OBJECTIVES: Novel combination therapies can improve survival compared with chemotherapy alone in patients with advanced NSCLC. However, acceptable tolerability is also important as it affects clinical outcomes, quality of life, and overall cancer treatment costs. This analysis assesses direct medical costs for the management of grade 3/4 adverse events (AEs) associated with two non-chemotherapies for first-line treatment of NSCLC consisting of either Bevacizumab (BEV) plus chemotherapy (CT) or Cetuximab (C) plus cisplatin/vinorelbine (CV). METHODS: Information on AE profiles were retrieved from the AVAiL study (7.5 mg/kg, Reck et al. 2009) and the E4599 study (15 mg/kg, Sandler et al. 2006) for BEV+CT and from the FLEX study (Pirker et al. 2009) for C+CV. To account for the inclusion of ECOG 2 patients in FLEX (which were excluded in AVAiL and E4599), incidences of febrile neutropenia, non-febrile neutropenia and leukopenia in FLEX were decreased by up to 30% based on expert suggestion to improve study comparability. Information on standard treatment patterns of the different AEs was collected through a systematic literature search and complemented by data provided by two German oncologists. These resource use items were assigned unit costs (charges) applicable to Germany. RESULTS: When unadjusted incidences of all AEs reported in AVAiL, E4599, and FLEX are used, resulting overall per-patient treatment costs related to the two BEV+CT studies are substantially lower those related to C+CV (€1092 and €464 versus €2287). Sensitivity analyses provide evidence that overall AE costs remain lower for AVAiL and E4599 even when incidences for selected AEs affected by cetuximab therapy are reduced by 10%, 20%, and 30% (€2151, €2015, and €1879, respectively). CONCLUSIONS: BEV+CT shows better tolerability linked with lower AE treatment costs when compared to C+CV. These favorable outcomes for BEV+CT were maintained when AE frequencies for C+CV were adjusted for ECOG status.