Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study

Philip J. Johnson, Shukui Qin, Joong Won Park, Ronnie T.P. Poon, Jean Luc Raoul, Philip A. Philip, Chih Hung Hsu, Tsung Hui Hu, Jeong Heo, Jianming Xu, Ligong Lu, Yee Chao, Eveline Boucher, Kwang Hyub Han, Seung Woon Paik, Jorge Robles-Aviña, Masatoshi Kudo, Lunan Yan, Abhasnee Sobhonslidsuk, Dmitry KomovThomas Decaens, Won Young Tak, Long Bin Jeng, David Liu, Rana Ezzeddine, Ian Walters, Ann Lii Cheng

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Abstract

Purpose: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC. Patients and Methods: Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety. Results: The primary end point of OS noninferiority for brivanib versus sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI limit for HR ≤ 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and 23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-footskin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a result of adverse events was 33% for sorafenib and 43% for brivanib; rates for dose reduction were 50% and 49%, respectively. Conclusion: 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.

Original languageEnglish
Pages (from-to)3517-3524
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number28
DOIs
Publication statusPublished - 2013 Oct 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Johnson, P. J., Qin, S., Park, J. W., Poon, R. T. P., Raoul, J. L., Philip, P. A., Hsu, C. H., Hu, T. H., Heo, J., Xu, J., Lu, L., Chao, Y., Boucher, E., Han, K. H., Paik, S. W., Robles-Aviña, J., Kudo, M., Yan, L., Sobhonslidsuk, A., ... Cheng, A. L. (2013). Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. Journal of Clinical Oncology, 31(28), 3517-3524. https://doi.org/10.1200/JCO.2012.48.4410