title: Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial.
abstract: BACKGROUND
  The phase III Sorafenib Asia-Pacific (AP) trial-conducted in China, Taiwan and South Korea - confirmed that sorafenib improves overall survival (OS) and is safe for patients with advanced hepatocellular carcinoma (HCC). We performed a series of exploratory subset analyses to determine whether baseline status affected response to sorafenib.
  
  
  METHODS
  In the Sorafenib AP trial, 226 patients with well-preserved liver function (>95% Child-Pugh A) were randomised 2:1 to sorafenib 400mg bid or matching placebo. Subanalyses were based on aetiology (hepatitis B virus present/absent); tumour burden (macroscopic vascular invasion and/or extrahepatic spread present/absent); presence or absence of either lung or lymph node metastasis at baseline, Eastern Cooperative Oncology Group performance status (0, 1-2); serum concentrations of alanine aminotransferase/aspartate aminotransferase (normal, mildly elevated, moderately elevated), alpha-fetoprotein (normal/elevated) and total bilirubin (normal/elevated); and whether or not there was a history of hepatectomy or transarterial chemoembolisation/embolisation. Subgroup assessments included OS, time to progression (TTP), disease control rate and safety.
  
  
  RESULTS
  Sorafenib consistently improved both median OS and median TTP, compared with placebo (range of hazard ratios (HR), 0.32-0.87 and 0.31-0.75, respectively). The most common grade 3/4 adverse events were hand-foot skin reaction, diarrhoea and fatigue, the incidence of which was similar between subgroups.
  
  
  CONCLUSIONS
  The efficacy and safety profiles of sorafenib in the subpopulations described were comparable with those in the overall study population. These exploratory analyses suggest that sorafenib is effective for patients from the AP region with advanced HCC, irrespective of baseline status.
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan. alcheng@ntu.edu.tw
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Guan
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Chen
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Tsao
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.forename: Jun Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Tsai-Sheng
authors.initials: TS
authors.lastname: Yang
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.forename: Shiying
authors.initials: S
authors.lastname: Yu
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Jessie
authors.initials: J
authors.lastname: Zou
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lentini
authors.forename: Dimitris
authors.initials: D
authors.lastname: Voliotis
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000328:Adult; D001557:Benzenesulfonates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002681:China; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010919:Placebos; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use*; D056910:Republic of Korea; D000077157:Sorafenib; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D010919:Placebos; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib