PURPOSE OF REVIEW: Multiple agents, including vascular endothelial growth factor 
(VEGF) inhibitors and mammalian target of rapamycin inhibitors have been 
approved over the past decade for the treatment of metastatic renal cell 
carcinoma (mRCC). Here, we focus on nivolumab, cabozantinib, and lenvatinib plus 
everolimus, agents that have recently emerged with positive clinical data 
leading to 'Food and Drug Administration approval or pending approval in mRCC. 
We also review the development of novel agents of interest showing promise in 
mRCC as part of combination therapy'.
RECENT FINDINGS: Nivolumab and cabozantinib both offer improved survival over 
everolimus in the second-line treatment of mRCC. Lenvatinib plus everolimus has 
similarly shown encouraging survival benefits in a phase II trial for the 
second-line setting. Novel combinations in mRCC, including dual immune 
checkpoint blockade, VEGF and programmed death 1 inhibition, VEGF and vaccine 
therapy, dual angiogenic blockade, and VEGF-directed therapy with 
nanoparticle-containing camptothecin have shown promising activity in 
early-phase trials.
SUMMARY: Multiple promising agents are available in the treatment of mRCC. The 
appropriate sequencing of agents in the treatment of mRCC may become further 
elucidated by future studies that prospectively analyze potential biomarkers to 
identify patients who will derive the greatest benefit from VEGF, mammalian 
target of rapamycin, or checkpoint inhibitors.