OBJECTIVES: First-line chemotherapy for locally-advanced or metastatic non-small cell lung cancer (mNSCLC) is usually limited to 4-6 cycles, as prolonged exposure leads to cumulative toxicity without additional survival benefit. Maintenance therapy represents a new treatment option which can delay disease progression and extend survival in patients with mNSCLC. Erlotinib and pemetrexed are currently the only treatments specifically approved for this indication by the European Medicines Agency and US Food and Drug Administration; therefore, it is important to compare the monthly treatment costs of using erlotinib or pemetrexed for the maintenance therapy of patients with mNSCLC. METHODS: Italian monthly treatment costs were calculated as the sum of the ex-factory costs for the average dose (erlotinib = 150 mg/day, pemetrexed = 500 mg/m2) over a 30-day treatment duration plus administration costs. Monthly administration costs were derived from regional tariffs for oncology drugs. RESULTS: Monthly drug costs for erlotinib maintenance therapy are lower than for pemetrexed (€1517 versus €2770, respectively). In addition, as an intravenous treatment, pemetrexed is associated with additional costs related to administration (estimated at €140 per month); whereas, orally-administered erlotinib is not associated with any administration costs. Pemetrexed total monthly treatment costs are therefore €2910, €1393 higher than erlotinib total monthly treatment costs. The cost saving associated with erlotinib would allow approximately 92% more patients to be treated with erlotinib maintenance therapy, based on a fixed healthcare budget. Furthermore, it is anticipated that the management of pemetrexed-related adverse events (e.g. neutropenia, anaemia) would be more costly than those related to erlotinib use (e.g. rash, pruritus). Therefore, the cost saving when using erlotinib versus pemetrexed for first-line maintenance therapy may be greater in a real-world setting. CONCLUSIONS: Based on Italian costs, erlotinib is a cost-saving treatment option compared with pemetrexed, for the first-line maintenance therapy of patients with locally-advanced or mNSCLC.