Tivozanib extended PFS compared with sorafenib among patients with highly refractory advanced or metastatic renal cell carcinoma, according to randomized phase 3 study results released by the agent’s manufacturer.
Tivozanib (Fotivda, AVEO Oncology) is an oral, once-daily, vascular endothelial growth factor tyrosine kinase inhibitor. It is approved in the European Union, Norway and Iceland for treatment of adults with advanced renal cell carcinoma.
The multicenter, open-label TIVO-3 trial included 351 patients with advanced or metastatic renal cell carcinoma who failed at least two prior therapies, including a vascular EGFR TKI. Approximately one-quarter (26%) received checkpoint inhibitor therapy.
Researchers randomly assigned patients 1:1 to tivozanib or sorafenib. The trial design did not allow for crossover.
The trial met its primary endpoint of PFS, showing a 44% improvement in median PFS with tivozanib (5.6 months vs. 3.9 months; HR = 0.74; P = .02). Researchers observed the PFS benefit among all patients regardless of prior checkpoint inhibitor therapy.
Secondary endpoints included OS, overall response rate, and safety and tolerability.
OS data are not yet mature; however, at the time of the preliminary OS analysis, results showed no statistically significant difference between treatment groups.
The final survival analysis is planned for August 2019.
Researchers reported a higher ORR in the tivozanib group (18% vs. 8%; P = .02).
Tivozanib appeared well tolerated. Incidence of grade 3 or higher adverse events were consistent with those observed in previous trials.
The most common adverse event among tivozanib-treated patients was hypertension.
Complete results of the trial will be submitted for presentation at an upcoming medical meeting.
“Tivozanib’s therapeutic profile is distinct among VEGF TKIs as a treatment for renal cell carcinoma, with the TIVO-3 trial demonstrating a significant PFS benefit and a favorable tolerability profile,” Brian I. Rini, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, director of Cleveland Clinic’s genitourinary cancer program, and principal investigator of the TIVO-3 trial, said in an AVEO Oncology-issued press release.
“In the advanced disease setting, these outcomes are particularly meaningful, providing the first large, pivotal data set that shows sequencing of treatment following earlier TKI and immunotherapy treatment,” Rini added. “This profile suggests an important place for tivozanib in the evolving treatment paradigm for renal cell carcinoma and, taken together with early combination data, the need to study tivozanib further in combination with immunotherapies.”