Initial treatment with FOLFOXIRI plus bevacizumab, rather than FOLFIRI plus bevacizumab, improved progression-free survival in adults with inoperable metastatic colorectal cancer participating in a phase III randomized clinical trial, according to a report published online Oct. 23 in the New England Journal of Medicine.
However, patients who received FOLFOXIRI developed more grade 3 or 4 adverse events such as neutropenia, diarrhea, stomatitis, and peripheral neuropathy. The trial assessed treatment efficacy but not quality of life, so the impact of these toxicities was not addressed, said Dr. Fotios Loupakis of the University of Pisa and his associates in the Triplet plus Bevacizumab (TRIBE) trial.
Dr. Fotios Loupakis
In the open-label study, patients with unresectable metastatic colorectal cancer who had not received chemotherapy or biologic therapy for their metastatic disease were treated at 34 medical centers across Italy. They were randomly assigned to receive up to 12 cycles of either the experimental treatment FOLFOXIRI (fluorouracil plus leucovorin and irinotecan and oxaliplatin) plus bevacizumab (252 patients) or the control treatment FOLFIRI (fluorouracil plus leucovorin and irinotecan) plus bevacizumab (256 patients). Both study groups then received maintenance therapy with fluorouracil plus bevacizumab until the cancer progressed or they withdrew from the study.
After a median follow-up of 32 months (range, 24.7-40.6 months), the primary outcome measure, progression-free survival, was 12.1 months with the experimental therapy, which was significantly longer than the 9.7 months in the control group (hazard ratio, 0.75) was. In addition, the treatment response rate was 12% higher and median overall survival was 5 months longer in the experimental group, the investigators said (N. Engl. J. Med. 2014 Oct. 23 [doi:10.1056/NEJMoa1403108]).
The percentage of bevacizumab-related adverse events was not significantly different between the two study groups, which indicates that intensifying the chemotherapy doesn’t affect the safety profile of the antiangiogenic agent. The rate of adverse events was significantly higher in the experimental-therapy group, but the rate of serious adverse events was similar (20.4% with FOLFOXIRI and 19.7% with FOLFIRI), as was the number of patients who died from adverse events (6 and 4, respectively).