Future developments in renal cell carcinoma.

BACKGROUND The development of targeted agents has substantially improved prognoses for patients with metastatic renal cell carcinoma (mRCC). Four targeted agents are approved for the treatment of mRCC in Europe (bevacizumab given in combination with interferon-alfa, sorafenib, sunitinib and temsirolimus) and a number of investigational agents have shown potential in this setting. DESIGN This report will review completed and ongoing clinical trials in mRCC designed to investigate the efficacy of targeted agents in sequential and combination therapies and in the adjuvant and neoadjuvant settings. RESULTS A phase III trial, in which 71% of patients received prior sunitinib treatment, has indicated that everolimus can be used after sunitinib, the reference standard of care for first-line therapy, to extend progression-free survival. Phase I/II studies have provided preliminary data on the efficacy of sequential and combination therapies with targeted agents in mRCC. Several phase III studies investigating targeted agents in sequential and combination therapies and in the adjuvant and neoadjuvant settings are planned or ongoing, and data are awaited with interest. CONCLUSIONS Data suggest that sequential and combination therapies with targeted agents have potential in patients with mRCC. Ongoing research will help to optimise the use of targeted therapies in this setting.