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.
Bibliographical noteFunding 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.
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