Management of metastatic renal cell carcinoma progressed after sunitinib or another antiangiogenic treatment.

Prognosis of metastatic renal cell carcinoma (mRCC) has markedly improved in the recent years. Several factors such as precocious diagnosis, better supportive care, and an increased number of targeted therapies are responsible for this progress. From 2006 to date, 7 drugs have been approved for treatment of mRCC, and among these only 2 are recommended for the second line of therapy with grade 1 evidence. Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors are the strategies with more evidence, but no comparative studies are available and what is the best second line remains an open issue. Herein, we review the available evidence on the second-line treatment focusing mainly on prospective studies. We identify a special population of patients in whom more evidence is available, and we propose a possible strategy for the management of progressed mRCC and for primary resistant lesions as well as for patients who need a rapid response in lesions. In the majority of patients, several factors should be considered: toxicity reported during first-line therapy, performance status, the absence of correlation between the length of first-line therapy and the probability to respond to second-line therapy, and the lack of comparative trials between mTOR inhibitors and TKI. When an mTOR inhibitor is selected, everolimus must be preferred, although in the RECORD1 trial only the increase in progression-free survival has been reported and the increase in terms of overall survival has not been reached. When another TKI is the choice, there are no strong pieces of evidence that favor the use of a defined molecule. In every case, we recommend to start the selected targeted agents at standard dosage and to pursue therapy as long as possible because the control of disease should be the primary endpoint for the management of mRCC.