A phase three trial showed that an already approved drug, sorafenib (Nexavar, manufactured by Bayer Pharma), and tivozanib share a similar survival period for patients with advanced renal cell cancer.
Sorafenib, also used for liver cancer, is a treatment for advanced renal cell cancer, and patients use it after earlier treatments with interferon-α or interleukin-2 have failed or if physicians deem these treatments inadequate. Sorafenib is a multikinase inhibitor (a tyrosine kinase inhibitor, an angiogenesis inhibitor, and a vascular endothelial growth factor [VEGF] inhibitor).
Tivozanib, the study drug, is a selective inhibitor of all three VEGF receptors that was designed to block VEGF while minimizing toxicities to other areas. Tivozanib is an oral, once-daily investigational tyrosine kinase inhibitor. Earlier, the TIVO-1 trial showed positive top-line results in advanced renal cell cancer, and the agent is being studied for use against other tumors.
Tivozanib and sorafenib treatment for patients with advanced renal cell carcinoma showed statistically similar overall survival, according to research reported at the Genitourinary Cancers Symposium by Robert J. Motzer, MD, a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.
At the time of final overall survival analysis, which was 2 years after the last patient was enrolled, 219 subjects had died: 118 (45.4 percent) in the tivozanib arm and 101 (39.3 percent) in the sorafenib arm. The median survival rates were 28.8 months for tivozanib and 29.3 months for sorafenib, which was not a significant difference.
Of the 257 patients taking sorafenib at randomization, more than half, (155, or 60.3 percent) had started taking next-line tivozanib by the time the data were analyzed.
Lead researcher Motzer presented final overall survival data from 1517 patients who were randomized to receive either tivozanib 1.5 mg a day (3 weeks on, 1 week off) or sorafenib 400 mg a day (twice daily, continuously), according to PharmPro.com. In the extension study, patients who experienced progression while taking sorafenib were eligible to receive tivozanib, which researchers said may account for a slightly longer survival time in the patients taking sorafenib.
Some side effects that bother renal cancer patients, including skin toxicity, diarrhea, nausea, and fatigue, were not as common with tivozanib. The lower toxicity and rate of side effects were positive features for a first-line therapy for advanced kidney cancer, Motzer said.
The manufacturers of tivozanib, AVEO Pharmaceuticals in Cambridge, MA, and Astellas Pharma, Inc., in Tokyo, were excited about the news when safety and other data from the study TIVO-1 were announced in 2012. “We are delighted with the outcome of TIVO-1 and to be collaborating with AVEO on tivozanib at this critical juncture,” said Steven Ryder, MD, president of Astellas Pharma Global Development. “Tivozanib is an important asset to our strategy of becoming a global category leader in oncology.”