Combination Anti–PD-1 Therapy and VEGFR TKI in Heavily Treated Advanced Renal Cell Cancer

The initial management of most patients with metastatic clear-cell renal cancer is either dual immune checkpoint inhibitors (ICIs) or an ICI in combination with a vascular endothelial growth factor receptor–targeting tyrosine kinase inhibitor (VEGFR TKI). Some patients with disease progression following ICI-based therapy receive treatment with alternative TKIs; however, many clinicians will utilize other ICI-based combination therapies despite a lack of evidence to support this approach.

In an industry-sponsored phase 3 trial, investigators randomized 343 patients with metastatic clear-cell renal cancer with disease progression following 1 or 2 prior therapies (including one ICI) to receive tivozanib, a selective VEGFR TKI, either alone or in combination with nivolumab, a PD-1 inhibitor. During a median follow-up of 12 months, the primary endpoint of progression-free survival (PFS) determined by independent radiology review was not significantly different between treatment arms (median PFS, 7.4 months for tivozanib alone vs. 5.7 months for tivozanib/nivolumab). Treatment-emergent adverse events and serious adverse events occurred at similar rates in both treatment arms.