FDA Approval Summary: Tivozanib for Relapsed or Refractory Renal Cell Carcinoma

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Advanced renal cell carcinoma (RCC) presents a significant challenge in treatment, particularly for patients with relapsed or refractory disease.
• Limited effective systemic therapies exist for patients who have undergone multiple prior treatments.

Purpose of the Study:

• To evaluate the efficacy and safety of tivozanib compared to sorafenib in patients with relapsed or refractory advanced RCC.
• To assess progression-free survival (PFS) as the primary endpoint in this patient population.

Main Methods:

• The TIVO-3 study was a randomized trial comparing tivozanib (1.34 mg daily) to sorafenib (400 mg twice daily) in patients with relapsed/refractory advanced RCC.
• Patients received treatment for 21 days of every 28-day cycle or continuously.
• Progression-free survival (PFS) was assessed using RECIST v1.1 criteria.

Main Results:

• Tivozanib demonstrated a statistically significant improvement in PFS compared to sorafenib (HR, 0.73; P=0.016), with median PFS of 5.6 months vs. 3.9 months.
• Overall survival (OS) showed no detrimental effect with tivozanib (HR, 0.97).
• Hypertension was the most common severe adverse event (24%) with tivozanib, but rates of diarrhea, rash, and palmar-plantar erythrodysesthesia were lower than with sorafenib. Tivozanib also had lower rates of dose modification.

Conclusions:

• Tivozanib is an effective treatment option for patients with relapsed or refractory advanced RCC, offering improved PFS over sorafenib.
• Tivozanib presents a favorable safety profile with reduced incidence of certain common toxicities associated with VEGF inhibitors.
• The FDA approval of tivozanib provides a new therapeutic choice for patients with advanced RCC after failure of prior systemic therapies.