Comparison of First-Line FOLFOX versus FOLFIRI in RAS Mutant Metastatic Colorectal Cancer Patients

Objective: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality, with rat sarcoma (RAS) and proto-oncogene B-raf (BRAF) mutations associated with worse prognosis in metastatic settings.Despite advances in treatment, the optimal chemotherapy backbone combined with bevacizumab in RAS/BRAF-mutant metastatic CRC remains unclear.Our study aimed to investigate the best chemotherapy backbone in this patient group. Material and Methods:This retrospective study compared the efficacy and safety of first-line infused 5-fluorouracil, folinic acid and oxaliplatin (mFOLFOX6)+bevacizumab versus infused 5-fluorouracil, folinic acid and irinotecan (FOLFIRI)+bevacizumab in patients with RAS/BRAF-mutant metastatic CRC treated between November 2016 and January 2024.Overall survival (OS), progression-free survival, and clinical characteristics were evaluated.Statistical analyses included Kaplan-Meier survival estimates, Cox regression models, and subgroup analyses.Results: Among 130 patients, the median OS was significantly longer in the mFOLFOX6+bevacizumab group [22.6 months, 95% confidence interval (CI): 16.0-29.2]compared to the FOLFIRI+bevacizumab group (15.8 months, 95% CI: 10.7-20.8).ECOG performance status and chemotherapy backbone were significant prognostic factors for OS.Subgroup analysis revealed that patients with Eastern Cooperative Oncology Group performance status 2-4, and those with de novo metastases had worse outcomes, while younger patients (<60 years) benefited more from FOLFIRI+bevacizumab.Conclusion: mFOLFOX6+bevacizumab demonstrated superior survival outcomes compared to FOLFIRI+bevacizumab in first-line treatment of RAS/ BRAF-mutant metastatic CRC.These findings highlight the need for further randomized, prospective trials to validate these results and inform treatment strategies for this challenging patient population.