title: Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone.
authors.affiliation: University of Miami Miller School of Medicine, Miami, FL, USA; Pisa University School of Medicine, Pisa, Italy. Electronic address: rlencioni@med.miami.edu.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lencioni
authors.affiliation: 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.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llovet
authors.affiliation: Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Han
authors.affiliation: Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Tak
authors.affiliation: Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Yang
authors.affiliation: University of Verona Medical School, Verona, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guglielmi
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.affiliation: Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Reig
authors.affiliation: Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Gar-Yang
authors.initials: GY
authors.lastname: Chau
authors.affiliation: Mediterranean Institute for Transplantation and Advanced Specialized Therapies, University of Pittsburgh Medical Center Italy, Palermo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Luca
authors.affiliation: Hospital Ramón y Cajal, University of Alcalá, Madrid, Spain.
authors.forename: Luis Ruiz
authors.initials: LR
authors.lastname: Del Arbol
authors.affiliation: Bayer HealthCare Pharmaceuticals, Loos, France.
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Leberre
authors.affiliation: Bayer HealthCare Co, Ltd, Beijing, China.
authors.forename: Woody
authors.initials: W
authors.lastname: Niu
authors.affiliation: Bayer Plc, Newbury, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Nicholson
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, NJ, USA.
authors.forename: Gerold
authors.initials: G
authors.lastname: Meinhardt
authors.affiliation: Barcelona Clínic Liver Cancer (BCLC) Group, Liver Unit, Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Hospital Clínic Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010671:Phenylurea Compounds; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib
keywords: HCC; Sorafenib; TACE