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

Riccardo Lencioni; Josep M. Llovet; Guohong Han; Won Young Tak; Jiamei Yang; Alfredo Guglielmi; Seung Woon Paik; Maria Reig; Do Young Kim; Gar Yang Chau; Angelo Luca; Luis Ruiz Del Arbol; Marie Aude Leberre; Woody Niu; Kate Nicholson; Gerold Meinhardt; Jordi Bruix

doi:10.1016/j.jhep.2016.01.012

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

Riccardo Lencioni, Josep M. Llovet, Guohong Han, Won Young Tak, Jiamei Yang, Alfredo Guglielmi, Seung Woon Paik, Maria Reig, Do Young Kim, Gar Yang Chau, Angelo Luca, Luis Ruiz Del Arbol, Marie Aude Leberre, Woody Niu, Kate Nicholson, Gerold Meinhardt, Jordi Bruix

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

433 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1090-1098
Number of pages	9
Journal	Journal of Hepatology
Volume	64
Issue number	5
DOIs	https://doi.org/10.1016/j.jhep.2016.01.012
Publication status	Published - 2016 May 1

Bibliographical note

Funding Information:
Riccardo Lencioni has received honoraria from Bayer HealthCare and Biocompatibles UK Ltd, and research funding from Bayer HealthCare; Josep M. Llovet has received consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Bristol-Myers-Squibb, Biocompatibles, Imclone-Lilly, and Novartis; and research funding from Bayer HealthCare Pharmaceuticals, Boehringer-Ingelheim, and Bristol-Myers-Squibb; Guohong Han, Won Young Tak, Jiamei Yang, Alfredo Guglielmi, Seung Woon Paik, Do Young Kim, Gar-Yang Chau, Angelo Luca, and Luis Ruiz del Arbol have no relevant relationships to disclose; Maria Reig has received consulting fees and honoraria from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals; Marie-Aude Leberre, Woody Niu, Kate Nicholson, and Gerold Meinhardt are employees of Bayer HealthCare Pharmaceuticals; Jordi Bruix has received honoraria and research funding from Bayer HealthCare Pharmaceuticals and consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Biocompatibles, Bristol-Myers Squibb, Glaxo, Kowa, Novartis, and ArQule.

Publisher Copyright:
© 2016 European Association for the Study of the Liver.

All Science Journal Classification (ASJC) codes

Hepatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jhep.2016.01.012

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Lencioni, R., Llovet, J. M., Han, G., Tak, W. Y., Yang, J., Guglielmi, A., Paik, S. W., Reig, M., Kim, D. Y., Chau, G. Y., Luca, A., Del Arbol, L. R., Leberre, M. A., Niu, W., Nicholson, K., Meinhardt, G., & Bruix, J. (2016). Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. Journal of Hepatology, 64(5), 1090-1098. https://doi.org/10.1016/j.jhep.2016.01.012

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

abstract = "Background & Aims Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead{\textregistered}; 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.",

author = "Riccardo Lencioni and Llovet, {Josep M.} and Guohong Han and Tak, {Won Young} and Jiamei Yang and Alfredo Guglielmi and Paik, {Seung Woon} and Maria Reig and Kim, {Do Young} and Chau, {Gar Yang} and Angelo Luca and {Del Arbol}, {Luis Ruiz} and Leberre, {Marie Aude} and Woody Niu and Kate Nicholson and Gerold Meinhardt and Jordi Bruix",

note = "Funding Information: Riccardo Lencioni has received honoraria from Bayer HealthCare and Biocompatibles UK Ltd, and research funding from Bayer HealthCare; Josep M. Llovet has received consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Bristol-Myers-Squibb, Biocompatibles, Imclone-Lilly, and Novartis; and research funding from Bayer HealthCare Pharmaceuticals, Boehringer-Ingelheim, and Bristol-Myers-Squibb; Guohong Han, Won Young Tak, Jiamei Yang, Alfredo Guglielmi, Seung Woon Paik, Do Young Kim, Gar-Yang Chau, Angelo Luca, and Luis Ruiz del Arbol have no relevant relationships to disclose; Maria Reig has received consulting fees and honoraria from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals; Marie-Aude Leberre, Woody Niu, Kate Nicholson, and Gerold Meinhardt are employees of Bayer HealthCare Pharmaceuticals; Jordi Bruix has received honoraria and research funding from Bayer HealthCare Pharmaceuticals and consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Biocompatibles, Bristol-Myers Squibb, Glaxo, Kowa, Novartis, and ArQule. Publisher Copyright: {\textcopyright} 2016 European Association for the Study of the Liver.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.jhep.2016.01.012",

language = "English",

volume = "64",

pages = "1090--1098",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

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Lencioni, R, Llovet, JM, Han, G, Tak, WY, Yang, J, Guglielmi, A, Paik, SW, Reig, M, Kim, DY, Chau, GY, Luca, A, Del Arbol, LR, Leberre, MA, Niu, W, Nicholson, K, Meinhardt, G & Bruix, J 2016, 'Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial', Journal of Hepatology, vol. 64, no. 5, pp. 1090-1098. https://doi.org/10.1016/j.jhep.2016.01.012

TY - JOUR

T1 - Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC

T2 - The SPACE trial

AU - Lencioni, Riccardo

AU - Llovet, Josep M.

AU - Han, Guohong

AU - Tak, Won Young

AU - Yang, Jiamei

AU - Guglielmi, Alfredo

AU - Paik, Seung Woon

AU - Reig, Maria

AU - Kim, Do Young

AU - Chau, Gar Yang

AU - Luca, Angelo

AU - Del Arbol, Luis Ruiz

AU - Leberre, Marie Aude

AU - Niu, Woody

AU - Nicholson, Kate

AU - Meinhardt, Gerold

AU - Bruix, Jordi

N1 - Funding Information: Riccardo Lencioni has received honoraria from Bayer HealthCare and Biocompatibles UK Ltd, and research funding from Bayer HealthCare; Josep M. Llovet has received consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Bristol-Myers-Squibb, Biocompatibles, Imclone-Lilly, and Novartis; and research funding from Bayer HealthCare Pharmaceuticals, Boehringer-Ingelheim, and Bristol-Myers-Squibb; Guohong Han, Won Young Tak, Jiamei Yang, Alfredo Guglielmi, Seung Woon Paik, Do Young Kim, Gar-Yang Chau, Angelo Luca, and Luis Ruiz del Arbol have no relevant relationships to disclose; Maria Reig has received consulting fees and honoraria from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals; Marie-Aude Leberre, Woody Niu, Kate Nicholson, and Gerold Meinhardt are employees of Bayer HealthCare Pharmaceuticals; Jordi Bruix has received honoraria and research funding from Bayer HealthCare Pharmaceuticals and consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Biocompatibles, Bristol-Myers Squibb, Glaxo, Kowa, Novartis, and ArQule. Publisher Copyright: © 2016 European Association for the Study of the Liver.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

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EP - 1098

JO - Journal of Hepatology

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ER -

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

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Bibliographical note

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