Tivozanib, sorafenib found to extend survival in advanced renal cell carcinoma patients

Tivozanib and sorafenib extended survival in advanced renal cell carcinoma (RCC) patients with no statistical difference, according to the phase 3 TIVO-1 (TIvozanib Versus sOrafenib in 1st Line Advanced RCC) trial data, presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), in Orlando, Fla., in February.

Advanced RCC is the ninth most commonly diagnosed cancer in men and women in the United States. Worldwide it is estimated that more than 250,000 people are diagnosed and more than 100,000 people die from the disease each year. RCC accounts for more than 90% of all kidney cancers.

TIVO-1 is a randomized superiority-designed pivotal trial evaluating the efficacy and safety of tivozanib compared to sorafenib in 517 patients with advanced RCC who had no prior treatment with a VEGF inhibitor therapy. The OS analysis, conducted 2 years after the last patient was enrolled per the study protocol, showed that tivozanib and sorafenib extended survival in advanced renal cell cancer (RCC) patients with no statistical difference (HR=1.245, P=.105). Specifically, results showed a median OS of 28.8 months (95% CI: 22.5–NA) for tivozanib versus a median OS of 29.3 months (95% CI: 29.3–NA) for the comparator arm, sorafenib.  

A New Drug Application (NDA) has been submitted for tivozanib (AVEO Oncology, in partnership with Astellas Pharma) for treating patients with advanced RCC; the NDA filing was accepted by FDA for review on November 28, 2012. The NDA includes the results of TIVO-1, as well as data from 16 additional studies involving more than 1,000 subjects who received tivozanib.

“It’s encouraging to see that patients in the study who received tivozanib had a median overall survival of 28.8 months versus a median overall survival of 29.3 months for patients receiving sorafenib, particularly given that the tivozanib patients received minimal subsequent therapy,” said principal investigator Robert J. Motzer, MD, attending physician, genitourinary oncology service, Memorial Sloan-Kettering Cancer Center, and professor of medicine, Weill Medical College, Cornell University, New York.

Within the past year, TIVO-1 data have been presented at the American Society of Clinical Oncology and the European Society for Medical Oncology annual meetings. These data showed that tivozanib met the primary end point of the TIVO-1 study (superiority in progression-free survival [PFS] in patients taking tivozanib versus patients taking sorafenib). Patients taking tivozanib also experienced fewer Grade 3 and off-target adverse events, were observed to stay on treatment longer, and required fewer dose reductions and interruptions compared with those treated with sorafenib.

Other TIVO-1 data presented at ASCO GU showed the anti-tumor activity of tivozanib following treatment with sorafenib, which resulted in a median PFS of 8.4 months and response rate of 13%.

Despite advances in therapy for kidney cancer, the need persists for the continued development of effective treatments with manageable side effects. Minimizing toxicities from treatment, while maintaining efficacy, is still a significant concern for clinicians and RCC patients because adverse events may prevent patients from benefiting from the full effect of their medications.

Across the entire TIVO-1 study population, the most common adverse event (all grades) for tivozanib was hypertension (44% in tivozanib vs 34% in sorafenib), and for sorafenib was hand-foot syndrome (13% in tivozanib vs 54%in sorafenib). Other adverse events included diarrhea (22% vs 32%, respectively), fatigue (18% vs 16%, respectively), and neutropenia (10% vs 9%, respectively).