Tivozanib (VEGFR TKI) Beats Tivozanib+nivolumab in post-ICI mRCC, extending 2L PFS

Tivozanib is an oral VEGFR-1/2/3 tyrosine kinase inhibitor (TKI); TiNivo-2 randomized post–immune checkpoint inhibitor (ICI) metastatic RCC patients to standard-dose tivozanib 1.34mg (21/28 days) vs reduced-dose tivozanib 0.89mg plus nivolumab 480mg q4w (n=343 randomized; 171 vs 168 treated) with final data cutoff October 17, 2025 (median follow-up 28.4 vs 27.2 months). In the 2L subgroup, median PFS favored tivozanib monotherapy (9.23 months [7.29–11.04] vs 5.95 months [5.42–7.95]), with the abstract also stating a continued OS advantage for tivozanib across subgroups; safety remained consistent, led by grade ≥3 hypertension (22.8% vs 22.6%), with grade ≥3 diarrhea (2.3% vs 3.6%) and palmar-plantar erythrodysaesthesia (0.6% vs 1.2%) and treatment-related SAEs in 8.8% vs 10.7%. For real-world context in this post-ICI slot, VEGFR-TKI monotherapy benchmarks are typically ORR ~22%–41% and median PFS ~6–13 months (cabozantinib often landing around ~10–11 months in select datasets), so the ~9.2-month 2L PFS with tivozanib looks broadly “in-family” for active TKIs—while the key differentiator here is that PD-1 “rechallenge” with nivolumab did not help (NCT04987203).