As reported in The Lancet Oncology by Brian I. Rini, MD, and colleagues, the phase III TIVO-3 trial has shown a statistically significant increase in progression-free survival with tivozanib vs sorafenib as a third- or fourth-line treatment for advanced renal cell carcinoma.
The open-label trial included 350 patients with metastatic disease from 120 sites in 12 countries. Patients were randomly assigned between May 2016 and August 2017 to receive third- or fourth-
Brian I. Rini, MD
line treatment with oral tivozanib at 1.5 mg once daily for 21 days on and 7 days off in 28-day cycles (n = 175) or continuous oral sorafenib at 400 mg twice daily (n = 175) until disease progression or unacceptable toxicity. Patients could not have received prior tivozanib or sorafenib and had to have received at least one prior VEGFR inhibitor.
The primary endpoint was progression-free survival on independent review committee assessment in the intention-to-treat population.
Median follow-up was 19.0 months. Median progression-free survival was 5.6 months (95% confidence interval [CI] = 5.29–7.33 months) in the tivozanib group vs 3.9 months (95% CI = 3.71–5.55 months) in the sorafenib group (hazard ratio [HR] = 0.73, P = .016). Progression-free survival was 28% vs 11% at 1 year and 18% vs 5% at 2 years. Among the 26% of patients with prior immune checkpoint inhibitor therapy (a stratification factor), median progression-free survival was 7.3 months vs 5.1 months (HR = 0.55, 95% CI = 0.32–0.94). Median overall survival was 16.4 months vs 19.7 months (HR = 0.99, P = .95).
The most common grade 3 or 4 treatment-related adverse event was hypertension, which occurred in 20% of the tivozanib group and 14% of the sorafenib group. Serious treatment-related adverse events occurred in 11% vs 10% of patients, with the most common in both groups being gastrointestinal events. Adverse events led to dose interruption in 48% vs 63% of patients and to dose reduction in 24% vs 38%. No treatment-related deaths were observed.
The investigators concluded, “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.” ■