FOLFOXIRI plus cetuximab does not improve survival or response rates compared to bevacizumab in mCRCTrial Shows No Difference Between Two Colorectal Cancer Treatments

INTRODUCTION: Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality worldwide. FOLFOXIRI combined with targeted agents has shown promising outcomes in mCRC. This meta-analysis compares efficacy and safety of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab in patients with mCRC. METHODS: A literature search was conducted across PubMed, Cochrane, Embase, Scopus, and clinicaltrials.gov until February 2025. Analysis was performed using RStudio v4.5.0. Pooled estimates are reported as hazard ratios, odds ratios, risk ratios, and mean difference with 95% CIs using random-effects model. Heterogeneity was assessed using I² statistics. RESULTS: Four studies (3 RCTs, 1 observational) comprising 561 patients were included. Overall survival did not differ significantly between FOLFOXIRI-cetuximab and FOLFOXIRI-bevacizumab (HR: 1.22; 95% CI: 0.78 - 1.90; p = 0.386). Progression-free survival also did not differ significantly (HR: 1.32; 95% CI: 0.76-2.31; p = 0.324). Objective response rate, complete response, and partial response did not differ significantly [(OR: 1.48; 95% CI: 0.50-4.37; p = 0.4772), (OR: 1.59; 95% CI: 0.66-3.86; p = 0.303), and (OR: 1.60; 95% CI: 0.52-4.93, p = 0.414) respectively]. Depth of response showed no significant difference (MD: 15.29; 95% CI: -1.35-31.94; p = 0.07). Hypomagnesemia and acneiform rash were significantly more frequent with cetuximab (p < 0.01). However, alopecia, anemia, neurotoxicity, and all-grade stomatitis showed no difference between the two arms. CONCLUSIONS: FOLFOXIRI-cetuximab did not improve PFS, OS, or response rates in patients with mCRC compared with the bevacizumab combination; however, it was associated with significantly higher rates of hypomagnesemia and acneiform rash.