OBJECTIVES: Novel combination therapies for advanced NSCLC can offer improved survival over chemotherapy alone. Besides effectiveness new therapies must also demonstrate acceptable tolerability. Furthermore, toxicities can result in potentially high additional treatment costs. This analysis thus explores the treatment costs of adverse events (AEs) related to two newly available first-line NSCLC therapies consisting of either Bevacizumab (BEV) combined with chemotherapy (CT) or Cetuximab (C) combined with cisplatin + vinorelbine (CV). METHODS: All published AEs and their incidences as reported in the AVAiL trial (7.5 mg/kg, Reck et al. 2009) or the E4599 trial (15 mg/kg, Sandler et al. 2006) were taken into consideration for the BEV+CT analyses, whereas AE data for the C+CV regimen was retrieved from the FLEX trial (Pirker et al. 2009). A systematic literature search was performed to collect published information on standard treatment patterns and costs of AEs. Two oncologists in France were additionally interviewed to substantiate and complement the data on medical resource utilization for the AEs under study. These resource use items were then assigned unit costs (charges) based on tariffs for France. A model was subsequently developed and populated with the collected data to calculate total average per-patient AE costs associated with the two compared therapy regimens. RESULTS: Our analysis shows substantially lower overall per-patient treatment costs for the grade 3/4 AE profiles observed for both BEV regimens (cisplatin/gemcitabine; carboplatin/paclitaxel) than those for the severe AEs observed in the FLEX trial (€1,166 and €419 versus €2,236). The cost differences favouring BEV+CT are mainly attributable to lower incidences of febrile neutropenia, dyspnoea, anaemia, sepsis, and respiratory failure. CONCLUSIONS: BEV+CT shows better tolerability and lower AE treatment costs as compared to C+CV. Coupled with its favorable effectiveness, BEV+CT should be considered as therapy of choice for patients with advanced NSCLC.