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

JOURNAL OF HEPATOLOGY

卷:64

Article

Lencioni, Riccardo^1,2  Llovet, Josep M.^3,4,5  Han, Guohong⁶  Tak, Won Young⁷  Yang, Jiamei⁸  Guglielmi, Alfredo⁹  Paik, Seung Woon¹⁰  Reig, Maria³  Kim, Do Young¹¹  Chau, Gar-Yang¹²  Luca, Angelo¹³  Ruiz del Arbol, Luis¹⁴  Leberre, Marie-Aude¹⁵  Niu, Woody¹⁶  Nicholson, Kate¹⁷  Meinhardt, Gerold¹⁸  Bruix, Jordi³ 

[1] Univ Miami, Miller Sch Med, Miami, FL 33136 USA

[2] Univ Pisa, Sch Med, I-56100 Pisa, Italy

[3] Hosp Clin Barcelona, Liver Unit, IDIBAPS, BCLC Grp,CIBERehd, Barcelona, Spain

[4] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, New York, NY USA

[5] Inst Catalana Recerca & Estudis Avancats, Catalonia, Spain

[6] Fourth Mil Med Univ, Xijing Hosp, Xian 710032, Peoples R China

[7] Kyungpook Natl Univ Hosp, Daegu, South Korea

[8] Shanghai Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China

[9] Univ Verona, Sch Med, I-37100 Verona, Italy

[10] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea

[11] Yonsei Univ, Coll Med, Seoul, South Korea

[12] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Taipei 112, Taiwan

[13] Univ Pittsburgh, Med Ctr Italy, Mediterranean Inst Transplantat & Adv Specialized, Palermo, Italy

[14] Univ Alcala, Hosp Ramon y Cajal, Madrid, Spain

[15] Bayer HealthCare Pharmaceut, Loos, France

[16] Bayer HealthCare Co Ltd, Beijing, Peoples R China

[17] Bayer PLC, Newbury, Berks, England

[18] Bayer HealthCare Pharmaceut, Montville, NJ USA

关键词: Sorafenib;    TACE;    HCC;   

DOI  :  10.1016/j.jhep.2016.01.012

来源: Elsevier

【 摘 要 】

Background & Aims: Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead (R); 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 (TIP) 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 TIP 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 ORR5 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. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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