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Transarterial Chemoembolization within First 3 Months of Sorafenib Initiation Improves Overall Survival in Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study with Propensity Matching.

ABSTRACT: PURPOSE:The impact of transarterial chemoembolization after initiation of sorafenib (SOR) has not been prospectively compared with SOR alone in unresectable hepatocellular carcinoma (HCC). The objective of this study was to assess whether SOR + transarterial chemoembolization provides benefit over SOR alone in this setting. MATERIALS AND METHODS:A retrospective cohort study with propensity matching using data from patients prescribed SOR for HCC at Veterans Health Administration hospitals from 2007 to 2015. The primary outcome was overall survival from the time of SOR prescription and stratified by receipt of transarterial chemoembolization within 90 days of SOR initiation. RESULTS:A total of 4,896 patients received SOR for HCC, of whom 232 (4.7%) underwent transarterial chemoembolization within 90 days. Patients receiving transarterial chemoembolization + SOR were highly selected, being younger and with less significant hepatic dysfunction, earlier Barcelona Clinic Liver Cancer stage (P < .0001), and fewer tumors with lower rates of macrovascular invasion (MVI) and metastases (all P < .0001) than SOR-alone patients. In unadjusted analysis, SOR + transarterial chemoembolization was associated with reduced mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.53-0.71; P < .0001). After propensity matching, SOR + transarterial chemoembolization continued to show significant associations with reduced mortality with HR 0.75 (95% CI 0.62-0.92; P = .0005). Subgroup analysis suggests that the addition of transarterial chemoembolization to SOR improves outcomes in most patients, particularly those with Model for End-Stage Liver Disease score <15, platelets >50,000/?L, and >3 tumors with or without macrovascular invasion, without local invasion or metastases. CONCLUSIONS:Patients with unresectable HCC started on systemic therapy with SOR appear to benefit from adjuvant transarterial chemoembolization. Optimal application of multimodal therapy in this setting should be prospectively investigated.

SUBMITTER: Kaplan DE

PROVIDER: S-EPMC6104514 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Transarterial Chemoembolization within First 3 Months of Sorafenib Initiation Improves Overall Survival in Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study with Propensity Matching.

Kaplan David E DE Mehta Rajni R D'Addeo Kathryn K Gade Terence P TP Taddei Tamar H TH

Journal of vascular and interventional radiology : JVIR 20180222 4

<h4>Purpose</h4>The impact of transarterial chemoembolization after initiation of sorafenib (SOR) has not been prospectively compared with SOR alone in unresectable hepatocellular carcinoma (HCC). The objective of this study was to assess whether SOR + transarterial chemoembolization provides benefit over SOR alone in this setting.<h4>Materials and methods</h4>A retrospective cohort study with propensity matching using data from patients prescribed SOR for HCC at Veterans Health Administration h ...[more]

PMID: 29477619

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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.

Project description:BackgroundSorafenib and transarterial chemoembolization (TACE) might both provide survival benefit for advanced hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. We aimed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC.MethodsA Markov model was constructed in a hypothetical cohort of patients aged 60 years with advanced HCC and Child-Pugh A/B cirrhosis over a 2-year time frame. Three strategies (full or dose-adjusted sorafenib and TACE) were compared in two cost settings: China and the USA. Transition probabilities, utility and costs were extracted from systematic review of 27 articles. Sensitivity analysis and Monte Carlo analysis were conducted.ResultsFull and dose-adjusted sorafenib respectively produced 0.435 and 0.482 quality-adjusted life years (QALYs) while TACE produced 0.375 QALYs. The incremental cost-effectiveness ratio (ICER) of full-dose sorafenib versus TACE was $101,028.83/QALY in China whereas full-dose sorafenib is a dominant strategy (ICER of -$1,014,507.20/ QALY) compared with TACE in the USA. Compared to full-dose sorafenib, dose-adjusted sorafenib was the dominant strategy with the negative ICERs in both China (-$132,238.94/QALY) and the USA (-$230,058.09/QALY). However, dose-adjusted sorafenib is not available currently, so full-dose sorafenib should be compared with TACE. As the acceptability curves shown, full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries. Specifically, full-dose sorafenib was the cost-effective treatment compared with TACE if a WTP was set above $21,670 in the USA, whereas in China, TACE could be more favorable than full-dose sorafenib if a WTP was set below $10,473.ConclusionsDose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients. However, when confining the comparisons between full-dose sorafenib and TACE, full-dose sorafenib was cost-effective for these patients, under the accepted thresholds of WTP.

Dataset Information

Transarterial Chemoembolization within First 3 Months of Sorafenib Initiation Improves Overall Survival in Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study with Propensity Matching.

Publications

Transarterial Chemoembolization within First 3 Months of Sorafenib Initiation Improves Overall Survival in Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study with Propensity Matching.

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