Second-line therapy for refractory renal-cell carcinoma

In the last 5 years inhibitors of the VEGF/VEGFR and mTOR pathways have dramatically changed the therapeutic approach to metastatic renal cancer. Randomized controlled trials have shown that six targeted agents - sorafenib, sunitinib, temsirolimus, bevacizumab, everolimus and pazopanib - are able to improve patient outcome. Even if the choice of drug for first-line therapy is quite well defined, to date it is not easy to characterize and evaluate the efficacy of new therapies in second-line treatment. It is not clear whether, after first-line therapy with a VEGF/VEGFR inhibitor, use of mTOR or a second TKI inhibitor should be recommended. In this review we report on current evidence supporting the use of targeted agents in second-line therapy. Therefore we try to combine current clinical results with a practical clinical approach, with the goal of evaluating the best clinical decision for different clinical situations.