Dr McGregor on the Rationale of Analyzing the Efficacy and Safety Exposure Response of Tivozanib in RCC

“In the past couple years, we’ve had 2 big trials that have really established that immunotherapy with a TKI…is no better than TKI [alone] when patients had progressed on immunotherapy.”

Bradley McGregor, MD, director of Clinical Research for the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute and assistant professor of Medicine at Harvard Medical School, discusses the rationale of analyzing the integrated efficacy and safety exposure response of tivozanib (Fotivda) for the treatment of patients with advanced renal cell carcinoma (RCC).

In recent years, phase 3 clinical trials have demonstrated that immunotherapy plus a TKI did not significantly improve outcomes vs a TKI alone in patients with advanced RCC who experienced disease progression on a checkpoint inhibitor–containing regimen, McGregor begins. Notably, the TiNivo-2 study (NCT04987203) specifically demonstrated worse outcomes in patients who were treated with tivozanib at 0.89 mg on days 1 to 21 in a 28-day cycle plus nivolumab (Opdivo) at 480 mg every 4 weeks due to the potential risk of higher rates of grade 3/4 hypertension, he explains.

The analysis also evaluated data from the phase 3 TIVO-1 (NCT01030783) and TIVO-3 (NCT02627963) trials, both of which assessed tivozanib at 1.34 mg vs sorafenib (Nexavar). In TIVO-1, patients were treated with tivozanib or sorafenib as initial targeted therapy, whereas patients in TIVO-3 were treated with tivozanib or sorafenib after progression on 2 or 3 systemic therapies.

Exposure response models from the analysis showed that tivozanib at 1.34 mg provided improved antitumor activity compared with tivozanib at 0.89 mg, and the incidence of hypertension was similar. Furthermore, the data suggested that tivozanib at 1.34 mg also provided a greater decrease in tumor size and may be more tolerable.

The optimal dose of tivozanib was considered in the analysis, along with what should be done during the treatment disease setting, McGregor notes. Based on the exposure response correlation, he concludes that the correct dosing has been established regarding efficacy and safety.