastrointestinal Cancers Symposium.1
“The primary endpoint of improved overall survival was met,” Hansjochen Wilke, MD, of the Department of Oncology, Kliniken Essen-Mitte in Essen, Germany, reported in a press briefing. “A statistically significant and clinically meaningful overall survival benefit of more than 2 months was observed for ramucirumab plus paclitaxel vs paclitaxel alone.”
“This is one of the few trials in gastric cancer that has been significantly positive for all the efficacy parameters,” he added.
Ramucirumab is a human IgG1 monoclonal antibody that blocks vascular endothelial growth factor receptor 2 (VEGFR-2), and therefore thwarts angiogenesis.
Dr. Wilke noted that patients with disease progression after first-line treatment usually had a median survival of only about 3 months with best supportive care, and only about one-third of patients in the Western world receive second-line therapy. RAINBOW is the largest clinical trial of second-line therapy in this patient population to date.
RAINBOW Details
This randomized, double-blind, placebo-controlled study included 665 patients with metastatic gastroesophageal junction or gastric adenocarcinoma who had disease progression while on or within 4 months after a standard first-line platinum- and fluoropyrimidine-based combination chemotherapy. They were randomly assigned to receive paclitaxel alone (80 mg/ m2 on days 1, 8, 15) or with ramucirumab (8 mg/ kg IV every 2 weeks) in 4-week cycles until progression or intolerable toxicity. The primary endpoint was overall survival.
All efficacy parameters favored the ramucirumab arm. Median overall survival was 9.6 months for the combination and 7.4 months for paclitaxel alone. The hazard ratio was 0.807 (P = .0169)—a 19% reduction in risk of death with ramucirumab plus paclitaxel. Median progression-free survival was 4.4 months and 2.9 months, respectively, the hazard ratio was 0.635 (P < .0001)—a 36% reduction in risk of tumor progression or death. Median time to progression was 5.5 months and 3.0 months, respectively (P < .0001).
The objective response rate with the combination was 28%, vs 16% with paclitaxel alone (P = .0001), and the disease control rate was 80% and 64%, respectively (P < .0001).
“Disease control and response rates are important, because many of our patients are symptomatic,” Dr. Wilke noted.
Treatment-emergent adverse events of grade ≥ 3 occurred at a greater frequency in the ramucirumab plus paclitaxel arm (82% vs 63%). Grade ≥ 3 treatment-emergent adverse events occurring in more than 10% of patients and at a higher incidence in the ramucirumab plus paclitaxel arm were neutropenia, leukopenia, hypertension, and fatigue. Neutropenia grade 3 (22% vs 16%) and 4 (19% vs 3%) were reported with a higher incidence in the ramucirumab plus paclitaxel arm.
“Neutropenia was more frequently reported in the ramucirumab/paclitaxel arm, but the incidence of febrile neutropenia was comparable [3.1% vs 2.4%],” Dr. Wilke said. “Adverse events did not lead to a higher discontinuation rate, which was 11% in each arm.” ■
Disclosure: Dr. Wilke has received honoraria from Lily.
Reference
1. Wilke H, Van Cutsem E, Oh SC, et al: 2014 Gastrointestinal Cancers Symposium. Abstract LBA7. Presented January 16, 2014.
