On April 24, 2015, the U. S. Food and Drug Administration approved ramucirumab (CYRAMZA®, Eli Lilly and Company) for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Ramucirumab is a recombinant human monoclonal IgG1 antibody that binds to the human vascular endothelial growth factor- receptor 2 (VEGF-R2), preventing the interaction of VEGF-R2 to its ligands.
This approval is based on the results of a randomized, double-blind, multinational trial enrolling patients with mCRC that progressed during or within 6 months of discontinuation of bevacizumab-, oxaliplatin- and fluoropyrimidine-based combination chemotherapy.
The clinical trial accrued 1072 patients who were randomly allocated (1:1) to receive FOLFIRI plus placebo or FOLFIRI plus ramucirumab (N=536 per arm). Treatment cycles on both arms were repeated every 2 weeks and ramucirumab was administered at a dose of 8 mg/kg by intravenous infusion every two weeks. Ramucirumab was continued until disease progression or unacceptable toxicity.
The primary efficacy endpoint was overall survival (OS). Treatment assignment was stratified by geographic region (North America vs. Europe vs. other regions), KRAS status (wild-type vs. mutant) and time to progression for the beginning of first-line treatment (< 6 months vs. greater than or equal to 6 months).
The median age of the study population was 62 years, 57% were men, and 99% had an ECOG performance status of 0 or 1. A statistically significant OS improvement was observed in patients receiving FOLFIRI plus ramucirumab compared to those receiving FOLFIRI plus placebo