Tivozanib, vascular endothelial growth factor receptor inhibitor, met the primary endpoint of improved progression free survival compared to sorafenib in the phase 3 TIVO-3 study in patients with previously treated metastatic renal cell carcinoma. In this study we sought to understand the temporal characteristics of treatment related adverse events (TRAEs) and frequency and timing of the dose modifications.
In this open label, randomized, phase 3 TIVO-3 study, previously treated patients with a diagnosis of metastatic renal cell carcinoma and with measurable disease were included. Patients were randomized to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily continuously. Based on updated safety analysis data (cutoff date of August 15, 2019), time to onset of the most commonly reported TRAEs, duration of toxicity, rate of dose modifications was calculated for each treatment arm.
Overall, 350 patients were randomly assigned to receive tivozanib or sorafenib;173 patients from the tivozanib arm and 170 patients from the sorafenib arm were included in this analysis. Patients received a median of 11.9 cycles (336 days) and 6.7 cycles (192 days) of tivozanib and sorafenib, respectively. Dose reductions, interruptions and treatment discontinuations were 25%, 50%, and 21%, and 39%, 50%, and 30% in the tivozanib and sorafenib arms, respectively, with a longer time to onset of TRAEs in the tivozanib arm.
Tivozanib was associated with less TRAEs, fewer dose modifications, a longer time to onset and a shorter duration of TRAEs compared to sorafenib.
Clinical genitourinary cancer. 2022 Aug 23 [Epub ahead of print]
Zeynep B Zengin, Sumanta K Pal, David F McDermott, Bernard Escudier, Thomas E Hutson, Camillo Porta, Elena Verzoni, Michael B Atkins, Vijay Kasturi, Brian Rini
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA., Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA., Institut Gustave Roussy, Villejuif, France., Baylor Sammons Cancer Center-Texas Oncology, Dallas, TX., Division of Medical Oncology, Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Bari, Italy., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Georgetown Lombardi Comprehensive Cancer Center, Washington, DC., Aveo Oncology, Boston, MA., Vanderbilt-Ingram Cancer Center, Nashville, TN. Electronic address: .