FDA approves tivozanib for kidney cancer


The FDA has approved tivozanib (Fotivda) for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) who have received 2 or more prior systemic therapies.1

The approval is based on data from the phase 3 TIVO-3 trial. Results from the study presented during the 2020 ASCO Virtual Scientific Program2 showed that the VEGF-TKI tivozanib demonstrated a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with highly relapsed/refractory metastatic RCC.

Results showed that the final hazard ratio (HR) for OS was 0.97 (P = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib and 19.2 months for sorafenib. A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.

Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; P = .016).

Dr. Brian Rini, chief of clinical trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial

Brian Rini, MD

“Today’s approval of Fotivda provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to two or more prior systemic therapies,” Brian Rini, MD, chief of clinical trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial, stated in a press release.

“With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated treatment options in the relapsed or refractory setting. The TIVO-3 study is the first positive phase 3 study in RCC patients who received two or more prior systemic therapies, and also the first phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape,” added Rini.

In the multicenter, open-label, randomized TIVO-3 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.

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.

A subanalysis of the TIVO-3 trial3 presented during the 2021 Genitourinary Cancers symposium showed that tivozanib significantly increased quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) versus sorafenib when used in the third- or fourth-line setting for patients with metastatic RCC.

Aveo, the manufacturer of tivozanib, reported in the press release that the VEGF-TKI will be made available to US patients by the end of March.


1. AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. Published online March 10, 2021. Accessed March 10, 2021. https://bwnews.pr/3vbdRY4.

2. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.

3. 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

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