Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study. (May 2018)

• Record Type: Journal Article
• Authors: Molina, Ana M.; Hutson, Thomas E.; Nosov, Dmitry; Tomczak, Piotr; Lipatov, Oleg; Sternberg, Cora N.; Motzer, Robert; Eisen, Tim
• Is Part Of: European journal of cancer. Volume 94(2018)
• Page Start: 87
• Page End: 94
• Publication Date: 2018-05
• Subjects: Tivozanib -- Sorafenib -- First-line therapy -- Metastatic renal cell carcinoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.02.009
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: Tivozanib is a potent and selective inhibitor of vascular endothelial growth factor receptors. Tivozanib is approved by the European Commission for untreated renal cell carcinoma. Tivozanib previously demonstrated favourable clinical outcomes versus sorafenib. Tivozanib anti-tumour activity after progression on sorafenib is demonstrated. This crossover study provided clarity of the TIVO-1 trial overall survival results.