The FDA approved the angiogenesis inhibitor tivozanib (Fotivda) for relapsed/refractory advanced renal cell carcinoma (RCC).
Tivozanib is now the first approved therapy for patients who received two or more prior lines of therapy for advanced RCC. Support for the approval came primarily from the randomized TIVO-3 trial that showed tivozanib improved progression-free survival (PFS) as compared with sorafenib (Nexavar), another angiogenesis inhibitor.
It is the first treatment to improve PFS after two or three prior lines of therapy.
The TIVO-3 trial involved 350 patients who had received two or three prior lines of therapy for relapsed/refractory advanced RCC. Investigators in 12 countries randomized the patients to the two antiangiogenic agents, and treatment continued until disease progression or development of unacceptable toxicity.
The primary endpoint was PFS, and data analysis showed a median PFS of 5.6 months with tivozanib versus 3.9 months with sorafenib. The difference represented a 27% reduction in the hazard for disease progression or death with tivozanib (95% CI 0.56-0.75, P=0.016). Median overall survival did not differ significantly between treatment groups, but was numerically higher with sorafenib (19.2 vs 16.4 months, HR 0.97, 95% CI 0.75-1.24). Objective response rates were 18% with tivozanib and 8% with sorafenib.
Dr Rajeentheran Suntheralingam
Consultant Urologist / Urological Surgeon
For more info, see the following link:
FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma
On March 10, 2021, the Food and Drug Administration approved tivozanib (Fotivda, AVEO Pharmaceuticals, Inc.), a kinase inhibitor, for adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.
Efficacy was evaluated in TIVO-3 (NCT02627963), a randomized (1:1), open-label, multicenter trial of tivozanib versus sorafenib in patients with relapsed or refractory advanced RCC who received two or three prior systemic treatments,including at least one VEGFR kinase inhibitor other than sorafenib or tivozanib. Patients were randomized to either tivozanib 1.34 mg orally once daily for 21 consecutive days every 28 days or sorafenib 400 mg orally twice a day continuously, until disease progression or unacceptable toxicity.
The main efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee. Other efficacy endpoints were overall survival (OS) and objective response rate (ORR).
Median PFS was 5.6 months (95% CI: 4.8, 7.3) in the tivozanib arm (n=175) compared with 3.9 months (95% CI: 3.7, 5.6) for those treated with sorafenib (HR 0.73; 95% CI: 0.56, 0.95; p=0.016). Median OS 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 ORR was 18% (95% CI: 12%, 24%) for the tivozanib arm and 8% (95% CI: 4%, 13%) for the sorafenib arm.
The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most common grade 3 or 4 laboratory abnormalities (≥5%) 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.
View full prescribing information for Fotivda.
The FDA approved this application 3 weeks ahead of the FDA goal date.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
Dr Rajeentheran Suntheralingam
Consultant Urologist / Urological Surgeon
