Brivanib治疗肝癌的临床研究进展

Brivanib for treatment of hepatocellular carcinoma: an overview of clinical trials

Brivanib可同时抑制成纤维细胞生长因子受体(FGFR)-1、FGFR-2、FGFR-3、血管内皮细胞生长因子受体(VEGFR)-2和VEGFR-3,以达到抑制肿瘤新生血管形成及肿瘤细胞生长的作用。旨在总结Brivanib治疗肝癌的进展,已完成的Ⅰ和Ⅱ期临床试验结果均证实了Brivanib在肝癌治疗中的安全性和有效性。然而,1项已完成的Ⅲ期随机双盲安慰剂对照研究表明,Brivanib作为晚期肝癌二线治疗手段(即Sorafenib治疗失败者)并未显著改善患者的总体生存期。另1项Ⅲ期随机双盲对照试验结果也表明,Brivanib作为晚期肝癌一线治疗手段并未比Sorafenib显著改善患者的总体生存期。这2项临床试验的失败使得其他两项有关Brivanib治疗肝癌的临床试验提前终止。通过分析以上研究认为亚组分析以及事先筛选Brivanib可能获益的肝癌患者(即FGF信号途径激活的肝癌患者)也许对进一步探究Brivanib的在肝癌治疗中的角色是必要的。

As an inhibitor of fibroblast growth factor receptor （FGFR） - 1, FGFR - 2, FGFR - 3, vascular endothelial growth factor recep tor （VEGFR） -2, and VEGFR- 3, brivanib can inhibit tumor angiogenesis and growth. Phase Ⅰ and Ⅱ clinical trials have demonstrated the safety and efficacy of bfivanib in the treatment of hepatocellular carcinoma （HCC）. However, one phase Ⅲ, randomized, double blind, placebo - controlled study showed that the overall survival was not significantly improved in patients receiving brivanib as a second - line therapy for advanced HCC, who had failed treatment with sorafenib, than in those receiving placebo. Another phase Ⅲ, randomized, double - blind, controlled study also showed that the overall survival was not significantly improved in patients receiving brivanib as a first - line therapy for HCC than in those receiving sorafenib. Due to the failure of the two phase Ⅲ studies, two other ongoing phase Ⅲ clinical tri als had to be discontinued. Subgroup analysis and prior selection of patients with FGF who might benefit from brivanib may be necessary for further investigation of bfivanib in the therapy for HCC.