S363 Efficacy and Safety of FOLFOXIRI Plus Cetuximab Versus FOLFOXIRI Plus Bevacizumab for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Introduction: Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality worldwide. Intensified chemotherapy with FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) combined with targeted agents has shown promising outcomes in mCRC patients. This meta-analysis compares the efficacy and safety of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab in patients with mCRC to inform clinical decision-making and personalized treatment. Methods: A literature search was conducted across PubMed, Cochrane, Embase, Scopus, and clinicaltrials.gov from inception till February 2025. Four studies evaluating FOLFOXIRI plus cetuximab vs FOLFOXIRI plus bevacizumab were included. Analysis was performed using R Studio version v4.4.5. Pooled outcome estimates are reported as mean difference (MD), hazard ratio (HR), and odds ratio (OR), and 95% confidence interval (CI) using the random effect model. Statistical heterogeneity was assessed using I² and X² statistics. Results: Four studies with 561 patients were included in our study. Overall survival between FOLFOXIRI plus cetuximab vs FOLFOXIRI plus bevacizumab was not statistically significant (HR: 1.22; 95% CI: 0.78 –1.90; P = 0.386, I² = 49%). Progression-free survival (PFS) was significantly higher in the cetuximab arm (HR: 1.79; 95% CI: 1.21-2.63; P = 0.003; I² = 0%). Objective response rate, complete response, and partial response also did not differ significantly [(OR: 1.48; 95% CI: 0.58 – 4.93; P = 0.4772; I2 = 66.7%), (OR: 1.59; 95% CI: 0.66-3.86; I² = 0%), and (OR: 1.60; 95% CI: 0.5, P = 0.62; I2 = 73%) respectively]. Depth of response showed no significant difference (MD: 15.29; 95% CI: -1.35–31.94; P = 0.07). Hypomagnesemia and rash acneiform were the most notable adverse events with cetuximab (P < 0.01). However, alopecia, anemia, neurotoxicity, and stomatitis showed no difference between the 2 arms. Conclusion: FOLFOXIRI plus cetuximab improved PFS in patients with mCRC but showed no significant overall survival and response rates than the bevacizumab combination; however, with increased toxicity. Treatment should be personalized based on tumor biology and patient tolerance.