Sorafenib and transarterial chemoembolization (TACE) alone and in combination have been used in patients with unresectable hepatocellular carcinoma (HCC); however, the effects of addition of sorafenib on the interval to subsequent TACE are unknown. The aim of this prospective, nonrandomized, comparative study was to examine the impact of concurrent TACE + sorafenib on overall survival (OS), time to progression (TTP), and the interval between courses of TACE.
This study enrolled 150 patients with unresectable HCC, including 50 patients in the TACE + sorafenib group and 100 patients in the TACE group, from June 2011 to June 2014. Patients in the TACE + sorafenib group received an initial dose of 400 mg administered orally twice a day, which was reduced or temporarily suspended in the event of an adverse event (AE). The factors associated with OS and TTP were identified by univariate and multivariate Cox-regression model analyses.
The median OS was 21.7 months (95% CI 18.3 - 25.1) in the TACE + sorafenib group and 11.5 months (95% CI 7.8, 15.2) in the TACE group. The median TTP was 10.2 (95% CI 9.7-10.7) and 6.7 (95% CI 6.1, 7.2) months in the TACE + sorafenib and TACE groups, respectively. Patients receiving the combination therapy had a higher survival rate (p < 0.032) and longer average interval to TACE (p < 0.001), but lower progression rate (p < 0.001) as compared to those treated with TACE. Multivariate analysis revealed that the combination therapy, BCLC stage, and the absence of progression were all associated with improved OS (p ≤ 0.009) while the treatment, BCLC stage, and AFP levels were significantly associated with TTP (all p ≤ 0.021). The majority of AEs identified in patients receiving the combination therapy were classified as Grades 1 and 2, all grade AE showed skin related reaction (including hand-foot skin reaction (58%) and rash (20%)), and fatigue (52%) being the most common.
Thus, sorafenib delivered concurrently with TACE provides survival benefits over TACE monotherapy, and these benefits may be related to a prolonged interval between subsequent TACE courses.
Clinical trial identification
All authors have declared no conflicts of interest.