Clinical Trial Overview
The FIRE-4.5 (AIO KRK0116) study, a randomized phase II clinical trial, investigated the efficacy of combining FOLFOXIRI (a triplet chemotherapy regimen consisting of fluorouracil, folinic acid, oxaliplatin, and irinotecan) with either cetuximab or bevacizumab as first-line treatment for patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC). This study aimed to address the poor outcomes associated with the BRAFV600E mutation in mCRC.
Patients and Methods
A total of 109 patients were randomly assigned, with 107 included in the full analysis set (FAS). Patients were allocated in a 2:1 ratio to receive either FOLFOXIRI plus cetuximab (experimental arm, n = 72) or FOLFOXIRI plus bevacizumab (control arm, n = 35). The primary endpoint was the objective response rate (ORR) according to RECIST 1.1 criteria, evaluated in the ATP (according to protocol) population. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and feasibility.
Results
In the ATP population of 89 patients, the ORR was 51% in the cetuximab-based experimental arm and 67% in the bevacizumab-based control arm. The median PFS was significantly inferior in the experimental arm (6.7 months vs. 10.7 months; hazard ratio [HR], 1.89; P = .006). Median OS, analyzed at an event rate of 64.5%, showed a trend toward shorter survival in cetuximab-treated patients (12.9 months vs. 17.1 months; HR, 1.4; P = .20).
Conclusion
The FIRE-4.5 study is the first prospective and randomized trial to investigate first-line treatment options for BRAFV600E-mutant mCRC. The findings suggest that FOLFOXIRI plus cetuximab does not induce a higher ORR compared to FOLFOXIRI plus bevacizumab in this patient population. Consequently, bevacizumab-based chemotherapy remains the preferable first-line treatment for patients with BRAFV600E-mutant mCRC.
