AVEO Oncology and Astellas Pharma Inc. have reported overall survival (OS) for tivozanib, an investigational agent, from the phase III TIVO-1 (TIvozanib Versus sOrafenib in 1st line advanced RCC) study in patients with advanced renal cell carcinoma (RCC). The final OS analysis, as specified by the protocol, shows a median OS of 28.8 months (95 per cent confidence interval [CI]: 22.5–NA) for tivozanib versus a median OS of 29.3 months (95 per cent CI: 29.3–NA) for the comparator arm, sorafenib.

No statistical difference between the two arms (HR=1.245, p=0.105) was observed. The OS data are included in the tivozanib New Drug Application (NDA) filing and will be presented at the 2013 American Society for Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) on February 16.

Overall survival is a secondary endpoint of the TIVO-1 study. A one-sided crossover for patients randomized to the sorafenib (comparator) arm was offered pursuant to a separate, long-term treatment protocol to allow trial participants to receive tivozanib upon disease progression. This resulted in a substantial difference in the use of subsequent therapies. Of the patients who discontinued their initial therapy, 10 per cent originally on the tivozanib arm received subsequent anti-VEGF therapy (36 per cent received any subsequent therapy) while 70 per cent of patients originally on the comparator arm received subsequent anti-VEGF therapy (74 per cent received any subsequent therapy).

“It's encouraging to see that patients in the study who received tivozanib had a median overall survival of 28.8 months, particularly given that these patients received minimal subsequent therapy,” said principal investigator Robert J Motzer, MD, attending physician, genitourinary oncology service, Memorial Sloan-Kettering Cancer Centre, and professor of medicine, Weill Medical College, Cornell University, New York. “The safety and efficacy results from TIVO-1 and other clinical trials of tivozanib in advanced RCC suggest it may provide an important new first line treatment option for patients with this aggressive disease.”

In TIVO-1, tivozanib demonstrated a statistically significant improvement in progression-free survival (PFS), the primary endpoint of the study, when compared with sorafenib. The FDA has accepted the tivozanib NDA for filing, and according to the timelines established by the Prescription Drug User Fee Act (PDUFA), the review of the NDA is expected to be complete by July 28, 2013.

Other data being presented at ASCO GU shows the anti-tumour activity of tivozanib following treatment with sorafenib resulted in a median PFS of 8.4 months and response rate of 13 per cent.

“We believe that these data being presented at ASCO GU reinforce the positive efficacy results and safety profile of tivozanib in patients with advanced RCC,” said William Slichenmyer, MD, Sc.M., chief medical officer at AVEO.

“We are excited to be working with AVEO in our efforts to bring tivozanib to patients who are in need of new therapeutic options,” added Stephen Eck, MD, PhD., vice president of medical oncology, Astellas Pharma Global Development.

TIVO-1 is the first superiority pivotal study in first-line advanced RCC in which an investigational agent (tivozanib) has demonstrated statistically significant and clinically meaningful PFS superiority versus an approved targeted agent (sorafenib).

Eighty-six centres participated in the TIVO-1 study, including centres in Europe and North America. The primary efficacy endpoint (PFS) was ascertained for each subject by a central panel of blinded independent radiologists. Patients randomized to the sorafenib arm of TIVO-1 were eligible to cross over to tivozanib therapy under a separate protocol after radiographic confirmation of disease progression. No crossover protocol was available for patients randomized to the tivozanib arm.

Tivozanib is a potent, selective and long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors that is designed to optimize VEGF blockade while minimizing off-target toxicities. Tivozanib is an oral, once-daily, investigational tyrosine kinase inhibitor for which positive results from a phase III clinical study in advanced RCC have been reported, and is being evaluated in other tumours.

In February 2011, AVEO and Astellas entered into a worldwide agreement to develop and commercialize tivozanib outside of Asia for the treatment of a broad range of cancers. Subject to regulatory approval, AVEO will lead commercialization of tivozanib in North America and Astellas will lead commercialization of tivozanib in the European Union (EU).

Astellas Pharma Inc., is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals.

AVEO Oncology is a cancer therapeutics company committed to discovering, developing and commercializing targeted therapies to impact patients' lives.