Charles S. Fuchs
The addition of ramucirumab to first-line chemotherapy conferred a 25% reduction in risk for disease progression or death among treatment-naive patients with metastatic gastric or gastroesophageal junction adenocarcinoma, according to results of a randomized phase 3 study scheduled for presentation at the Gastrointestinal Cancers Symposium.
However, ramucirumab (Cyramza, Eli Lilly) did not improve OS.
Ramucirumab is a VEGFR-2 IgG1 human monoclonal antibody and is the only biologic with proven efficacy as both a single agent and in combination with paclitaxel in the second-line treatment of gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.
During RAINFALL — a global, double-blind, placebo-controlled randomized clinical trial — researchers addressed the hypothesis that adding ramucirumab to first-line cisplatin plus capecitabine or 5-FU would produce significant clinical benefit.
Charles S. Fuchs, MD, MPH, director of Yale Cancer Center, and colleagues randomly assigned 645 patients with metastatic G-GEJ adenocarcinoma who were eligible for first-line chemotherapy and had an ECOG performance status of 0 to 1 to ramucirumab (8 mg/kg via IV on days 1 and 8; n = 326) or placebo (n = 319) every 21 days. All patients received capecitabine or 5-FU plus cisplatin for up to six cycles. Patients continued capecitabine plus ramucirumab or placebo until progressive disease, toxicity or other discontinuation criteria.
PFS served as the primary endpoint for the first 508 patients. OS for the intent-to-treat population served as a secondary endpoint.
PFS appeared significantly prolonged among patients treated with ramucirumab plus capecitabine or cisplatin compared with placebo plus capecitabine or cisplatin (median, 5.7 months vs. 5.4 months; HR = 0.75; 95% CI, 0.61-0.94), meeting the study’s primary endpoint.
Researchers observed no survival benefit for patients treated with ramucirumab compared with placebo (median, 11.2 months vs 10.7 months; HR = 0.96; 95% CI, 0.8-1.16).
Overall response rate in the intent-to-treat population was 41.1% (95% CI, 35.8-46.4) in the ramucirumab arm and 36.4% (95% CI, 31.1-41.6) in the placebo arm.
At least 10% of patients in the ramucirumab arm reported grade 3 or greater adverse events that included neutropenia (26.3% ramucirumab vs. 27% placebo), anemia (12.1% vs. 14%), and hypertension (9.9% vs. 1.6%). – by Chuck Gormley
Disclosures: Eli Lilly funded the study. Fuchs reports consultant/advisory roles with Agios, Bayer, Dicerna, Eli Lilly, Entrinsic Health, Five Prime Therapeutics, Genentech/Roche, Gilead Sciences, KEW, Merck, Merrimack, Sanofi and Taiho Pharmaceutical. Please see the abstract for all other authors’ relevant financial disclosures.