Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial
作者：Tim Meyer, Richard Fox, Yuk Ting, Paul J. Ross, Martin W. James, Richard Sturgess, Clive Stubbs, Deborah Stocken, Lucy Wall, Anthony Watkinson, Nigel Hacking, T.R. Jeffry Evans, Peter L. Collins, Richard Hubner, David Cunningham, John Primrose, Philip J. Johnson, Daniel H. Palmer · 发表于：The Lancet. Gastroenterology & hepatology · 年份：2017 · DOI：10.1016/s2468-1253(17)30156-5 · 被引用次数：504 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Liver Disease Diagnosis and Treatment、Organ Transplantation Techniques and Outcomes
BACKGROUND: Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo. METHODS: We did a multicentre, randomised, placebo-controlled, phase 3 trial (TACE 2) in 20 hospitals in the UK for patients with unresectable, liver-confined hepatocellular carcinoma. Patients were eligible if they were at least aged 18 years, had Eastern Cooperative Oncology Group performance status of 1 or less, and had Child-Pugh A liver disease. Patients were randomised 1:1 by computerised minimisation algorithm to continuous oral sorafenib (400 mg twice-daily) or matching placebo combined with TACE using drug-eluting beads (DEB-TACE), which was given via the hepatic artery 2-5 weeks after randomisation and according to radiological response and patient tolerance thereafter. Patients were stratified according to randomising centre and serum α-fetoprotein concentration (<400 ng/mL and ≥400 ng/mL). Only the trial coordinator was unmasked to treatment allocation before patient progression during the study. The primary endpoint was progression-free survival defined as the interval between randomisation and progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) or death due to any cause, and was an...