Journal ArticleDOI
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.
Ann-Lii Cheng,Yoon-Koo Kang,Zhendong Chen,Chao Jung Tsao,Shukui Qin,Jun Suk Kim,Rongcheng Luo,Jifeng Feng,Sheng-Long Ye,Tsai Sheng Yang,Jianming Xu,Yan Sun,Houjie Liang,Jiwei Liu,Jiejun Wang,Won Young Tak,Hongming Pan,Karin Burock,Jessie Zou,D. Voliotis,Zhongzhen Guan +20 more
TLDR
Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated.Abstract:
Summary 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.read more
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Journal ArticleDOI
EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma
Peter R. Galle,Alejandro Forner,Josep M. Llovet,Vincenzo Mazzaferro,Fabio Piscaglia,Jean-Luc Raoul,Peter Schirmacher,Valérie Vilgrain +7 more
TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.
Journal ArticleDOI
Management of hepatocellular carcinoma: An update
Jordi Bruix,Morris Sherman +1 more
TL;DR: The American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) were updated in 2010 as discussed by the authors.
AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update
Jordi Bruix,Morris Sherman +1 more
TL;DR: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated.
Journal ArticleDOI
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
Masatoshi Kudo,Richard S. Finn,Shukui Qin,Kwang Hyub Han,Kenji Ikeda,Fabio Piscaglia,Ari David Baron,Joong-Won Park,Guohong Han,Jacek Jassem,Jean-Frédéric Blanc,Arndt Vogel,Dmitry Komov,T.R. Jeffry Evans,Carlos Lopez,Corina E. Dutcus,Matthew Guo,Kenichi Saito,Silvija Kraljevic,Toshiyuki Tamai,Min Ren,Ann-Lii Cheng +21 more
TL;DR: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma and the safety and tolerability profiles of lenvatinIB were consistent with those previously observed.
Journal ArticleDOI
Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial
Anthony B. El-Khoueiry,Bruno Sangro,Thomas Yau,Todd S. Crocenzi,Masatoshi Kudo,Chiun Hsu,Tae You Kim,Su Pin Choo,Jörg Trojan,Theodore H. Welling,Tim Meyer,Yoon-Koo Kang,Winnie Yeo,Akhil Chopra,Jeffrey Anderson,Christine Dela Cruz,Lixin Lang,Jaclyn Neely,Hao Tang,Homa Dastani,Ignacio Melero +20 more
TL;DR: Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma, and safety and tolerability for the escalation phase and objective response rate were primary endpoints.
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