The Food and Drug Administration (FDA) has approved Fotivda® (tivozanib; AVEO Oncology) for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) after 2 or more prior systemic therapies.

Fotivda is an oral, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor. The approval was based on data from the multicenter, randomized, open-label phase 3 TIVO-3 study (ClinicalTrials.gov: NCT02627963) that compared tivozanib to sorafenib in 350 patients 18 years of age and older with relapsed or refractory advanced RCC who received 2 or 3 prior systemic treatments including at least 1 VEGFR kinase inhibitor other than sorafenib or tivozanib.

Patients were randomly assigned 1:1 to receive either tivozanib 1.34mg orally once daily for 21 days followed by 7 days off treatment for a 28-day cycle, or sorafenib 400mg orally twice daily continuously, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR).

Median PFS was observed to be significantly longer among patients treated with tivozanib compared with sorafenib (5.6 months [95% CI, 4.8-7.3] vs 3.9 months [95% CI, 3.7-5.6]; hazard ratio [HR] 0.73; [95% CI, 0.56-0.95]; =.016). Median OS was 16.4 months (95% CI, 13.4-21.9) for tivozanib and 19.2 months (95% CI, 14.9-24.2) for sorafenib (HR 0.97; 95% CI, 0.75-1.24). Results also showed an ORR of 18% (95% CI, 12-24) with tivozanib compared with 8% (95% CI, 4-13) for sorafenib.


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As for safety, the most common adverse reactions (incidence of greater than or equal to 20%) were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most common grade 3 or 4 laboratory abnormalities (incidence of greater than or equal to 5%) were decreased sodium, increased lipase, and decreased phosphate.

“The TIVO-3 study is the first positive phase 3 study in RCC patients who received 2 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,” said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. “With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”

Fotivda is expected to be available by March 31, 2021. The product will be supplied as 0.89mg and 1.34mg of tivozanib in 21-count bottles.

References

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. [press release]. Boston, MA: AVEO Oncology; March 10, 2021. 

2.    Fotivda® [package insert]. Boston, MA: AVEO Pharmaceuticals, Inc.; 2021.