Transarterial chemoembolization (TACE) plus sorafenib: a real winning combination?
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ABSTRACT:
SUBMITTER: Adhoute X
PROVIDER: S-EPMC7791214 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Transarterial chemoembolization (TACE) plus sorafenib: a real winning combination?
Adhoute Xavier X Anty Rodolphe R Bourlière Marc M
Annals of translational medicine 20201201 23
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Project description:BackgroundSorafenib is used in patients with intermediate or advanced stage hepatocellular carcinoma (HCC) before or after of transarterial chemoembolization (TACE). However, the survival outcomes of TACE combined with sorafenib versus TACE alone remain controversial. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC.MethodsPubmed and Embase databases were systematically reviewed for studies published up to November 2013, that compared TACE alone or in combination with sorafenib. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), time to progression (TTP), objective response rate (ORR), and progression free survival (PFS) using random-effects or fixed-effects model, depending on the heterogeneity between the included studies.ResultsSix studies published from 2011 to 2013, with a total of 1254 patients, were included in this meta-analysis. The pooled results showed that TACE combined with sorafenib significantly improved OS (HR = 0.65; 95% CI: 0.47-0.89, P = 0.007), TTP (HR = 0.68; 95% CI: 0.52-0.87, P = 0.003), ORR (HR = 1.06; 95% CI: 1.01-1.12, P = 0.021), but did not affect PFS (HR = 0.84; 95% CI: 0.62-1.14, P = 0.267). The incidence of grade III/IV adverse reaction was higher in the TACE plus sorafenib group than in the TACE group.ConclusionsThe meta-analysis confirmed that the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC, can improve the OS, TTP, and ORR. This combination therapy was also associated with a significantly increased risk of adverse reactions.
| S-EPMC4063775 | biostudies-literature
Project description: Not available
| S-EPMC7791245 | biostudies-literature
Project description:BackgroundSorafenib has been recommended as the first-line treatment and shown to prolong median overall survival (OS) of patients with advanced unresectable hepatocellular carcinoma (HCC). Recently, a growing amount of research has supported the application of transarterial chemoembolization (TACE) in patients with advanced-stage HCC. The aim of this study was to compare the outcomes of TACE and sorafenib and identify the prognostic factors related to OS for Barcelona Clinic Liver Cancer (BCLC) stage C patients with PS 1 but without vascular invasion or extrahepatic spread.MethodsA total of 323 consecutive patients in BCLC stage C with PS 1 but without vascular invasion or extrahepatic spread were enrolled in this retrospective study. Survival analyses were performed using the Kaplan-Meier analysis, and the statistical differences between the TACE and sorafenib groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsBased on the Kaplan-Meier curves, patients treated with TACE showed a better OS than those undergoing sorafenib, with respective OS at 1, 3, and 5 years (67.7%, 41.5%, 23.2% vs. 55.6%, 29.6%, 4.8%; log-rank P=0.002). The univariate analysis indicated that tumor size, tumor number, and treatment method, along with platelet (PLT), white blood cell (WBC), and α-fetoprotein (AFP) count, were associated with OS. The multivariate analysis demonstrated that tumor size, tumor number, and treatment method were significant prognostic factors for OS. According to the subgroups analyses based on the tumor size and tumor number, there were significant differences in OS among overall subsets between TACE and sorafenib therapy.ConclusionsTACE provided better prognostic performance than sorafenib and should be suggested as an alternative treatment modality to sorafenib for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread.
| S-EPMC7290559 | biostudies-literature
Project description:IntroductionSeveral clinical trials comparing the efficacy and safety of transarterial chemoembolization (TACE) plus molecular-targeted agents versus TACE alone revealed no clinical benefits in progression-free survival (PFS) or overall survival (OS). Here, we report the final OS analysis from the TACTICS trial, which previously demonstrated significant improvement in PFS with TACE plus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) (NCT01217034).MethodsPatients with unresectable HCC were randomized to a TACE plus sorafenib group (N = 80) or a TACE alone group (N = 76). Patients in the combination treatment group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable progression. In this trial, TACE-specific PFS was used. TACE-specific PFS is defined as the time from randomization to progressive disease (PD) or death from any cause, and PD was defined as untreatable progression, caused by the inability of a patient to further receive or benefit from TACE for reasons that include intrahepatic tumor progression (25% increase vs. baseline) according to response evaluation criteria in cancer of the liver, the detection of extrahepatic spread, vascular invasion, or transient deterioration of liver function to Child-Pugh C after TACE.ResultsAt the cut-off date of July 31, 2020, 131 OS events were observed. The median OS was 36.2 months with TACE plus sorafenib and 30.8 months with TACE alone (hazard ratio [HR] = 0.861; 95% confidence interval [CI], 0.607-1.223; p = 0.40, ΔOS, 5.4 months). The updated PFS was 22.8 months with TACE plus sorafenib and 13.5 months with TACE alone (HR = 0.661; 95% CI, 0.466-0.938; p = 0.02). Post-trial treatments with active procedures/agents were received by 47 (58.8%) patients in the TACE plus sorafenib group and 58 (76.3%) in the TACE alone group (p = 0.01). In post hoc analysis, PFS and OS benefit were shown in HCC patients with tumor burden beyond up-to-7 criteria.ConclusionsIn TACTICS trial, TACE plus sorafenib did not show significant OS benefit over TACE alone; however, clinical meaningful OS prolongation and significantly improved PFS was observed. Thus, the TACE plus sorafenib can be considered a choice of treatment in intermediate-stage HCC, especially in patients with high tumor burden. Trial Registration: NCT01217034.
| S-EPMC9294961 | biostudies-literature
Project description:BACKGROUND: Disease progression of hepatocellular cancer (HCC) in patients eligible for liver transplantation (LTx) occurs in up to 50% of patients, resulting in withdrawal from the LTx waiting list. Transarterial chemoembolization (TACE) is used as bridging therapy with highly variable response rates. The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer. DESIGN: The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety. DISCUSSION: As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.
| S-EPMC2630329 | biostudies-literature
Project description:BACKGROUND:Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets. METHODS:Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physician's discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected. RESULTS:In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade ?3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged. CONCLUSIONS:The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE.
| S-EPMC4789900 | biostudies-literature
Project description:ObjectivesTo develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib.MethodsThis retrospective multicenter study consisted of 201 patients with treatment-naïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction.ResultsThe median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023).ConclusionThe deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib.
| S-EPMC7556271 | biostudies-literature
Project description: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.
| S-EPMC6124009 | biostudies-literature
Project description:AimsThe purpose of the present study was to compare the efficacies of transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy for treating patients with advanced hepatocellular carcinoma (HCC).MethodsWe enrolled 321 patients and selected 280 with advanced HCC (Barcelona Clinic Liver Cancer stage C) who underwent TACE therapy between February 2009 and February 2013. TACE alone (monotherapy group) was administered to 198 patients (70.7%), and the remaining 82 (29.3%) underwent repeat combined TACE and sorafenib therapy (combined group). To minimize selection bias, these latter 82 patients were matched using propensity-score matching at a 1∶2 ratio with 164 patients who received TACE monotherapy. The primary endpoints were overall survival (OS) and related subgroup analysis. The secondary endpoints were time to progression (TTP) and treatment-related adverse events.ResultsOf the respective patients in the combined and monotherapy groups, 64.6% and 49.2% had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. In the propensity-score-matched cohort, the OS survival of the combined group was significantly higher compared with the monotherapy group (7.0 months vs. 4.9 months, respectively, P = 0.003). The TTP was significantly longer in the combined group (2.6 months vs. 1.9 months, respectively, P = 0.001). Subgroup analysis showed that the outcomes of patients with advanced HCC without main portal vein invasion who were treated with combined therapy were significantly better compared with those who received monotherapy (P<0.05). Univariate and subsequent multivariate analyses revealed that the addition of sorafenib was an independent predictor of favorable OS and TTP (adjusted hazard ratios, 0.63 and 0.62, respectively; P<0.05 for both).ConclusionSorafenib plus TACE was more effective than TACE monotherapy for treating patients with advanced HCC without main portal vein invasion. Future trials with larger samples are required to validate these preliminary findings.
| S-EPMC4016022 | biostudies-literature
Project description:BackgroundPatient selection for transarterial chemoembolization (TACE) has remained challenging. Currently used markers mainly reflect liver function and turned out as less reliable in larger clinical trials. The patients´ body composition has been linked with patient outcome in different cancers. Now, we analyzed the function of different parameters of the patient's body composition as prognostic and/ or predictive parameters in patients that received TACE.MethodsCT scans were used to assess five parameters of the individual body composition (skeletal muscle index (SMI), median muscular attenuation (MMA), bone mineral density (BMD) as well as the visceral and subcutaneous fat area) in 89 patients undergoing TACE. Results were correlated with tumor response to TACE and outcome of patients.ResultsSMI and visceral fat area were significantly higher in male patients and among patients undergoing TACE for HCC compared to patients with liver metastases. While all parameters of the body composition did not predict response to TACE, patients with an SMI below the ideal cutoff value of 37.76 cm2/m2 had a significantly reduced long-term outcome with a median overall survival of 404 days compared to 1321 days for patients with a high SMI. Moreover, the pre-interventional SMI turned out as an independent prognostic factor in a multivariate Cox regression model including clinicopathological parameters and laboratory markers of organ dysfunction and systemic inflammation (HR: 0.899, 95% CI 0.827-0.979, p = 0.014).ConclusionThe pre-interventional SMI represents an independent prognostic factor for overall survival following TACE. Assessment of the individual body composition using routine CT scan might help to identify the ideal patients for TACE.
| S-EPMC10356883 | biostudies-literature