SAN FRANCISCO – The risk-benefit profile of the novel vascular endothelial growth factor (VEGF) inhibitor tivozanib when used as later-line therapy for renal cell carcinoma (RCC) appears to be similar to when it is used earlier, according to eagerly awaited results of the TIVO-3 trial.
Tivozanib, an oral tyrosine kinase inhibitor of the VEGF family of receptors with a long half-life, is designed both to optimize receptor blockade and minimize off-target toxicities, lead investigator, said at the the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
Positive progression-free survival results of the TIVO-1 trial () led to approval of this agent as first-line therapy for RCC in Europe. However, the Food and Drug Administration rejected approval because of a trend toward poorer overall survival, which was likely related to imbalanced cross-over to active treatment.
The TIVO-3 trial enrolled 350 patients with advanced clear-cell RCC who had experienced failure of two or three prior regimens, including a VEGF receptor tyrosine kinase inhibitor. They were randomized evenly to open-label tivozanib (1.5 mg q.d., 3 weeks on and 1 week off) or sorafenib (Nexavar) (400 mg b.i.d. continuously).
Main results showed that progression-free survival was about 2 months longer with tivozanib, compared with sorafenib. The difference translated to a 27% reduction in risk of events, reported Dr. Rini, professor of medicine at Case Western Reserve University, Cleveland, and leader of the genitourinary oncology program at the Cleveland Clinic.
The benefit was similar for most subgroups. The tivozanib group had a higher incidence of hypertension, but lower incidences of diarrhea, hand-foot syndrome, and rash.
“Tivozanib significantly improved progression-free survival and objective response rate compared to sorafenib in patients with treatment-refractory advanced RCC. It was superior in the subset of patients previously treated with checkpoint inhibitors, as well as the subset who had had two prior TKIs,” Dr. Rini said. “Responses to tivozanib, perhaps most impressively, were more durable than those with sorafenib. Tivozanib was very well tolerated, with on-target hypertension as the most common adverse event, but lower rates of off-target toxicities.”
Overall survival data at present show a trend toward shorter survival with tivozanib, but are not yet mature. Definitive results are expected later this year.