TIVO-3: Post-Hoc and Subgroup Analyses of Third- and Fourth-Line Tivozanib Treatment Compared with Sorafenib

Tivozanib is a tyrosine kinase inhibitor (TKI) that is selective for vascular endothelial growth factor receptors. In the phase 3 TIVO-3 trial, which enrolled patients with metastatic renal-cell carcinoma (RCC) who had received 2 or 3 lines of systemic therapy, tivozanib was shown to extend progression-free survival relative to sorafenib, with better tolerability.1 Based on the results of the TIVO-3 trial, tivozanib was approved for adults with relapsed or refractory RCC who have received ≥2 previous systemic therapies in March 2021.2

In the follow-up reports of TIVO-3, several analyses confirmed the benefit of tivozanib. In long-term follow-up, objective response rate was 23% with tivozanib and 11% with sorafenib.3 Furthermore, tivozanib improved progression-free survival versus sorafenib regardless of previous treatment, including in those patients who had previously received multiple TKIs.4 Despite longer treatment exposure, tivozanib was also shown to have a better tolerability profile than sorafenib—a benefit that extended across age ranges and with or without previous receipt of immunotherapy.5,6 The investigators of these studies concluded that tivozanib remains a durably efficacious and tolerable option for heavily pretreated patients with advanced RCC.3-6


  1. Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21:95-104.
  2. US Food and Drug Administration. FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma. Updated March 10, 2021. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma. Accessed November 18, 2021.
  3. Verzoni E, Escudier B, Hutson TE, et al. TIVO-3: durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2021;39(15_suppl):Abstract 4546.
  4. Rini BI, Pal SK, Escudier B, et al. TIVO-3: tivozanib in patients with advanced renal cell carcinoma (aRCC) who have progressed after treatment with axitinib. J Clin Oncol. 2021;39(suppl 6):Abstract 278.
  5. Escudier B, Rini BI, Pal SK, et al. TIVO-3: age-related tolerability outcomes of tivozanib versus sorafenib in metastatic relapsed or refractory renal cell carcinoma, a subgroup analysis of the TIVO-3 clinical trial. J Clin Oncol. 2021;39(15_suppl):Abstract e16553.
  6. Pal SK, McDermott DF, Escudier B, et al. Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the phase 3 TIVO-3 study of relapsed or refractory mRCC. J Clin Oncol. 2021;39(15_suppl):Abstract 4567.

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