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

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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 languageEnglish
Pages (from-to)1090-1098
Number of pages9
JournalJournal of Hepatology
Volume64
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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Doxorubicin
Hepatocellular Carcinoma
Placebos
Survival
Neoplasms
Safety
sorafenib
Liver Neoplasms
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Lencioni, R., Llovet, J. M., Han, G., Tak, W. Y., Yang, J., Guglielmi, A., ... 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
Lencioni, Riccardo ; Llovet, Josep M. ; Han, Guohong ; Tak, Won Young ; Yang, Jiamei ; Guglielmi, Alfredo ; Paik, Seung Woon ; Reig, Maria ; Kim, Do Young ; Chau, Gar Yang ; Luca, Angelo ; Del Arbol, Luis Ruiz ; Leberre, Marie Aude ; Niu, Woody ; Nicholson, Kate ; Meinhardt, Gerold ; Bruix, Jordi. / Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC : The SPACE trial. In: Journal of Hepatology. 2016 ; Vol. 64, No. 5. pp. 1090-1098.
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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{\circledR}; 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",
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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

Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC : The SPACE trial. / Lencioni, Riccardo; Llovet, Josep M.; Han, Guohong; Tak, Won Young; Yang, Jiamei; Guglielmi, Alfredo; Paik, Seung Woon; Reig, Maria; Kim, Do Young; Chau, Gar Yang; Luca, Angelo; Del Arbol, Luis Ruiz; Leberre, Marie Aude; Niu, Woody; Nicholson, Kate; Meinhardt, Gerold; Bruix, Jordi.

In: Journal of Hepatology, Vol. 64, No. 5, 01.05.2016, p. 1090-1098.

Research output: Contribution to journalArticle

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

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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