title: Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has demonstrated encouraging antitumor activity in preclinical and phase I studies. We performed a phase II open-label study of brivanib as first-line therapy in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma.
  
  
  METHODS
  Brivanib was administered orally at a dose of 800 mg once daily. The primary objective was 6-month progression-free survival, progression-free survival rate; secondary objectives were tumor response rate, time to response, duration of response, median progression-free survival, median overall survival, disease control rate (complete response, partial response, or stable disease ≥ 42 days), and safety and tolerability.
  
  
  RESULTS
  Between March 2007 and May 2009, 55 patients were treated and were evaluable for response. Patients were assessed using modified World Health Organization (mWHO) criteria. According to mWHO criteria and as assessed by Independent Response Review Committee, the six-month progression-free survival rate (95% CI) was 18.2% (9.1%-30.9%). Median progression-free survival (95% CI) was 2.7 months (1.4-3.0). One patient achieved a complete response and three achieved a partial response. Twenty-two had stable disease. Median overall survival (95% CI) was 10 (6.8-15.2) months. Brivanib was generally well tolerated; the most common adverse events included fatigue, hypertension, and diarrhea.
  
  
  CONCLUSIONS
  Brivanib as first-line therapy demonstrates promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC.
authors.affiliation: National Cancer Center, Goyang, Republic of Korea. jwpark@ncc.re.kr
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
authors.forename: Jun Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Mark
authors.initials: M
authors.lastname: Karwal
authors.forename: Ruby K
authors.initials: RK
authors.lastname: Li
authors.forename: Fuad
authors.initials: F
authors.lastname: Ismail
authors.forename: Melanie
authors.initials: M
authors.lastname: Thomas
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Harris
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.forename: Ian
authors.initials: I
authors.lastname: Walters
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D014227:Triazines; C509922:brivanib; D000409:Alanine