Randomized phase 2 trial of first-line FOLFOXIRI plus cetuximab versus bevacizumab for metastatic colorectal cancer with BRAF-V600E mutation

BRAF^V600E mutation is associated with poor outcomes in metastatic colorectal cancer (mCRC). The multicenter randomized phase 2 FIRE-4.5 trial in Germany compared addition of cetuximab versus bevacizumab to first-line FOLFOXIRI for BRAF^V600E mutated mCRC. The ORR was 51% in the cetuximab arm versus 67% in the bevacizumab arm (p=0.92). The median PFS was signficantly worse with cetuximab compared with bevacizumab while the median OS was nonsignificantly worse with cetuximab compared with bevacizumab. The authors conclude that bevacizumab-based chemotherapy remains the preferable first-line treatment of patients with BRAFV600E-mutated mCRC.