The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) 
has dramatically changed with the introduction of targeted agents including 
vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new 
agents including growth factor receptor antagonists and a checkpoint inhibitor 
were approved for the treatment of refractory metastatic RCC based on 
encouraging benefit shown in clinical trials. Areas covered: The background and 
biological rationale of existing treatment options including a brief discussion 
of clinical trials which led to their approval, is presented. This is followed 
by reviewing the limitations of these therapeutic options, medical need to 
develop new treatments and major goals of ongoing research. We then discuss two 
recently approved growth factor receptor antagonists i.e. cabozantinib and 
lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues 
pertaining to drug development, and future directions in treatment of metastatic 
RCC. Expert opinion: Recently approved growth factor receptor antagonists have 
shown encouraging survival benefit but associated drug toxicity is a major 
issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has 
similarly shown survival benefit and is well tolerated. With multiple options 
now available in this patient population, the right sequence of these agents 
remains to be determined.