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J Clin Oncol. 2013 Oct 1;31(28):3517-24. doi: 10.1200/JCO.2012.48.4410. Epub 2013 Aug 26.

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

Author information

1
Philip J. Johnson, University of Birmingham, Birmingham, United Kingdom; Shukui Qin, Nanjing Bayi Hospital, Nanjing; Jianming Xu, 307 Hospital of PLA, Beijing; Ligong Lu, Guangdong Provincial People's Hospital, Guangdong; Lunan Yan, West China Hospital of Sichuan University, Chengdu; Ronnie T.P. Poon, University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China; Joong Won Park, Center for Liver Cancer, National Cancer Center, Goyang; Jeong Heo, Pusan National University School of Medicine, Pusan; Kwang Hyub Han, Yonsei University College of Medicine; Seung Woon Paik, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Won Young Tak, Kyungpook National University Hospital, Daegu, Republic of Korea; Jean-Luc Raoul, Institut Paoli Calmettes, Marseille; Eveline Boucher, Central Eugene Marquis, Rennes Cedex, Rennes; Thomas Decaens, Hôpital Henri Mondor, University of Paris-Est, and INSERM, Creteil Cedex, Creteil, France; Philip A. Philip, Karmanos Cancer Center, Detroit, MI; David Liu, Rana Ezzeddine, Ian Walters, Bristol-Myers Squibb, Princeton, NJ; Chih-Hung Hsu, Ann-Lii Cheng, National Taiwan University Hospital; Yee Chao, Cancer Center, Taipei Veterans General Hospital, Taipei; Tsung-Hui Hu, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung; Long-Bin Jeng, China Medical University Hospital, Taichung, Taiwan, Republic of China; Jorge Robles-Aviña, High Specialty Central South Hospital, Mexico City, Mexico; Masatoshi Kudo, Kinki University School of Medicine, Osaka, Japan; Abhasnee Sobhonslidsuk, Ramathibodi Hospital, Bangkok, Thailand; Dmitriy Komov, N.N. Blokhin Cancer Research Center, Moscow, Russia.

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-foot-skin 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00858871.

PMID:
23980084
DOI:
10.1200/JCO.2012.48.4410
[Indexed for MEDLINE]

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