Optimizing treatment of metastatic renal cell carcinoma by changing mechanism of action

Abstract

Novel targeted agents, such as VEGF receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and mTOR inhibitors, have improved therapy for metastatic renal cell carcinoma. Sequential administration of agents with similar mechanisms of action has shown some efficacy in small retrospective studies; however, prospective Phase II studies have reached differing conclusions, and there is a current lack of prospective randomized data to validate this approach. Sequential administration of agents with different mechanisms of action has shown clinical efficacy in prospective trials, including a randomized Phase III study (RECORD-1) of the mTOR inhibitor everolimus, the only targeted agent recommended for use after VEGFR-TKI failure in metastatic renal cell carcinoma. Ongoing research will further define the relative merits of other sequences in terms of clinical outcome.