PMID- 23980090
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20220409
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 28
DP  - 2013 Oct 1
TI  - 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.
PG  - 3509-16
LID - 10.1200/JCO.2012.47.3009 [doi]
AB  - 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.
FAU - Llovet, Josep M
AU  - Llovet JM
AD  - 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 Biomediques 
      August Pi i Sunyer (IDIBAPS) -Hospital Clinic, University of Barcelona, 
      Barcelona, Spain; Thomas Decaens, University of Paris-Est, and Institut National 
      de la Sante et de la Recherche Medicale, Creteil; Jean-Luc Raoul, Institut Paoli 
      Calmette, Marseille; Eveline Boucher, Service d'Oncologie Medicale, Central 
      Eugene Marquis, Rennes; Eric Assenat, Hopital Saint Eloi, Montpellier; Valerie 
      Boige, Institut Gustave Roussy, Villejuif; Philippe Mathurin, Hopital Claude 
      Huriez, Lille; Laetitia Fartoux, Hopital Saint Antoine, Paris; Jean-Frederic 
      Blanc, Saint-Andre Hospital, Bordeaux, France; Masatoshi Kudo, Kinki University 
      School of Medicine, Osaka, Japan; Yoon-Koo Kang, Asan Medical Center; Ho-Yeong 
      Lim, Samsung Medical Center, Seoul; Won-Young Tak, Kyungpook National University 
      Hospital, Daegu; Joong-Won Park, National Cancer Center, Goyang, Republic of 
      Korea; Deng-Yn Lin, Chang Gung Memorial Hospital and Chang Gung University; Yee 
      Chao, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; Ronnie 
      T. Poon, University of Hong Kong, Hong Kong Special Administrative Region, 
      People's Republic of China; Morris Sherman, Toronto General Hospital, Toronto, 
      Ontario, Canada; Richard S. Finn, University of California at Los Angeles, Los 
      Angeles, CA; and Rana Ezzeddine, David Liu, and Ian Walters, Bristol-Myers 
      Squibb, Wallingford, CT.
FAU - Decaens, Thomas
AU  - Decaens T
FAU - Raoul, Jean-Luc
AU  - Raoul JL
FAU - Boucher, Eveline
AU  - Boucher E
FAU - Kudo, Masatoshi
AU  - Kudo M
FAU - Chang, Charissa
AU  - Chang C
FAU - Kang, Yoon-Koo
AU  - Kang YK
FAU - Assenat, Eric
AU  - Assenat E
FAU - Lim, Ho-Yeong
AU  - Lim HY
FAU - Boige, Valerie
AU  - Boige V
FAU - Mathurin, Philippe
AU  - Mathurin P
FAU - Fartoux, Laetitia
AU  - Fartoux L
FAU - Lin, Deng-Yn
AU  - Lin DY
FAU - Bruix, Jordi
AU  - Bruix J
FAU - Poon, Ronnie T
AU  - Poon RT
FAU - Sherman, Morris
AU  - Sherman M
FAU - Blanc, Jean-Frederic
AU  - Blanc JF
FAU - Finn, Richard S
AU  - Finn RS
FAU - Tak, Won-Young
AU  - Tak WY
FAU - Chao, Yee
AU  - Chao Y
FAU - Ezzeddine, Rana
AU  - Ezzeddine R
FAU - Liu, David
AU  - Liu D
FAU - Walters, Ian
AU  - Walters I
FAU - Park, Joong-Won
AU  - Park JW
LA  - eng
SI  - ClinicalTrials.gov/NCT00825955
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130826
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Triazines)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - DDU33B674I (brivanib)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
CIN - J Clin Oncol. 2013 Oct 1;31(28):3483-6. PMID: 23980088
CIN - J Clin Oncol. 2014 Mar 20;32(9):968. PMID: 24516020
CIN - J Clin Oncol. 2014 Mar 20;32(9):968-9. PMID: 24516037
CIN - J Hepatol. 2014 Oct;61(4):947-50. PMID: 24972045
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alanine/*analogs & derivatives/therapeutic use
MH  - Carcinoma, Hepatocellular/*drug therapy/mortality/pathology
MH  - Double-Blind Method
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Niacinamide/adverse effects/*analogs & derivatives
MH  - Phenylurea Compounds/*adverse effects
MH  - Prognosis
MH  - Protein Kinase Inhibitors/*adverse effects
MH  - *Salvage Therapy
MH  - Sorafenib
MH  - Survival Rate
MH  - Triazines/*therapeutic use
MH  - Young Adult
EDAT- 2013/08/28 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/08/28 06:00
PHST- 2013/08/28 06:00 [entrez]
PHST- 2013/08/28 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - JCO.2012.47.3009 [pii]
AID - 10.1200/JCO.2012.47.3009 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Oct 1;31(28):3509-16. doi: 10.1200/JCO.2012.47.3009. Epub 2013 
      Aug 26.