The present multicenter phase II trial investigated the combination of TACE and sorafenib for the treatment of HCC. Eligibility criteria included histologically confirmed, unresectable HCC beyond Milan criteria, no extrahepatic spread, Child–Pugh score ≤8 and ECOG PS 0-2. Patients had received no prior therapy for HCC. Sorafenib was given at a dose of 400 mg/bid (interrupted only around TACE). TACE with lipiodol, 50 mg doxorubicin and polyvinyl alcohol (PVA) particles was repeated q6w as long as there was no overall disease progression. Tumor assessment by MRI was performed q6w according to EASL criteria. The primary endpoint was time to progression (TTP). Patients (n = 43) received a mean of 2.6 ± 2.2 TACE interventions (range 0–10). Median TTP was 16.4 months (95 % CI 10.7–∞). Median overall survival (OS) was 20.1 months (95 % CI 17.6–28.2). Disease control rate according to EASL criteria was 74.4 % (7 % complete responses [CRs] + 41.8 % partial responses [PRs] + 25.6 % stable diseases [SDs]). Four patients (9 %) became amenable to either radiofrequency ablation or liver transplantation; 5 (12 %) patients died during the trial. Overall, there were 360 AEs, including 56 grade 3/4 AEs and 39 SAEs. Combination treatment of TACE and sorafenib in the present trial was tolerable and associated with an interesting response rate, TTP and OS. Combination therapies will probably close gaps in the present mono therapy driven treatment guidelines for locally advanced HCC.
