Targeted therapy in the treatment of metastatic renal cell cancer

The treatment of metastatic renal cell carcinoma (MRCC) has evolved from being predominantly cytokine-based to being grounded in the use of drugs targeting vascular endothelial growth factor, platelet-derived growth factor and mammalian target of rapamycin (mTOR) pathways. New agents including the small-molecule targeted inhibitors sunitinib, sorafenib and temsirolimus and the monoclonal antibody bevacizumab have shown anti-tumor efficacy and have become the standard of care for most patients. Sunitinib and temsirolimus have shown significant improvements in overall survival (OS), in the first-line setting, when compared with interferon. Sorafenib has demonstrated prolonged progression-free survival (PFS) in a phase III study in comparison with placebo in the second-line setting. More recently, two phase III studies have compared bevacizumab and interferon with interferon alone. Both studies showed a statistically significant improvement in PFS for the combination arm but no difference in OS. Everolimus showed prolonged PFS in the second/third-line setting. Pazopanib prolongs PFS in naïve/cytokine refractory patients. Immunotherapy confers a small but significant OS advantage but only for the minority of patients with good prognostic features. The results of these trials and ongoing efforts to improve treatment of MRCC are the focus of this review.