Transarterial chemoembolization plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

BackgroundTransarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration.MethodsPubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated.ResultsTwenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR = 0.66, 95% CI 0.50–0.81, P = 0.002) rather than OS (HR = 0.63, 95% CI 0.55–0.71, P = 0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR = 2.93, 95% CI 1.59–5.41, P = 0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45–0.79, P = 0.002) in the Asian countries group, and 0.82 (95% CI 0.59–1.05, P = 0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48–0.75, P = 0.050) in the Asian countries group and was 0.88 (95% CI 0.56–1.20, P = 0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension.ConclusionsCombination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS.Electronic supplementary materialThe online version of this article (10.1186/s12876-018-0849-0) contains supplementary material, which is available to authorized users.

Treatment by Transarterial Chemoembolization and Sorafenib for Hepatocellular Carcinoma vs Advanced Hepatocellular Carcinoma in Bangladesh: A Real-life Situation

“…13 In Korea, a cohort of 63 HCC cases (stage I; 1, stage II; 17, stage III; 38, and stage IV; 7 cases) was treated and the actual 5-year survival rate was 57.0% and the median survival time was 60 months. 14 The prognosis of advanced HCC is extremely bad and it has been reported that these patients may survive some months even getting treatment with sorafenib. 15 The study presented here has shown that 33 out of 77 patients with advanced HCC died within 3 months and majority of them died within 1 month after therapy commencement.…”

Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions

“…Also, the disease control rate, defined as a combination of complete response rate, partial response rate, and stable disease rate, increased significantly in the combination therapy group (odds ratio [OR] ¼ 2.93, 95% CI :1.59-5.41, p ¼ 0.005). 78 The role of SIRT in advanced HCC remains undetermined in BCLC guidelines. 79 The SARAH trial failed to show superiority of SIRT to sorafenib, in 467 patients with BCLC Stage A to C, recurrent tumor ineligible for curative surgical therapy or tumors refractory to TACE, CP score A to B, and ECOG 0 to 1.…”

Hepatocellular Carcinoma: Combined Transarterial Chemoembolization and Ablation

“…5 Targeted chemotherapies such as sorafenib and regorafenib show modest effectiveness in the treatment of HCC. [6][7][8][9] One study reported that transarterial chemoembolization (TACE) combined with sorafenib significantly decreased the diameter of tumor-associated hepatic arteries and their branches when compared with TACE alone in the treatment of advanced-stage HCC. 8 Additionally, a meta-analysis of 27 studies found that sorafenib plus TACE was superior to TACE alone in terms of time to progression but not overall survival.…”

“…8 Additionally, a meta-analysis of 27 studies found that sorafenib plus TACE was superior to TACE alone in terms of time to progression but not overall survival. 9 For these reasons, TACE plus sorafenib is recommended, although its use is not widespread.…”