The efficacy of VEGF-targeting therapies in clinical trials led to their 
recommendation in clinical guidelines for use across the advanced or metastatic 
renal cell carcinoma (RCC) treatment landscape, however, tolerability (including 
off-target effects) has remained a challenge. Tivozanib is a selective inhibitor 
of all three VEGFRs, with limited off-target interaction, which demonstrates 
efficacy with improved tolerability relative to multikinase VEGFR-TKIs. Areas 
covered: Covered here is the clinical development of tivozanib in advanced RCC, 
including the pivotal Phase III, multicenter, open-label, randomized clinical 
study comparing tivozanib with sorafenib for the treatment of VEGF- and mTOR 
therapy-naïve advanced RCC patients. Also covered are ongoing trials, exploring 
the efficacy and safety of tivozanib in the setting of refractory disease and 
the utility of tivozanib in combination with checkpoint inhibitors for advanced 
RCC. Combination of a VEGFR-TKI and immunotherapy is promising in advanced RCC, 
if the treatment regimens have acceptable tolerability. Here the selectivity of 
tivozanib may contribute to an acceptable tolerability profile when used in 
combination therapy. Expert commentary: The approval of tivozanib provides an 
additional option for the first-line treatment of advanced or metastatic RCC 
patients in Europe and allows use of a VEGFR-TKI with selectivity for VEGFRs in 
this setting.