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 (US)
JournalJournal of Hepatology
DOIs
StateAccepted/In press - Mar 19 2015

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Keywords

  • HCC
  • Sorafenib
  • TACE

ASJC Scopus subject areas

  • Hepatology

Cite this

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. (Accepted/In press). Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2016.01.012