Weill Cornell Medicine, New York, NY, USA.
Texas Oncology-Baylor Charles A. Sammons Cancer Center, 3410 Worth Street, Suite 400, Dallas, TX, 75254, USA.
Eur J Cancer. 2018 May;94:87-94. doi: 10.1016/j.ejca.2018.02.009. Epub 2018 Mar 20.
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).
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.
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.
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.
替沃扎尼布是一种血管内皮生长因子受体 1、2 和 3 酪氨酸激酶的选择性抑制剂。这项开放标签、交叉临床研究（AV-951-09-902）为 TIVO-1 中接受索拉非尼治疗后进展的患者提供了替沃扎尼布治疗，比较了替沃扎尼布与晚期肾细胞癌（RCC）患者的索拉非尼。
本项单臂、2 期交叉研究的入组患者此前曾在 TIVO-1 中随机接受索拉非尼治疗，进展后交叉接受替沃扎尼布治疗。患者在最后一次索拉非尼剂量后 4 周内接受替沃扎尼布（每日 1.5 毫克口服；3 周给药/1 周停药）治疗。
交叉患者接受替沃扎尼布治疗的中位周期数为 8 个。从开始替沃扎尼布治疗起，中位无进展生存期为 11.0 个月（95%置信区间[CI]：7.3-12.7），中位总生存期为 21.6 个月（95%CI：17.0-27.6）。最佳总体缓解为 29 名（18%）患者的部分缓解和 83 名（52%）患者的疾病稳定，缓解持续时间分别为 15.2 个月和 12.7 个月。约 77%的患者发生不良反应，最常见的是高血压（26%），其次是腹泻（14%）和疲劳（13%）；53%的患者发生治疗相关不良反应，包括 24%的 3 级及以上不良反应。约 9%和 16%的患者因不良反应分别减少和中断剂量。共有 30%的患者发生严重不良事件，4%的患者发生与治疗相关的严重不良事件。
这项晚期 RCC 患者的交叉研究表明，替沃扎尼布具有强大的抗肿瘤活性。安全性和耐受性特征可接受，与替沃扎尼布已确定的不良事件特征一致。
