Clinical trials of combined molecular targeted therapy and locoregional therapy in hepatocellular carcinoma: Past, present, and future

Background: Sorafenib, a multikinase inhibitor that targets angiogenesis in hepatocellular carcinoma (HCC), has become a standard treatment for advanced-stage HCC and has shown survival benefits in recent clinical trials. Transarterial chemoembolization (TACE) and sorafenib are currently standard treatments for intermediate and advanced-stage HCC, respectively. Combined locoregional therapy, including TACE and molecular targeted therapies such as sorafenib, is an issue under active investigation in an attempt to improve the outcomes of patients with unresectable HCC. Summary: Various clinical trials of these combined strategies have been conducted; however, the designs of these studies are diverse in terms of treatment modalities and schedules; comparisons with controls, baseline tumor stages, and hepatic functional reserves; and outcome measures. Key Messages: This article reviews heterogeneity in the design of recent clinical trials of combined locoregional and molecular targeted therapies and briefly addresses future study directions.