title: Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has recently been shown to have activity as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This phase II open-label study assessed brivanib as second-line therapy in patients with advanced HCC who had failed prior antiangiogenic treatment.
  
  
  METHODS
  Brivanib was administered orally at a dose of 800 mg once daily. The primary objectives were tumor response rate, time to response, duration of response, progression-free survival, overall survival (OS), disease control rate, time to progression (TTP), and safety and tolerability.
  
  
  RESULTS
  Forty-six patients were treated. Best responses to treatment with brivanib (N = 46 patients) using modified World Health Organization criteria were partial responses for two patients (4.3%), stable disease for 19 patients (41.3%), and progressive disease for 19 patients (41.3%). The tumor response rate was 4.3%; the disease control rate was 45.7%. Median OS was 9.79 months. Median TTP as assessed by study investigators following second-line treatment with brivanib was 2.7 months. The most common adverse events were fatigue, decreased appetite, nausea, diarrhea, and hypertension.
  
  
  CONCLUSIONS
  Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced HCC patients treated with prior sorafenib.
authors.affiliation: Geffen School of Medicine, UCLA, Los Angeles, California, USA. rfinn@mednet.ucla.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Mary
authors.initials: M
authors.lastname: Mulcahy
authors.forename: Blase N
authors.initials: BN
authors.lastname: Polite
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Ian
authors.initials: I
authors.lastname: Walters
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.forename: Demetrios
authors.initials: D
authors.lastname: Manekas
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001066:Appetite / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D024141:Collagen Type IV / Q000097:blood; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D024141:Collagen Type IV; D014227:Triazines; D000509:alpha-Fetoproteins; C509922:brivanib; D000409:Alanine