Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study

Abstract

Background: Sorafenib is the standard treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). However, the treatment outcome is not satisfactory. We retrospectively analyzed whether adding transarterial embolization/chemoembolization (TA(C)E)-based locoregional therapy to sorafenib can further improve treatment efficacy. Patients and Methods: We included 147 BCLC stage C HCC patients with Child-Turcotte-Pugh class A liver function and treated with sorafenib for analysis. Through propensity score matching, we divided patients into the combined treatment group (n = 63; patients received TA(C)E-based locoregional treatment and sorafenib) and the sorafenib monotherapy group (n = 63). We analyzed the effects of patients’ clinical and tumor-related factors on their overall survival (OS) and time to tumor progression. Results: The OS was better in the combined treatment group than in the sorafenib monotherapy group (419 vs. 223 days, p = 0.028). In the Cox regression model, combined treatment, a lower baseline α-fetoprotein (AFP) level < 400 ng/mL, tumors without main portal venous tumorous thrombosis, and age ≥60 years were identified as independent factors for OS. Subgroup analysis demonstrated that patients with a higher baseline AFP level > 400 ng/mL, age < 60 years, tumors with branched portal venous tumorous thrombosis only or without extrahepatic metastasis benefited the most from combined treatment. Conclusion: Combining TA(C)E-based locoregional treatment with sorafenib resulted in better OS in patients with BCLC stage C HCC compared with sorafenib alone. TA(C)E-based locoregional treatment can be an adjunctive treatment to sorafenib for patients with advanced HCC and a satisfactory liver functional reserve.

The combination therapy of transarterial chemoembolisation and sorafenib is the preferred palliative treatment for advanced hepatocellular carcinoma patients: a meta-analysis

“…Our result, that the OS of patients with advanced HCC treated with combination therapy was superior to that of those patients treated with sorafenib alone, maps to the conclusions of 4 retrospective studies [19,31,56,57] but is in contrast to a clinical trial by Zhang and colleagues in 2015 [43]. In this study, despite a numerically greater median OS in the combined-therapy group than in the sorafenib-alone group (7.3 months vs. 6.0 months), no difference was observed between the two groups (P = 0.924).…”

Adjuvant transarterial chemoembolization to sorafenib in unresectable hepatocellular carcinoma: A meta‐analysis

“…1). 15,16,22–28 Across the nine studies, there were a total of 3868 patients, of which 1181 patients were from the TACE plus sorafenib group and 2,687 patients were from the sorafenib group. The characteristics of each study are listed in Table 1.…”

“…Sorafenib is a multikinase inhibitor that could inhibit the proliferation of liver cancer cells. Its function of anti‐tumor angiogenesis could inhibit the synthesis of HIF‐1α protein and suppress the overexpression of VEGF induced by TACE 22,41,42 . As a tyrosine kinase inhibitor, sorafenib could also inhibit the receptors of VEGF and regulate the downstream cellular pathway 6 .…”

Transarterial chemoembolization combined with apatinib for treatment of advanced hepatocellular carcinoma: analysis of survival and prognostic factors

“…Although the results of sorafenib combined with TACE in the treatment of advanced HCC were not satisfactory, the combination of apatinib with TACE may provide a new method of combination therapy. Several retrospective studies compared sorafenib combined with TACE versus sorafenib alone for advanced HCC and found that combination therapy improved the patients' survival [14,15].…”

“…However, a recent phase III clinical trial showed that the addition of TACE to sorafenib failed to achieve significant survival benefit [6]. The reported median OS in sorafenib plus TACE group ranged between 12.8 and 17.3 months [6,[14][15][16]. In contrast, although the combination of apatinib with TACE was compared with TACE alone, the median OS of the combined treatment group was reported to be 11.9-22 months [17][18][19][20][21].…”