The online version of this article (https://doi.org/10.1186/s12876-018-0849-0) contains supplementary material, which is available to authorized users.
Lin Li, Wenzhuo Zhao and Mengmeng Wang contributed equally to this work.
Transarterial 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.
PubMed, 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.
Twenty-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.
Combination 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.
Additional file 1: Table S1. Tumor response criteria, DCR, TTP and OS in 13 non-comparative studies. (DOCX 21 kb)12876_2018_849_MOESM1_ESM.docx
Additional file 2: Table S2. DCR in 5 comparative studies. (DOCX 19 kb)12876_2018_849_MOESM2_ESM.docx
Additional file 3: Figure S1. Forest plot of TTP outcome about the relationship between etiology and treatment outcome. (TIF 1710 kb)12876_2018_849_MOESM3_ESM.tif
Additional file 4: Figure S2. Forest plot of OS outcome about the relationship between etiology and treatment outcome. (TIF 1717 kb)12876_2018_849_MOESM4_ESM.tif
Additional file 5: Table S3. The AEs occurred during combination therapy in 13 non-comparative studies. (DOCX 21 kb)12876_2018_849_MOESM5_ESM.docx
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