Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study

被引:32
作者
Molina, Ana M. [1 ]
Hutson, Thomas E. [2 ]
Nosov, Dmitry [3 ]
Tomczak, Piotr [4 ]
Lipatov, Oleg [5 ]
Sternberg, Cora N. [6 ]
Motzer, Robert [7 ]
Eisen, Tim [8 ]
机构
[1] Weill Cornell Med, 520 East 70th St,Starr Pavil,3rd Floor, New York, NY 10065 USA
[2] Texas Oncol Baylor Charles A Sammons Canc Ctr, 3410 Worth St,Suite 400, Dallas, TX 75254 USA
[3] NN Blokhin Canc Res Ctr, Dept Clin Pharmacol & Chemotherapy, 24 Kashirskoye Shosse, Moscow 115478, Russia
[4] Poznan Univ Med Sci, Clin Hosp 1, Szamarzewskiego 82-84, PL-60569 Poznan, Poland
[5] Republican Clin Oncol Dispensary, 73-1 Oktiabria Pr, Ufa 450054, Russia
[6] San Camillo Forlanini Hosp, Padiglione Flajani, Dept Med Oncol, 1st Floor,Circonvallaz Gianicolense 87, I-00152 Rome, Italy
[7] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA
[8] Cambridge Univ Hlth Partners, R4 Block,Box 193,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England
关键词
Tivozanib; Sorafenib; First-line therapy; Metastatic renal cell carcinoma; RECEPTOR TYROSINE KINASES; ANTITUMOR-ACTIVITY; TARGETED THERAPY; INTERFERON-ALPHA; MANAGEMENT; EVEROLIMUS; INHIBITOR; SUNITINIB; SURVIVAL; AV-951;
D O I
10.1016/j.ejca.2018.02.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2018 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:87 / 94
页数:8
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