Brivanib Versus Sorafenib As First-Line Therapy in Patients With Unresectable, Advanced Hepatocellular Carcinoma: Results From the Randomized Phase III BRISK-FL Study

Abstract

Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.

Current management of hepatocellular carcinoma: An Eastern perspective

“…Brivanib, a selective dual inhibitor of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling, was associated with a median overall survival of 10 mo in a phase Ⅱ trial [87] and was considered a promising new drug for advanced HCC. However, the primary endpoint of brivanib not being non-inferior to sorafenib was not met in a subsequent phase Ⅲ trial (overall survival, 9.5 and 9.9 mo, respectively, P value is nonsignificant) [88] . The efficacy of brivanib in advanced HCC patients who were intolerant to sorafenib or failed to respond to sorafenib previously was also tested.…”

Assessment of treatment efficacy in hepatocellular carcinoma: Response rate, delay in progression or none of them

“…Thus, the key question in the Lencioni et al study would be the comparison between RECIST and mRECIST as recommended in the EASL-EORTC guidelines (1). The non-validation of complete responses is explained by the vasoconstrictive action of antiangiogenic agents such as as sorafenib [5], regorafenib [6], sunitinib [25] or brivanib [24,26]. They may reduce hepatic artery blood flow and as a result, provoke a reduction in intratumoral contrast uptake that may be optimistically read as necrosis, while it would merely reflect hypovascularization (Fig.…”

Looking Beyond Sorafenib to Treat Advanced Hepatocellular Carcinoma

“…4 There is a high rate of resistance and newer multi-kinase inhibitors have failed to show superiority over sorafenib. [5][6][7] Hence, there is an unmet need for new treatment approaches to advanced HCC. With improvements in pre-operative staging and surgical techniques, and better understanding of the molecular biology of HCC, many new strategies to treat advanced HCC are under evaluation.…”