Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial - 07/08/11
, Yoon-Koo Kang, MD b, Zhendong Chen, MD c, Chao-Jung Tsao, MD d, Shukui Qin, MD e, Jun Suk Kim, MD f, Rongcheng Luo, MD g, Jifeng Feng, MD h, Shenglong Ye, MD i, Tsai-Sheng Yang, MD j, Jianming Xu, MD k, Yan Sun, MD l, Houjie Liang, MD m, Jiwei Liu, MD n, Jiejun Wang, MD o, Won Young Tak, MD p, Hongming Pan, MD q, Karin Burock, BS r, Jessie Zou, MD s, Dimitris Voliotis, MD t, Zhongzhen Guan, MD uSummary |
Background |
Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma.
Methods |
Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752.
Findings |
271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6·5 months (95% CI 5·56–7·56) in patients treated with sorafenib, compared with 4·2 months (3·75–5·46) in those who received placebo (hazard ratio [HR] 0·68 [95% CI 0·50–0·93]; p=0·014). Median TTP was 2·8 months (2·63–3·58) in the sorafenib group compared with 1·4 months (1·35–1·55) in the placebo group (HR 0·57 [0·42–0·79]; p=0·0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10·7%]), diarrhoea (nine patients [6·0%]), and fatigue (five patients [3·4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11·4%]) and diarrhoea (11 patients [7·4%]); these adverse events rarely led to discontinuation.
Interpretation |
Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma.
Funding |
Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc.
Le texte complet de cet article est disponible en PDF.Plan
Vol 10 - N° 1
P. 25-34 - janvier 2009 Retour au numéro
Article précédent
- Ball: One man. One ball. One hour
- Talha Burki
- Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis
- Vincenzo Mazzaferro, Josep M Llovet, Rosalba Miceli, Sherrie Bhoori, Marcello Schiavo, Luigi Mariani, Tiziana Camerini, Sasan Roayaie, Myron E Schwartz, Gian Luca Grazi, René Adam, Peter Neuhaus, Mauro Salizzoni, Jordi Bruix, Alejandro Forner, Luciano De Carlis, Umberto Cillo, Andrew K Burroughs, Roberto Troisi, Massimo Rossi, Giorgio E Gerunda, Jan Lerut, Jacques Belghiti, Ilka Boin, Jean Gugenheim, Fedja Rochling, Bart Van Hoek, Pietro Majno, on behalf of the Metroticket Investigator Study Group ‡
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?