Dr McGregor on the Outcomes of an Analysis Evaluating the Optimal Dose of Tivozanib in RCC

“Hypertension didn’t seem to change the pharmacokinetics of tivozanib, and…hypertension risks were no different between [tivozanib] at 0.89 mg or 1.34 mg.”

Bradley McGregor, MD, the director of Clinical Research for the Lank Center of Genitourinary Oncology, a senior physician, and the Marra Lochiatto Investigator at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, highlighted the outcomes of an exposure response analysis of tivozanib (Fotivda) for the treatment of patients with renal cell carcinoma (RCC).

A notable finding based on the exposure response analysis was that the incidence of hypertension did not affect the pharmacokinetics among patients treated with tivozanib, McGregor began. He explained that the risk of hypertension also did not differ between tivozanib at 0.89 mg and 1.34 mg, which emphasized that tivozanib at 1.34 mg may show superiority over the 0.89-mg dose, especially in the clinic and with FDA indications.

The analysis explored the association between tivozanib and exposure with progression-free survival, tumor size, and hypertension. Exploratory analysis data from TIVO-1 (NCT01030783), TIVO-3 (NCT02627963), and TiNivo-2 (NCT04987203) trials were used to distinguish these associations. Regarding any grade hypertension, the incidence was 0.413 (95% CI, 0.383-0.444) with tivozanib at 1.34 mg compared with an incidence of 0.388 (95% CI, 0.358-0.419) at 0.89 mg. The incidence of grade 3 or greater hypertension with tivozanib at 1.34 mg vs 0.89 mg, respectively, was 0.238 (95% CI, 0.213-0.265) and 0.215 (95% CI, 0.191-0.242).

Based on the outcomes of the analysis, establishing the optimal dose of tivozanib has helped with ongoing trials, McGregor said. This included the phase 3 STRIKE trial (NCT06661720), which is evaluating the addition of tivozanib to standard therapy of pembrolizumab (Keytruda) in patients with high risk RCC to identify areas of improving outcomes, he noted. Pembrolizumab currently improves recurrence-free survival without any significant effects on quality of life, he added. As the STRIKE trial was being designed, the dose of tivozanib at 1.34 mg on days 1 through 21 of a 28-day cycle for 6 months, plus pembrolizumab for 1 year, was determined as the most feasible for patients in the intervention group, McGregor concluded.