Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study
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Published:2013-10-01
Issue:28
Volume:31
Page:3509-3516
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Llovet Josep M.1, Decaens Thomas1, Raoul Jean-Luc1, Boucher Eveline1, Kudo Masatoshi1, Chang Charissa1, Kang Yoon-Koo1, Assenat Eric1, Lim Ho-Yeong1, Boige Valerie1, Mathurin Philippe1, Fartoux Laetitia1, Lin Deng-Yn1, Bruix Jordi1, Poon Ronnie T.1, Sherman Morris1, Blanc Jean-Frédéric1, Finn Richard S.1, Tak Won-Young1, Chao Yee1, Ezzeddine Rana1, Liu David1, Walters Ian1, Park Joong-Won1
Affiliation:
1. Josep M. Llovet and Charissa Chang, Icahn School of Medicine at Mount Sinai, New York, NY; Josep M. Llovet and Jordi Bruix, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) –Hospital Clinic, University of Barcelona, Barcelona, Spain; Thomas Decaens, University of Paris-Est, and Institut National de la Santé et de la Recherche Médicale, Creteil; Jean-Luc Raoul, Institut Paoli Calmette, Marseille; Eveline Boucher, Service d'Oncologie Médicale, Central Eugene Marquis, Rennes; Eric Assenat,...
Abstract
Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
519 articles.
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