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.

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.

• Authors: Ann-Lii Cheng, Zhongzhen Guan, Zhendong Chen, Chao-Jung Tsao, Shukui Qin, Jun Suk Kim, Tsai-Sheng Yang, Won Young Tak, Hongming Pan, Shiying Yu, Jianming Xu, Fang Fang, Jessie Zou, Giuseppe Lentini, Dimitris Voliotis, Yoon-Koo Kang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 48 Issue 10 Pg. 1452-65 (Jul 2012) ISSN: 1879-0852 [Electronic] England
• PMID: 22240282 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Benzenesulfonates
• Phenylurea Compounds
• Placebos
• Pyridines
• Niacinamide
• Sorafenib

Topics

• Adult
• Benzenesulfonates (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy)
• China
• Female
• Humans
• Liver Neoplasms (drug therapy)
• Male
• Middle Aged
• Neoplasm Metastasis
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Placebos
• Prognosis
• Pyridines (therapeutic use)
• Republic of Korea
• Sorafenib
• Taiwan
• Time Factors
• Treatment Outcome