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

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• 作者：Riccardo Lencioni¹ ; ² ; ^&dagger ; ; ^&Dagger ; ; ^{rlencioni@med.miami.edu" class="auth_mail" title="E-mail the corresponding author} ; Josep M. Llovet³ ; ⁴ ; ⁵ ; ^&dagger ; ; Guohong Han⁶ ; Won Young Tak⁷ ; Jiamei Yang⁸ ; Alfredo Guglielmi⁹ ; Seung Woon Paik¹⁰ ; Maria Reig³ ; Do Young Kim¹¹ ; Gar-Yang Chau¹² ; Angelo Luca¹³ ; Luis Ruiz del Arbol¹⁴ ; Marie-Aude Leberre¹⁵ ; Woody Niu¹⁶ ; Kate Nicholson¹⁷ ; Gerold Meinhardt¹⁸ ; Jordi Bruix³ ; ^&dagger ;
• 关键词：Sorafenib ; TACE ; HCC
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：64
• 期：5
• 页码：1090-1098
• 全文大小：835 K

文摘

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.