Latest tivozanib data shared as FDA weighs kidney cancer approval


The FDA is scheduled to decide on a new drug application for tivozanib by March 31, 2021, for use in relapsed/refractory renal cell carcinoma.

A subanalysis of the phase 3 TIVO-3 trial presented during the 2021 Genitourinary Cancers symposium showed that tivozanib hydrochloride (Fotivda) significantly increased quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) versus sorafenib (Nexavar) when used in the third- or fourth-line setting for patients with metastatic renal cell carcinoma (RCC).1

Based on previously reported data from the TIVO-3 study, the FDA accepted a new drug application (NDA) for the use of the VEGF tyrosine kinase inhibitor tivozanib in patients with relapsed/refractory RCC. The agency is scheduled to decide on the NDA on or before March 31, 2021.

“The difference in Q-TWiST in TIVO-3 was primarily driven by benefits of tivozanib in TWiST, partially offset by superiority of sorafenib in time after progression or relapse [REL],” the investigators wrote in their abstract for the 2021 American Society of Clinical Oncology (ASCO) Genitourinary Cancer Symposium.

To quantify the net health benefits of tivozanib, the investigators applied Q-TWiST methods because of the similar survival of the 2 agents reported previously.2

Investigators calculated mean Q-TWiST by applying utility coefficients of 0.5, 1.0, and 0.5 to the 36-month restricted mean health states of time with toxicity, time without symptoms and toxicity, and REL, respectively.1 The relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the sorafenib mean overall survival (OS).

The mean Q-TWiST was 15.04 months for tivozanib versus 12.78 months for sorafenib (P =.0493). The relative gain for tivozanib was 11.2%. With more follow-up, there were better Q-TWiST means. Q-TWiST at 36 months of follow-up, which was the primary end point of this analysis, the mean was 2.25 (95% CI, 0.01-4.51) in favor of tivozanib. Mean TWiST was significantly longer for tivozanib versus sorafenib (10.30 months vs 5.35 months; TABLE).

For this multicenter, randomized, controlled, open-label trial, 350 patients were split evenly between the 2 drugs and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk category and type of previous therapy.2 These patients had to progress on 2 or 3 prior systemic regimens, at least 1 of which had to be a VEGFR tyrosine kinase inhibitor other than sorafenib or tivozanib.

Patients either received 1.5 mg of tivozanib mg orally once a day on 4-week cycles or sorafenib at 400 mg orally twice a day continuously. The primary end point was progression-free survival (PFS) by independent review in the intention-to-treat population.

In the previous report of TIVO-3, tivozanib increased PFS compared with sorafenib but did not show a difference in OS. The PFS difference at a 19-month median follow-up was significant between tivozanib and sorafenib at 5.6 and 3.9 months, respectively (HR, 0.73; 95% CI, 0.56-0.94; P =.016).

The most common grade 3/4 treatment-related adverse events (TRAEs) in the originally published data were hypertension in 20% of patients receiving tivozanib and 14% of patients receiving sorafenib. Serious TRAEs were observed in 11% versus 10% of patients respectively, but no treatment-related deaths were reported.

“As a third- or fourth-line treatment for RCC, tivozanib significantly increased Q-TWiST relative to sorafenib, primarily through an increase in TWiST, which is generally considered to be the state with highest utility to patients. Consequently, Q-TWiST may be considered an alternative patient-centered measure of benefit of tivozanib in these settings,” the investigators wrote in their conclusion.1


1. Szarek M, Needle MN, Rini BI, et al. Q-TWiST analysis of tivozanib (T) versus sorafenib (S) in patients with advanced renal cell carcinoma (RCC) in the TIVO-3 study. J Clin Oncol. 2021;39(suppl 6):298. doi:10.1200/JCO.2021.39.6_suppl.298

2. 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(1):95-104. doi: 10.1016/S1470-2045(19)30735-1

Related Videos
Dr. Jasmeet Kaur in an interview with Urology Times
Dr. Martin Voss in an interview with Urology Times
Dr. Jacqueline Brown in an interview with Urology Times
blurred clinic hallway
Dr. Dalia Kaakour in an interview with red Urology Times backdrop
Dr. Maria Teresa Bourlon in an interview with Urology Times
Dr. David Braun in an interview with Urology Times
Dr. Neeraj Agarwal in an interview with Urology Times
Dr. Saby George in an interview with Urology Times
Dr. Laura Bukavina in an interview with Urology Times
Related Content
© 2024 MJH Life Sciences

All rights reserved.