TIVO-1 Crossover: Tivozanib Active for Advanced RCC

The vascular endothelial growth factor receptor (VEGFR) inhibitor tivozanib had potent antitumor activity among patients with advanced renal cell carcinoma (RCC), according to the results of an open-label, crossover analysis of patients from the phase III global multicenter TIVO-1 clinical trial.

The TIVO-1 trial showed that tivozanib significantly improved progression-free survival (PFS) and overall survival (OS) compared with sorafenib. In addition, patients randomized to treatment with tivozanib had significantly higher overall response rates (ORRs) than those with sorafenib. However, due to a lack of available second-line therapies in Eastern Europe, many patients who progressed on sorafenib were later treated with tivozanib.

“The results of overall survival in TIVO-1 were likely confounded by the differential use of subsequent cancer therapy in the two treatment arms, as well as the activity of tivozanib in second line,” study researcher Ana M. Molina, MD, of Weill Cornell Medicine, and colleagues wrote in the European Journal of Cancer.

Therefore, this crossover analysis was conducted to evaluate outcomes in patients in TIVO-1 who progressed on sorafenib and were later treated with tivozanib.

In the open-label extension study, 277 patients were recruited from the three reporting groups of TIVO-1, and 161 of these patients were included in the current analysis. Tivozanib was administered at a 1.5-mg dose daily for 3 weeks on and 1 week off. Crossover patients were exposed to tivozanib for a median of 8 cycles.

From the beginning of tivozanib treatment, median PFS was 11.0 months and median OS was 21.6 months. Partial response was the best overall response, and more than half of patients were able to achieve stable disease. The median duration of response was 15.2 months for patients with partial response and 12.7 months for those with stable disease.

“Overall, data from this crossover study of patients with advanced RCC demonstrated the antitumor activity of tivozanib, with a median progression-free survival of 11 months and a median overall survival of 22 months after progressive disease with sorafenib treatment on TIVO-1,” the researchers wrote.

According to the researchers, tivozanib “had a favorable safety profile compared with other VEGFR TKIs, with a low incidence of class-related adverse events, including diarrhea, asthenia, and palmar-plantar erythrodysesthesia syndrome.”

The majority of patients experienced some kind of adverse events; the most common were hypertension, diarrhea, and fatigue. Treatment-related adverse events of grade 3 or worse occurred in about 25% of patients. Dose reductions or interruptions were necessary in 9% and 16% of patients, respectively.

“Current research is focused on combinations of active agents in first and subsequent lines of therapy. Overlapping toxicities are likely to limit the number of combinations that are feasible,” the researchers wrote. “Tivozanib, with its very favorable adverse events profile, is an ideal candidate for studies in combination.”