FOLFOXIRI plus Bevacizumab or Anti-EGFR Antibodies in RAS/BRAF Wild-Type Metastatic Colorectal Cancer

Conference Correspondent - ESMO 2014 - Gastrointestinal and Head & Neck Cancer

Monoclonal antibodies (MoAbs) targeting vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) in combination with first-line doublet chemotherapy have demonstrated considerable clinical activity in metastatic colorectal cancer (mCRC). The fluoropyrimidine, folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) regimen is a highly active chemotherapy regimen in patients with mCRC that confers significantly more clinical benefit compared with doublet regimens. In the present analysis, Salvatore and colleagues sought to evaluate the efficacy of FOLFOXIRI plus the anti-VEGF MoAb bevacizumab, or the anti-EGFR MoAbs panitumumab and cetuximab, in RAS and BRAF wild-type patients with mCRC (Salvatore L, et al. ESMO 2014: Abstract 515P). The best response according to RECIST, early response, early tumor shrinkage (ETS), and the depth of response (DOR) in the 2 groups were analyzed.

In this retrospective analysis, the anti-EGFR cohort (n = 101) included patients treated with FOLFOXIRI plus panitumumab in the TRIP trial and FOLFOXIRI plus cetuximab in the MACBETH trial, whereas the bevacizumab cohort included patients treated with FOLFOXIRI plus bevacizumab in the TRIBE trial (n = 62), all of whom had RAS and BRAF wild-type genotypes. The response rate was numerically higher in the anti-VEGF cohort compared with the bevacizumab cohort (82% vs 71%; P = .120), but was not statistically significant. Similarly, early response was reported in 74% and 62% of the anti-EGFR and bevacizumab groups, respectively. However, the median ETS in the anti-EGFR group was significantly higher than in the bevacizumab group (40.8% vs 26.4%; P = .003). Also, the DOR was significantly higher in the anti-EGFR group versus the bevacizumab group (48.6% vs 37.8%; P = .005).

The investigators concluded that both FOLFOXIRI plus bevacizumab and FOLFOXIRI plus an anti-EGFR MoAbs resulted in high response rates in the first-line treatment of patients with RAS and BRAF wild-type mCRC, and that combination with anti-EGFR MoAbs may be associated with higher ETS and DOR.