OBJECTIVES: Eurtact trial was the first randomized phase III trial evaluating efficacy and safety of erlotinib vs chemotherapy in the first-line treatment of EGFR mut+ Caucasian patients. This trial showed an increase in the median PFS of 4,5 months with erlotinib vs chemotherapy. Based on this study, we aimed to assess the cost-effectiveness of erlotinib versus platinum based chemotherapy in the first-line treatment of advanced NSCLC patients with activating EGFR mutations. METHODS: A health economic cost-effectiveness analysis was developed incorporating a Markov model simulating the evolution of a cohort of advanced NSCLC patients with activating EGFR mutations. Three health states were included: Progression Free Survival (PFS), Progression and Death. The time horizon was 7 years. Outcomes were life years gained (LYG). Resource utilization related to each health state was estimated by a Spanish Expert Panel. Cost were expressed in € 2012 and include drug and administration costs, and drug-related adverse events management cost. This analysis was performed taking into account the Spanish National Health System’s perspective. Patient data on progression-free and overall survival were obtained from the EURTAC study. Probabilistic sensitivity analyses were conducted to incorporate parameter uncertainties. RESULTS: Erlotinib treated patients achieved a mean of 2.161 LYG compared to 1.555 LYG in patients receiving chemotherapy. Total mean treatment cost with erlotinib and chemotherapy was €22,458 and €5,335 respectively. The incremental cost-effectiveness ratio (ICER) per LYG was €28,261. Since erlotinib treatment is prolonged until disease progression and chemotherapy is stopped at 4 cycles, treatment duration is one of the cost-driver of the model. CONCLUSIONS: Erlotinib treatment of NSCLC patients with activating EGFR mutations is associated with an increased life expectancy and is a cost-effective therapeutic option in Spain.