• bevacizumab
• metastatic colorectal cancer
• triplet

BACKGROUND
Fluoropyrimidine-based associations with irinotecan or oxaliplatin, combined with the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, are an accepted standard in the first-line treatment of metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) had demonstrated superior activity and efficacy compared to fluorouracil and irinotecan (FOLFIRI). The combination of FOLFOXIRI plus bevacizumab was investigated in a phase 2 study showing promising activity and manageable toxicities.
METHODS
We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Treatments were administered up to 12 cycles followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.
RESULTS
The median progression-free survival was 12.1 months in the experimental arm, as compared with 9.7 months in the control arm (hazard ratio for progression, 0.75; 95% confidence interval, 0.62 to 0.90; P=0.003). The objective response rate was 65% in the experimental arm, as compared with 53% in the control arm (P=0.006). Longer overall survival was reported with FOLFOXIRI plus bevacizumab (31.0 vs. 25.8 months, hazard ratio for death, 0.79; 95% confidence interval, 0.63 to 1.00; P=0.054). Grade 3-4 neurotoxicity, stomatitis, diarrhea and neutropenia were significantly increased in the experimental arm.
CONCLUSIONS
The study met its primary endpoint. FOLFOXIRI plus bevacizumab improves the outcome of metastatic colorectal cancer patients with a manageable increase in specific adverse events.