On March 10, the U.S. Food and Drug Administration (FDA) approved tivozanib (Fotivda), a kinase inhibitor, for adult patients with relapsed or refractory advanced renal cell carcinoma following two or more prior systemic therapies.
Efficacy was evaluated in TIVO-3 (ClinicalTrials.gov identifier NCT02627963), a randomized, open-label, multicenter trial of tivozanib vs sorafenib in patients with relapsed or refractory advanced renal cell carcinoma who had received two or three prior systemic treatments, including at least one VEGFR kinase inhibitor other than sorafenib or tivozanib. Patients were randomly assigned to receive either tivozanib at 1.34 mg orally once daily for 21 consecutive days every 28 days or sorafenib at 400 mg orally twice a day continuously, until disease progression or unacceptable toxicity.
The main efficacy outcome measure was progression-free survival, assessed by a blinded independent radiology review committee. Other efficacy endpoints were overall survival and objective response rate.
Median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.8–7.3) in the tivozanib arm compared with 3.9 months (95% CI = 3.7–5.6) for those treated with sorafenib (hazard ratio [HR] = 0.73, 95% CI = 0.56–0.95, P = .016). Median overall survival was 16.4 (95% CI = 13.4–21.9) and 19.2 months (95% CI = 14.9–24.2), for the tivozanib and sorafenib arms, respectively (HR = 0.97, 95% CI = 0.75–1.24). The objective response rate was 18% (95% CI = 12%–24%) for the tivozanib arm and 8% (95% CI = 4%–13%) for the sorafenib arm.
The most commonly reported adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most commonly reported grade 3 or 4 laboratory abnormalities were decreased sodium, increased lipase, and decreased phosphate.
The recommended tivozanib dose is 1.34 mg once daily (with or without food) for 21 consecutive days every 28 days until disease progression or unacceptable toxicity.