Recent studies combining PD-1/L1 inhibitors with either the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor axitinib or the anti-CTLA-4 antibody ipilimumab have demonstrated improved objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS) compared with sunitinib.1–4 Given these results, most patients with clear cell renal cell carcinoma (ccRCC) will receive a PD-1/L1 inhibitor-based regimen either in combination with axitinib or, if intermediate or poor-risk disease, ipilimumab, as first-line therapy. This evidence concerns the gene VEGFA and nonpapillary renal cell carcinoma.