5 or 25mg (Sutent SmPC), suggesting that lower doses of sunitinib are better tolerated than the recommended dose, which would presumably also reduce adverse event management costs. However, recent evidence shows that PFS and ORR with sunitinib correlate with drug exposure (Mendel et al, 2003; Houk et al, 2007), suggesting that dose reduction below a figure 2 certain threshold may reduce efficacy and thereby potentially affect patient outcomes. This study considered the cost of adverse event management for bevacizumab plus IFN and sunitinib in the United Kingdom, Germany, France and Italy. The average adverse event management costs varied across these countries but showed an overall trend of consistently lower costs for bevacizumab plus IFN versus sunitinib.

Management costs varied between the countries, but country-specific cost calculations/tariff lists provide a probable explanation. In addition, direct costs from a prospective study may be needed to confirm the cost savings observed in this study. The linear decision analytical model used in this study used health-care costs according to standard clinical practice from a variety of sources and relied on adverse event data from individual clinical trials that may not be fully comparable or reflective of adverse events in daily clinical practice. In addition, the linear decision analytical model did not permit a statistical analysis of the cost differences between sunitinib and bevacizumab plus IFN nor did it permit an analysis of the effect of adverse events on treatment efficacy; additional studies may be needed to confirm these data.

The study also highlights that there is no standardisation of treatment methods or costs across different countries, meaning that the potential effect of adverse event management costs should be assessed on an individual country basis. The poorly defined pathophysiology and management strategies of many sunitinib-associated adverse events may not have been captured by this analysis, that is, the potential of having to try different management approaches to identify the most effective may represent increased ��hidden’ costs. Moreover, the analysis used costs for the management of haematological adverse events and hand-foot syndrome based on historical chemotherapy-associated costs. This could have underestimated the costs of managing sunitinib-associated adverse events. However, the utilisation of chemotherapy-associated costs will remain the standard approach until specific GSK-3 data for targeted therapies are available. Finally, this study did not consider drug administration costs or initial drug acquisition costs because country-specific initiatives may result in significant cost differences, making standardisation across countries difficult.