Tivozanib Shows Positive Results for Treatment of Advanced Renal Cell Carcinoma

Tivozanib (Fotivda) improved progression-free survival and reduced risk of death in patients with highly refractory advanced or metastatic disease.

AVEO Oncology’s investigational treatment for renal cell carcinoma (RCC) improved progression-free survival (PFS) and reduced risk of death in patients with highly refractory advanced or metastatic disease, according to recent data from a phase 3 clinical study.

Tivozanib (Fotivda) is an oral, once-daily vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) designed to optimize VEGF blockade while minimizing off-target toxicities, according to AVEO. It is currently approved for adult patients with advanced RCC in the European Union and is being investigated in several tumor types, including hepatocellular, colorectal, and breast cancers.

The TIVO-3 trial evaluated tivozanib (Fotivda) compared with sorafenib in 351 patients with RCC who have failed at least 2 prior regimens, with the primary endpoint of demonstrating a statistically significant benefit in PFS. Of the patients included in the trial, approximately 26% received checkpoint inhibitor therapy in previous lines of treatment.

According to the data, tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=.74, p=0.02). Patients treated with tivozanib experienced a median PFS of 5.6 months compared with 3.9 months for sorafenib. The study also showed that median PFS for tivozanib was longer among patients who received prior checkpoint inhibitor therapy and those who did not.

At the time of the final PFS analysis, data on the secondary endpoint of overall survival (OS) were not mature, with only 46% of potential OS events having been reported, according to AVEO. At preliminary analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The data showed that overall response rate was 18% for patients treated with tivozanib compared with 8% for patients who received sorafenib (p-0.02).

The most common adverse effect reported in patients in the trial was hypertension. Grade 3 or higher adverse events reported in the trial, which included thrombotic events, were consistent with those observed in previous tivozanib trials.

“Tivozanib’s therapeutic profile is distinct among VEGF TKIs as a treatment for RCC, with the TIVO-3 trial demonstrating a significant PFS benefit and a favorable tolerability profile,” principal investigator Brian Rini, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and director of Cleveland Clinic Genitourinary Cancer Program, said in a statement.

According to Dr Rini, the findings suggest the need to study tivozanib further in combination with immunotherapy.

AVEO plans to submit a new drug application to the FDA in approximately 6 months based on the results from the TIVO-3 trial and the previously completed phase 3 TIVO-1 trial, according to the release.


AVEO Oncology Announces Phase 3 TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma Meets Primary Endpoint [news release]. AVEO Oncology’s website. https://www.aveooncology.com/wp-content/uploads/2018/11/AVEO-TIVO-3-Topline.pdf. Accessed November 6, 2018.