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J Hepatol. 2016 May;64(5):1090-1098. doi: 10.1016/j.jhep.2016.01.012. Epub 2016 Jan 22.

Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial.

Author information

1
University of Miami Miller School of Medicine, Miami, FL, USA; Pisa University School of Medicine, Pisa, Italy. Electronic address: rlencioni@med.miami.edu.
2
Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, CIBERehd, Barcelona, Spain; Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York, NY, USA; Institució Catalana de Recerca i Estudis Avançats, Catalonia, Spain.
3
Xijing Hospital, Fourth Military Medical University, Xi'an, China.
4
Kyungpook National University Hospital, Daegu, South Korea.
5
Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
6
University of Verona Medical School, Verona, Italy.
7
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
8
Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, CIBERehd, Barcelona, Spain.
9
Yonsei University College of Medicine, Seoul, South Korea.
10
Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
11
Mediterranean Institute for Transplantation and Advanced Specialized Therapies, University of Pittsburgh Medical Center Italy, Palermo, Italy.
12
Hospital Ramón y Cajal, University of Alcalá, Madrid, Spain.
13
Bayer HealthCare Pharmaceuticals, Loos, France.
14
Bayer HealthCare Co, Ltd, Beijing, China.
15
Bayer Plc, Newbury, UK.
16
Bayer HealthCare Pharmaceuticals, Montville, NJ, USA.

Abstract

BACKGROUND & AIMS:

Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead®; DEB-TACE) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma (HCC). The multikinase inhibitor sorafenib enhances overall survival (OS) and time-to-tumor progression (TTP) in patients with advanced HCC. This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC.

METHODS:

Patients with intermediate stage multinodular HCC without macrovascular invasion (MVI) or extrahepatic spread (EHS) were randomized 1:1 to DEB-TACE (150 mg doxorubicin) plus sorafenib 400 mg twice daily or placebo. The primary endpoint was TTP by blinded central review. Secondary endpoints included time to MVI/EHS, OS, overall response rate (ORR) using modified response evaluation criteria in solid tumors, disease control rate (DCR), time to unTACEable progression (TTUP), and safety.

RESULTS:

Of 307 patients randomized, 154 received sorafenib and 153 received placebo. Median TTP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar (169 vs. 166 days, respectively; hazard ratio (HR) 0.797, p=0.072). Median time to MVI/EHS (HR 0.621, p=0.076) and OS (HR 0.898, p=0.29) had not been reached. The ORRs for patients in the sorafenib and placebo groups with post-baseline scans were 55.9% and 41.3%, respectively, and the DCRs were 89.2% and 76.1%, respectively. TTUP was lower with sorafenib than with placebo (HR 1.586; 95% confidence intervals, 1.200-2.096; median 95 vs. 224 days). No unexpected adverse events related to sorafenib were observed.

CONCLUSION:

Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00855218.

KEYWORDS:

HCC; Sorafenib; TACE

PMID:
26809111
DOI:
10.1016/j.jhep.2016.01.012
[Indexed for MEDLINE]

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