Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
MD Anderson Cancer Center, Houston, TX, USA.
Br J Cancer. 2020 Mar;122(7):963-970. doi: 10.1038/s41416-020-0737-6. Epub 2020 Feb 10.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. It is a highly vascular tumour with multiple angiogenic factors, most importantly vascular endothelial growth factor (VEGF), involved in HCC progression. Tivozanib is an oral inhibitor of VEGFR-1/2/3 with promising activity against HCC in vivo.
We conducted a phase 1b/2 study of tivozanib in patients with advanced HCC. The safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary antineoplastic efficacy of tivozanib were evaluated.
Twenty-seven patients received at least one dose of tivozanib. Using a 3+3 design, the recommended phase 2 dose (RP2D) of tivozanib was determined to be 1 mg per os once daily, 21 days on-7 days off. The median progression-free and overall survival were 24 weeks and 9 months, respectively, for patients treated at RP2D. The overall response rate was 21%. Treatment was well tolerated. A significant decrease in soluble plasma VEGFR-2 was noted, assuring adequate target engagement.
Although this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway.
ClinicalTrials.gov NCT01835223, registered on 15 April 2013.
肝细胞癌（HCC）是癌症相关死亡的主要原因。它是一种高度血管化的肿瘤，涉及多种血管生成因子，其中最重要的是血管内皮生长因子（VEGF），参与 HCC 的进展。替沃扎尼布是一种口服的 VEGFR-1/2/3 抑制剂，在体内对 HCC 具有有前景的活性。
我们进行了一项替沃扎尼布治疗晚期 HCC 患者的 1b/2 期研究。评估了替沃扎尼布的安全性、剂量、药代动力学、药效学和初步抗肿瘤疗效。
27 名患者接受了至少一剂替沃扎尼布。采用 3+3 设计，确定替沃扎尼布的推荐 2 期剂量（RP2D）为口服 1 毫克，每天一次，21 天用药，7 天停药。RP2D 治疗患者的中位无进展生存期和总生存期分别为 24 周和 9 个月。总缓解率为 21%。治疗耐受性良好。观察到可溶性血浆 VEGFR-2 显著下降，确保了充分的靶标结合。
尽管该研究未进入 2 期，但早期疗效信号良好，且毒性特征非常有利。目前正在进行替沃扎尼布联合度伐利尤单抗的 1/2 期试验。
ClinicalTrials.gov NCT01835223，于 2013 年 4 月 15 日注册。
