The future of tyrosine kinase inhibitors: single agent or combination?

The past 3 years have delivered positive phase 3 trial results for sorafenib, sunitinib, temsirolimus, and bevacizumab in renal cell carcinoma (RCC). The benefit of these therapies has been best defined as either first-line therapy or following cytokine therapy in patients with clear cell RCC. In light of the differences in the molecular targets of each agent, there is reason to believe that sequential single-agent therapy or regimens combining these agents could extend the benefits observed in the reported randomized trials. However, to date, few data have been reported supporting either strategy. A careful consideration of the specific mechanism of action of each agent provides a basis for considering the optimal therapeutic strategies for incorporating each of these agents into the management of metastatic RCC.