Sequential use of targeted agents in the treatment of renal cell carcinoma

Sequential use of targeted therapies is a common practice in the treatment of advanced renal cell carcinoma (RCC) that extends disease control beyond the benefit of single therapies. After disease progression on one agent, treatment with a second targeted agent as subsequent-line therapy provides disease control and additional progression-free survival. The most effective sequence of targeted agents has yet to be determined. Results from the only trial of sequenced targeted agents support the use of mammalian target of rapamycin inhibitors after resistance develops to vascular endothelial growth factor (VEGF) inhibitors. Preliminary data suggest an antitumor effect of VEGF-targeted therapy in RCC, despite prior exposure to other VEGF-targeted therapies. The safety and efficacy of sequential therapies are currently under investigation; the optimal sequence may vary among patients to accommodate comorbid conditions or different disease stages. The current evidence supporting sequential use of targeted agents in RCC is presented in this review.