Tivozanib Maintains Long-Term PFS Benefit Over Sorafenib in Relapsed/Refractory RCC


Tivozanib continued to display a progression­-free survival benefit and rates vs sorafenib in patients with relapsed/refractory renal cell carcinoma who received 2 or 3 prior systemic regimens.

Michael B. Atkins, MD

Michael B. Atkins, MD

Tivozanib (Fotivda) continued to display a progression­-free survival (PFS) benefit and rates vs sorafenib (Nexavar) in patients with relapsed/refractory renal cell carcinoma (RCC) who received 2 or 3 prior systemic regimens, according to data from an exploratory analysis of the phase 3 TIVO-3 trial (NCT02627963) presented at the 2022 International Kidney Cancer Symposium.1

At a data cutoff of May 24, 2021, the investigator-assessed landmark PFS favored tivozanib over sorafenib (HR, 0.624; 95% CI, 0.49-0.79). Those data were comparable to the landmark PFS benefit reported by an independent review committee assessment at the original October 2018 data cutoff (HR, 0.672; 95% CI, 0.52-0.87).

Specifically, patients treated with tivozanib (n = 175) achieved an investigator-assessed, 36-month PFS rate of 12.3%, compared with 2.4% for patients treated with sorafenib (n = 175). The 48-month PFS rate was 7.6% for patients treated with tivozanib vs 0% for those given sorafenib.

“A clinically relevant proportion of patients were alive and progression free at 3 and 4 years after initiating tivozanib therapy compared with sorafenib, and this difference was consistent across all clinical and demographic subgroups evaluated,” lead study author Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, and colleagues, wrote in the poster presentation.

In March 2021, the FDA approved tivozanib for patients with relapsed/refractory advanced RCC following 2 or more prior systemic therapies.2 The regulatory decision was based on previously reported findings from the TIVO-3 trial.

At the 2022 International Kidney Cancer Symposium, investigators presented an exploratory analysis of investigator-assessed PFS and overall survival (OS) for the intent-to-treat population and prespecified subgroups.

TIVO-3 enrolled patients with advanced clear-cell metastatic RCC who progressed on 2 or 3 prior systemic therapies, including at least 1 VEGF TKI. Patients were stratified based on the prior regimen they were treated with and their IMDC prognostic score. They were randomly assigned 1:1 to receive 1.34 mg of oral tivozanib once daily for 3 weeks on, 1 week off per cycle or 400 mg of oral sorafenib twice daily continuously in a 4-week cycle.

Baseline characteristics between patients treated with tivozanib and those treated with sorafenib were similar, including IMDC risk, prior treatment, prior lines of treatment, age, sex, and geographic region.

Additional data showed that subgroups with at least a 15% increase in investigator-assessed PFS rate at 3 years included IMDC favorable risk (17.1% and 0% for tivozanib and sorafenib, respectively), female (17.5% and not evaluable [NE]), ECOG performance status of 0 (16.0% and 3.2%), at least 65 years of age (15.3% and NE), and geographic region of North America (16.5% and NE).

Moreover, the mature OS data revealed a nonsignificant trend favoring tivozanib continued to emerge with longer follow up data (HR, 0.89; 95% CI, 0.70-1.14).

“The rates of investigator-assessed, long-term PFS were higher with tivozanib compared with sorafenib at every time point evaluated. The odds of experiencing long-term PFS at 36 months with tivozanib were over 5 times higher than with sorafenib,” Atkins concluded.


  1. Atkins MB, Verzoni E, Escudier BJ, et al. Long-term PFS from TIVO-3: tivozanib (TIVO) vs sorafenib (SOR) in relapsed/refractory (R/R) advanced RCC. Abstract 33. Presented at: 2022 International Kidney Cancer Symposium; November 4-5, 2022. Accessed November 4, 2022.
  2. FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma. News release. FDA. March 10, 2021. Accessed November 4, 2022.
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