New therapies in renal cell carcinoma

We present an update on the dramatic changes that have occurred over the past year in the management of patients with metastatic renal cell carcinoma.

Although it was demonstrated that benefit from immunotherapy is restricted to a minority of patients, a better understanding of the molecular mechanisms involved in the pathogenesis of clear cell carcinoma has led to development of multiple targeted therapies, with significant clinical benefits. Two compounds that predominantly inhibit the tyrosine kinase activity of vascular endothelial growth factor receptor have been demonstrated to improve the progression-free survival of patients as first-line (sunitinib versus interferon-alpha) or second-line (sorafenib versus placebo) treatment. Temsirolimus, which inhibits the serine-threonine kinase activity of the mammalian target of rapamycin, offers better overall survival than interferon in patients with poor risk characteristics. Finally, bevacizumab combined with interferon is yielding substantial response rates and increased progression-free survival compared with interferon alone.

Four major drugs or regimens with proven efficacy are now available for first-line and second-line therapy in metastatic renal cell carcinoma. Further studies are needed to determine the optimal combinations of these agents in metastatic disease and to assess their impact in the adjuvant setting.