Background: Tivozanib (TIVO) is a potent and selective VEGF receptor (R) tyrosine kinase inhibitor with a long half-life designed to optimize the VEGF blockade while minimizing off-target toxicities. The TIVO-3 trial demonstrated improved progression-free survival (PFS) when compared to sorafenib (SOR; 5.6 mo. vs 3.9 mo., respectively) with a hazard ratio (HR) of 0.73. TIVO showed better tolerability with reduced need for dose interruptions (p = 0.0164) and dose reductions (p = 0.0147) as compared to SOR. Methods: Data was analyzed to identify relationships between and age or prior use of immune checkpoint inhibitors (CPI). Results: Of the 343 patients treated on study, 120 (35%) were between age 65 and 75 and 34 (10%) were over 75. Adverse events were less frequent for TIVO compared to SOR in all age groups and drug exposure was consistently greater in the TIVO arm. Of particular interest, the tolerability advantages noted in the total population are also observed in the patients 75 and over with almost half the rate of the adverse drug reactions leading to dose reduction or discontinuation compared to SOR. Patients treated with prior CPI had an increased need for dose adjustment, but dose adjustments were less common with TIVO than SOR in CPI exposed and naïve patients. Conclusions: Tivozanib was better tolerated than sorafenib regardless of age or prior CPI treatment. Dose adjustments and interruptions are more common after prior CPI. Clinical trial information: NCT02627963