FDA Approves Tivozanib for Advanced Renal Cell Carcinoma

Renal cell carcinoma cells.

Tivozanib (Fotivda®, Aveo Pharmaceuticals, Inc.) has been approved by the FDA for adult patients with relapsed/refractory advanced renal cell carcinoma (RCC) who were previously treated with at least two systemic therapies.

“Treatment for RCC has been revolutionized by inhibitors of the vascular endothelial growth factor receptor (VEGFR),” wrote the investigators of TIVO-3 (NCT02627963), the trial on which the approval was based, led by Brian Rini, MD, Chief of Clinical Trials at the Vanderbilt-Ingram Cancer Center, and Sumanta Pal, Co-Director of the Kidney Cancer Program at City of Hope. “Previous studies have suggested that treatment with a VEGFR tyrosine kinase inhibitor (TKI) might be effective in patients who had previous checkpoint inhibitor therapy. Therefore, TIVO-3 was designed to compare the efficacy and safety of tivozanib, a potent and selective VEGFR inhibitor, with those of sorafenib as third-line or fourth-line therapy in patients with metastatic RCC.”

The randomized phase 3 trial enrolled 350 patients with relapsed or refractory advanced RCC who had received at least two prior systemic therapies, including at least one other VEGFR TKI. Patients were randomized in a 1:1 ratio to receive tivozanib 1.34 mg orally once daily for three weeks of each four-week cycle or sorafenib 400 mg orally twice daily continuously, until disease progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population, with secondary end points of overall survival and objective response rate.

At a median follow-up of 19 months, tivozanib produced a significantly greater median progression-free survival compared with sorafenib (5.6 vs 3.9 months). Median overall survival was 16.4 months in the tivozanib arm and 19.2 months in the sorafenib arm (hazard ratio 0.97). Patients receiving tivozanib experienced a higher objective response rate compared with those receiving sorafenib (18% vs 8%).

Adverse events occurring in at least 20% of patients treated with tivozanib included fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. Grade 3 or 4 laboratory abnormalities experienced by at least 5% of patients included decreased sodium, increased lipase, and decreased phosphate. Serious treatment-related adverse events occurred in 11% of patients receiving tivozanib and in 10% of those receiving sorafenib, with no treatment-related deaths in either arm.

“Our study showed that tivozanib as third-line or fourth-line therapy improved progression-free survival and was better tolerated compared with sorafenib in patients with metastatic renal cell carcinoma,” concluded Dr. Rini and colleagues in their January 2020 publication of the study’s results in Lancet Oncology.

The recommended dose of tivozanib is 1.34 mg once daily for 21 consecutive days every 28 days, with or without food, until disease progression or unacceptable toxicity.

For More Information

Rini BI, Pal SK, Escudier BJ, et al (2020). Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomized, controlled, open-label study. Lancet Oncol, 21(1):95-104. DOI:10.1016/S1470-2045(19)30735-1

Clinicaltrials.gov (2021). A study to compare tivozanib hydrochloride to sorafenib in subjects with refractory advanced RCC. NLM identifier: NCT02627963.

Fotivda® (tivozanib) prescribing information (2021). Aveo Pharmaceuticals, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212904s000lbl.pdf

US Food & Drug Administration (2021). FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma

Image credit: Nephron. Licensed under CC BY-SA 3.0

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