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

As an inhibitor of fibroblast growth factor receptor ( FGFR) - 1, FGFR- 2, FGFR- 3, vascular endothelial growth factor receptor ( 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 brivanib 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 trials 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 brivanib in the therapy for HCC.