OBJECTIVES: To demonstrate the pharmacoeconomic savings provided by panitumumab (Vectibix®), a fully human anti-EGFR monoclonal antibody (mAB) when compared with cetuximab (Erbitux®), a chimeric mAB, based on practical usage considerations in metastatic colorectal cancer (mCRC) patients, from the Italian Payers’ perspective. METHODS: The model demonstrated the annual savings provided by panitumumab versus cetuximab in a cohort of patients by grouping them into three distinct areas; low-weight patient savings, administration savings and safety savings. The products were compared based on dosing, administration and safety data from the product labels. Given the lower incidence of grade IV infusion reactions expected with panitumumab compared with cetuximab, safety savings were calculated by multiplying the comparative difference in frequency of infusion reactions by the Diagnosis-Related Group (DRG) for an anaphylactic shock. Administration savings compared the dosing schedules of panitumumab (biweekly) and cetuximab (weekly). Therapy visit costs were based on national tariffs (outpatient DRGs).  For the average patient, with a weight of 73kg and a surface area of 1.7m2, panitumumab and cetuximab are priced at parity. However, over a range of patients, the average cost for panitumumab will be lower. The model used the normal distribution and the mean and standard deviations for weight and surface area, gained from an Italian retrospective patient survey, to define the cohort and calculate average savings over different combinations of patient weight and surface area.  RESULTS: Savings of €3,404 per course per patient were shown; potentially saving the Italian healthcare system €7.67 million per year. This assumes that of the 2,252 third-line patients, 57% receive panitumumab and 43% receive Active Supportive Care in Year 1 based on the prevalence of the wild-type K-RAS mutation, compared with 100% receiving cetuximab.  CONCLUSIONS: Results indicate that substantial savings are associated with panitumumab therapy over cetuximab therapy at national and per-patient levels.