BACKGROUND: Tivozanib is a selective inhibitor of vascular endothelial growth 
factor receptors 1, 2 and 3 tyrosine kinases. This open-label, crossover 
clinical study (AV-951-09-902) provided access to tivozanib for patients who 
progressed on sorafenib in TIVO-1, comparing tivozanib with sorafenib in 
patients with advanced renal cell carcinoma (RCC).
METHODS: Patients enrolled in this single-arm, phase 2 crossover study were 
previously randomised to sorafenib on TIVO-1, progressed and then crossed over 
to tivozanib. Patients received tivozanib (1.5 mg/day orally; 3 weeks on/1 week 
off) within 4 weeks after their last sorafenib dose.
FINDINGS: Crossover patients were exposed to tivozanib for a median of eight 
cycles. From the start of tivozanib treatment, median progression-free survival 
was 11.0 months (95% confidence interval [CI]: 7.3-12.7) and median overall 
survival was 21.6 months (95% CI: 17.0-27.6). Best overall response was partial 
response in 29 (18%) patients and stable disease in 83 (52%) patients, with a 
median duration of response of 15.2 and 12.7 months, respectively. About 77% of 
patients experienced adverse events, most frequently hypertension (26%), 
followed by diarrhoea (14%) and fatigue (13%); 53% of patients had 
treatment-related adverse events, including 24% grade ≥3. About 9% and 16% of 
patients had dose reductions and dose interruptions due to adverse events, 
respectively. A total of 30% of patients had serious adverse events, and 4% had 
treatment-related serious adverse events.
INTERPRETATION: This crossover study of patients with advanced RCC demonstrated 
potent tivozanib anti-tumour activity. Safety and tolerability profiles were 
acceptable and consistent with the established adverse event profile of 
tivozanib.