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.
Author(s): Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S,
Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK.
Affiliation(s): National Taiwan University Hospital, Taipei, Taiwan. alcheng@ntu.edu.tw
Publication date & source: 2012, Eur J Cancer. , 48(10):1452-65
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.
FINDINGS: 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.
INTERPRETATION: 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.
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