To perform a cost-effectiveness analysis of Panitumumab+FOLFOX as first-line treatment in mCRC WT-RAS patients compared to Cetuximab+FOLFIRI. A seven health stages Markov Model (progression-free, metastasis resection, second-line progression, palliative care, no-progression after resection, progression after resection, and death) were evaluated in two-week transition cycles in a lifetime scenario. Since no head to head trials have been conducted comparing Panitumumab and Cetuximab in first line treatment of WT RAS patients, an indirect comparison was performed to obtain the relative Progression-free survival (PFS) and global survival (OS) between both epidermal growth factor receptor inhibitors (anti-EGFR). By linking PEAK and FIRE-3 trials (assuming that FOLFOX and FOLFIRI are equal) via a common evidence base (in this case Bevacizumab). Parametric survival modeling was used to extrapolate beyond the data collection period. The resource use and treatment patterns were obtained from three oncologists through a modified Delphi panel. Costs include testing for RAS mutation status; drug administration, chemotherapy, clinician visits, and diagnostic tests; treating grade 3/4 toxicities; metastasis resection; second-line treatment; and palliative care. For all procedures Social Security cost (ISS+30) were applied; and SISMED prices for drugs. Clinical costs and benefits are discounted 5% per annum. The mean discounted OS derived from the model was 45.3 and 41.8 months with Panitumumab+FOLFOX6 and Cetuximab+FOLFIRI respectively; and a mean discounted PFS of 14.8 and 10.8 months. The total average cost with Panitumumab is USD$81,522.32 and USD$80,241.83 with Cetuximab. The longer predicted survival for a patient treated with Panitumumab result in a lower cost per life-year (LY) (USD$21,613.42) compared to Cetuximab (USD$23,036.94). Based on the adjusted PEAK-FIRE3 results, Panitumumab showed treatment outcomes improvement vs Cetuximab for WT-RAS patients at a lower cost per life year.