First-Line FOLFOXIRI Plus Bevacizumab for Patients With Metastatic Colorectal Cancer

According to results from a real-world study, first-line FOLFOXIRI plus bevacizumab demonstrated improved efficacy compared to doublets plus bevacizumab among patients with initially unresectable, liver-only, right-sided and or RAS or BRAF V600E-mutated metastatic colorectal cancer (mCRC). 

“Upfront FOLFOXIRI/bevacizumab is associated with better outcome over doublets/bevacizumab in [mCRC], independently of the presence of liver-only disease and the secondary resection of metastatic lesions,” stated Carlotta Antoniotti, University of Pisa, Italy, and coauthors. “Limited data are available about the comparison of these two regimens in patients with initially unresectable liver-only mCRC who represent the optimal candidates according to primary tumour sidedness and/or RAS and BRAF mutational status.” 

In this study, researchers collected data from 300 patients with initially unresectable, liver-only, right-sided and/or RAS or BRAF V600E-mutated mCRC enrolled across 4 phase 2/3 trials. Patients had received either first-line FOLFOXIRI (n = 170) or doublets (n = 130) plus bevacizumab. Primary end points included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), safety, and R0 resection rate. 

At a median follow-up of 40.1 months, median PFS was 12.3 months in patients treated with FOLFOXIRI and bevacizumab and 10.3 months in patients treated with doublets and bevacizumab (P = .019). Median OS was 29.1 months in patients treated with FOLFOXIRI and bevacizumab and 23.3 months in patients treated with doublets and bevacizumab (P = .253). The ORR rates were 64% and 53%, respectively (P =. 076). Treatment with FOLFOXIRI and bevacizumab was associated with higher rates of grade 3/4 neutropenia (44%) and diarrhea (19%). The R0 resection rate was 27% in patients treated with FOLFOXIRI and bevacizumab and 24% in patients treated with doublets and bevacizumab (P = .696). There was no correlation between treatment effect and R0 resection.

“As compared to doublets/bevacizumab, FOLFOXIRI/bevacizumab provides a meaningful PFS and ORR advantage among patients with initially unresectable, liver-only, right-sided and/or RAS or BRAFV600E [mutated] mCRC, independently of achieving R0 resection or not, thus corroborating the choice of this regimen as upfront treatment for these patients,” concluded Dr Antoniotti et al. 

Source: 

Antoniotti C, Marmorino F, Rossini D, et al. FOLFOXIRI/bevacizumab versus doublets/bevacizumab as initial therapy of unresectable liver-only, right-sided and/or RAS or BRAF mutated metastatic colorectal cancer: An individual patient data-based pooled analysis of randomized trials. Eur J Cancer. Published online: August 15, 2025. doi: 10.1016/j.ejca.2025.115713