Sequential medical therapy in renal carcinoma

Abstract

Renal cell carcinoma (RCC) is the ninth most common cancer in humans. In the last decade, a better understanding of the molecular mechanisms underlying tumorigenesis, angiogenesis, cell growth and proliferation, and the discovery of molecular alterations involved in RCC pathogenesis, have led to the identification of molecular targets of great clinical interest that have revolutionized the treatment of metastatic RCC (mRCC). Sunitinib, pazopanib and bevacizumab plus interferon-alpha remain the standard first-line treatments: these agents have significantly improved prognosis in mRCC. Everolimus, axitinib and sorafenib have demonstrated significant efficacy as second-line therapies. Nivolumab and cabozantinib are the most promising new-generation agents in the treatment of RCC. All of these agents, given in sequence, have extended life expectancy of RCC patients from 13 months in the cytokine era to over 20 months. Despite this improvement, it is not easy to establish the right sequence in which to administered different agents because there aren’t yet ways to identify or select patients likely to benefit or those who could be resistant to specific drugs. In this review we present clinical data on the sequential treatment in RCC and discuss key factors that need to be considered when physicians make treatment decisions for individual patients.