Efficacy evaluation of the combination therapy of sorafenib and transarterial chemoembolization for unresectable HCC: a systematic review and meta-analysis of comparative studies

Background: Sorafenib and transarterial chemoembolization (TACE) are the standard treatments recommended by guidelines for unresectable hepatocellular carcinoma (HCC). Although previous studies have shown the combination therapy of sorafenib and TACE to be safe, there is no consensus regarding its efficacy. This systematic review and meta-analysis, which was based on the findings of comparative clinical trials, was conducted to provide up-to-date and comprehensive information about the efficacy of combination therapy versus TACE monotherapy in unresectable HCC. Methods: Multiple databases were systematically reviewed to screen studies through particular inclusion criteria. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was collected and analyzed by Revman 5.3 in a fixed or random effects meta-analysis model. Adverse events (AEs) were also evaluated. Results: This review ultimately included 14 comparative studies focused on combination therapy versus TACE monotherapy. Of these: 5 studies conducted TACE plus sorafenib versus TACE with placebo; 9 studies provided overall survival (OS) in combination groups which ranged from 10.3 to 29.7 months; and 10 studies provided time to progression (TTP) in combination groups which ranged from 2.6 to 10.8 months. The disease control rate (DCR) in combination groups ranged from 9.7% to 89.2% in 7 of the studies. After performing a random effects meta-analysis model, our study showed that OS (HR=0.65, 95% CI: 0.54-0.79, P<0.0001) and TTP (HR=0.72, 95% CI: 0.59-0.88, P=0.001) have been significantly improved in the combination therapy group when compared with the TACE monotherapy group. AEs mainly included hand-foot skin reaction (HFSR), fatigue and diarrhea and the majority of these were in grade 1 or grade 2. Conclusions: Combination therapy has significant advantages over TACE monotherapy in terms of improving TTP and OS.