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Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

ABSTRACT: BACKGROUND:Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE. METHODS:Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center. RESULTS:No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple-drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single-drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple-drug chemotherapy benefit versus single-drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller). CONCLUSIONS:Triple-drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single-drug TACE.

SUBMITTER: He M

PROVIDER: S-EPMC6675716 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

He MinKe M Li Qing Q Shen JingXian J Tan GuoSheng G Li QiJiong Q Lai JiaYing J Wei Wei W Zhang YaoJun Y Zou RuHai R Chen MinShan M Guo RongPing R Shi Ming M

Cancer medicine 20190617 9

<h4>Background</h4>Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE.<h4>Methods</h4>Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobapl ...[more]

PMID: 31207163

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Project description:Transarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naïve tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE. TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p<0.0001). In addition, multivariable Cox model demonstrates that TACE Navigator was independently associated with survival (HR: 9.31, 95% CI: 3.46-25.0, p<0.001). In our validation cohorts, the association between TACE Navigator and survival remained robust in both Asian patients who received adjuvant TACE (Hong Kong: 60 months vs 25.6 months p=0.007; Shandong: 61.3 months vs 32.1 months, p=0.027) and European patients who received TACE as primary therapy (Mainz: 60 months vs 41.5 months, p=0.041). These results indicate that a TACE-specific molecular classifier is robust in predicting TACE response. This gene signature can be used to identify patients who will have the greatest survival benefit after TACE treatment and enable personalized treatment modalities for patients with HCC.

Project description:BackgroundThe combination of tyrosine kinase inhibitors (TKIs) and transarterial chemoembolization (TACE) fulfills an important role in the treatment of unresectable hepatocellular carcinoma (uHCC). Among the combination therapies, both lenvatinib and sorafenib combined with TACE are recommended as first-¬line treatments for uHCC. However, at present, limited data are available concerning the efficacy and safety of these two combination therapies in uHCC.MethodsA detailed systematic search for studies on lenvatinib plus TACE (LEN+TACE) and sorafenib plus TACE (SOR+TACE) was conducted in the online databases PubMed, Embase and The Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), time to progression (TTP), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.ResultsOne randomized controlled trial and five cohort studies with 598 patients (LEN+TACE: 261, SOR+TACE: 337) were included in the meta-analysis. A higher rate of odds ratio (OR) for the objective response rate (ORR) [OR: 3.63; 95% confidence intervals (95% CI): 1.89-6.95; I squared statistic (I2) = 57%, P < 0.001] and disease control rate (DCR) (OR: 3.78; 95% CI: 2.00-7.16; I2 = 52%, P = 0.0001) were observed in the LEN+SOR group compared with the SOR+TACE group. The LEN+TACE group also had significant longer OS [hazard ratio (HR): 0.67; 95% CI: 0.52-0.85; I2 = 1%, P = 0.001], PFS (HR: 0.49; 95% CI: 0.38-0.62; I2 = 0%, P? 0.001) and TTP (HR: 0.62; 95% CI: 0.45-0.84; I2 = 0%, P = 0.002) compared with the SOR+TACE group. The incidence of hypertension (OR: 3.05; 95% CI: 1.45-6.39; P = 0.003) and proteinuria (OR: 5.25; 95% CI: 1.73-15.89; P = 0.003) were significantly higher in the LEN+TACE group than SOR+TACE group, while LEN+TACE group exhibited a lower rate of hand-foot-skin reaction (HFSR) (OR: 0.51; 95% CI: 0.27-0.95; P = 0.03) compared with the SOR+TACE group.ConclusionThe combination therapy of LEN+TACE showed significant superiority compared with SOR+TACE in terms of its efficacy for patients with uHCC. SOR+TACE should be recommended as a replacement therapy when serious AEs occur during the administration of LEN+TACE as the combination therapy.

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.

Dataset Information

Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

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Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

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