Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of 
the serial administration of single agents. Combinations of VEGF and mTOR 
inhibitors have been disappointing in previous randomized trials. However, the 
combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as 
FGF receptors, and everolimus demonstrated promising results in a randomized 
phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and 
programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation 
of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte 
antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction 
with the development of predictive biomarkers and agents inhibiting novel 
therapeutic targets may provide much needed advances in this still largely 
incurable disease.