OBJECTIVES: Bevacizumab (Bev) has been shown to increase progression free survival (PFS) when combined with cisplatin-gemcitabine (Reck 2009) and PFS and overall survival in combination with carboplatin-paclitaxel (Sandler 2006) when compared with chemotherapy (CT) alone. Cetuximab (Cet) has also improved outcomes in these patients when combined with vinorelbine and cisplatin (VinCis) (Pirker 2009). The aim of this analysis is to compare the administration costs of Bev+CT and CetVinCis therapy for mNSCLC patients in France, Germany, and Spain. METHODS: A systematic literature search performed in Medline, Embase, Cochrane, and Centre for Reviews and Dissemination databases identified 578 publications which included administration costs. Two independent reviewers selected sixteen full text publications for inclusion. In addition, an evaluation of national reimbursement tariffs in both inpatient and outpatient settings was performed. Alongside this, in-depth semi-structured interviews were conducted with five expert oncologists in three countries to verify cost findings and reimbursement structures. RESULTS: For induction therapy, when comparing CetVinCis versus BevPacCarbo or BevGemCis respectively, the incremental administration cost per mNSCLC patient is an additional €4500/€2250 in France, €7320/€3660 in Germany, and €3960/€1980 in Spain for the CetVinCis combination vs administration costs for the Bev combinations. When considering additional maintenance monotherapy the difference is €6,375/€4,125 in France, €10,370/€6,710 in Germany, and €5,610/€3,630 in Spain with again higher costs associated with the CetVinCis combination vs the Bev combinations. Variation in cost is attributable to increased number of patient visits and disparities in reimbursement structures. CONCLUSIONS: Additional injection visits associated with CetVinCis therapy (weekly for cetuximab vs once every three wekks for Bev) are a cost driver in the treatment of mNSCLC. BevPacCarbo or BevGemCis when compared with CetVinCis offers a less often and more convenient dosing regime, while also incurring fewer administration costs.