Cost‐effectiveness analysis of antiviral therapy in patients with advanced hepatitis B virus‐related hepatocellular carcinoma treated with sorafenib

Zhang, Pengfei; Yu, Yang; Wen, Feng; Wheeler, John R. C.; Fu, Ping; Li, Qiu

doi:10.1111/jgh.13425

Cited by 16 publications

(10 citation statements)

References 30 publications

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“…These findings suggest that sorafenib resistance in HCC may be attributable to the compensatory effects in response to the activated PI3K/AKT signaling pathway. In addition, Zhang et al (2016b) further indicated that phosphorylation-activated FAK participates in the activation of the PI3K/AKT signaling pathway when sorafenib resistance occurred in HCC cells. FAK is an aberrantly highly expressed cytoplasmic protein tyrosine kinase that can facilitate the progression and metastasis of HCC (Chen et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Cyclovirobuxine D Exerts Anticancer Effects by Suppressing the EGFR-FAK-AKT/ERK1/2-Slug Signaling Pathway in Human Hepatocellular Carcinoma

Zhang

Chen

Lin

et al. 2020

DNA and Cell Biology

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Hepatocellular carcinoma (HCC), the sixth most common malignancy worldwide, is characterized by a dismal prognosis due to high recurrence and metastasis rates. Thus, the need for the development of novel chemotherapeutic drugs is urgent. Cyclovirobuxine D (CVB-D), a steroidal alkaloid extracted from Buxus microphylla that has been extensively used to relieve the symptoms of cardiovascular diseases, has shown promising antineoplastic effects in recent studies. However, the therapeutic effects and underlying mechanisms of CVB-D on HCC remain largely unelucidated. This study experimentally indicated that CVB-D can repress HCC cell proliferation by arresting the cell cycle in G2 phase and can facilitate apoptosis. In addition, the migratory and invasive capabilities of HCC cells were noticeably attenuated by a nonlethal dose of CVB-D, and this attenuation was correlated with the inhibition of epithelial-mesenchymal transition (EMT). Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing nude mice. Regarding the molecular mechanisms of CVB-D activity, decreased Slug expression was determined to be associated with the aforementioned anti-HCC functions of this extract, which might be regulated by epidermal growth factor receptor (EGFR) through the focal adhesion kinase (FAK)-associated PI3K/AKT and MEK/ERK1/2 signaling pathways. Collectively, our results revealed the suppressive effects of CVB-D on progressive behaviors of HCC, including proliferation, migration, invasion, and EMT, in addition to its outstanding proapoptotic effects, which were correlated with the inhibition of the EGFR-FAK-AKT/ERK1/2-Slug signaling pathway. These discoveries provide an experimental and theoretical foundation for the use of CVB-D as a promising candidate for HCC therapy.

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Section: Discussionmentioning

confidence: 99%

Cyclovirobuxine D Exerts Anticancer Effects by Suppressing the EGFR-FAK-AKT/ERK1/2-Slug Signaling Pathway in Human Hepatocellular Carcinoma

Zhang

Chen

Lin

et al. 2020

DNA and Cell Biology

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“…Costs for managing grade 3‐4 AEs weighted by frequency were calculated based on the use of amlodipine 5 mg daily for hypertension, Eucerin cream for hand–foot syndrome and atropine/diphenoxylate and loperamide for diarrhoea . These costs were sourced from published literature, the Red Book, the British National Formulary and Chinese national drug prices . All costs were converted to 2017 US dollars at exchange rate of 1USD = 0.7075GBP and 1USD = 6.8RMB .…”

Section: Methodsmentioning

confidence: 99%

Cost‐effectiveness analysis of cabozantinib as second‐line therapy in advanced hepatocellular carcinoma

Liao

Huang

Hutton

et al. 2019

Liver International

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Background: In the CELESTIAL trial for patients with advanced hepatocellular carcinoma (HCC), cabozantinib showed improved survival compared with placebo but comes at a price. We aimed to investigate the cost-effectiveness of cabozantinib for sorafenib-resistant HCC from the payer's perspective of the USA, UK and China. Methods:We developed Markov models to simulate the patients pre-treated with first-line sorafenib following the CELESTIAL trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated for the treatment with cabozantinib or best supportive care. The list price for drugs was acquired from the Red Book, the British National Formulary, West China hospital and reported literature. Adverse events, utilities weights, and transition likelihood between states were sourced from the published randomized phase III trial. A willing-to-pay threshold was set $150 000/QALY in the USA, $70 671/QALY (£50 000/QALY) in the UK and $26 481/QALY (3x GDP per capita) in China. Deterministic and probabilistic sensitivity analyses were developed to test the models' uncertainty. Results:In the base case, treatment with cabozantinib increased effectiveness by 0.13 QALYs, resulting in an ICER vs best supportive care of $833 497/QALY in the USA, $304 177/QALY in the UK and $156 437/QALY in China. The models were most sensitive to assumptions about transitions to progression with both cabozantinib and best supportive care, the utility associated with being progression free. These results were robust across a range of scenarios and sensitivity analyses, including deterministic and probabilistic analyses.Conclusions: Cabozantinib at its current cost would not be a cost-effective treatment option for patients with sorafenib-resistant HCC from the payer's perspective in the USA, UK or China. Substantial discounts are necessary to meet conventional costeffectiveness thresholds. K E Y W O R D S cabozantinib, cost-effective, hepatocellular carcinoma, incremental cost-effectiveness ratio, Markov model, second-line therapy S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Liao W, Huang J, Hutton D, et al. Cost-effectiveness analysis of cabozantinib as second-line therapy in advanced hepatocellular carcinoma. Liver Int.

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“…Utility coefficients were retrieved and an average value was derived for each health state in the model [27][28][29][30][31][32][33]. For the toxicity and complications that are transient, we assumed that there was a lower utility for TACE plus SBRT with a multiplier 0.9.…”

Section: Quality-of-life Estimatesmentioning

confidence: 99%

Cost-effectiveness analysis of transarterial chemoembolization combined with stereotactic body radiation therapy versus transarterial chemoembolization for inoperable hepatocellular carcinoma: A markov modelling study

Wang¹,

Gc²,

Zhang³

et al. 2020

Preprint

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Background Transarterial chemoembolization (TACE) and Stereotactic body radiation therapy (SBRT) might both provide survival benefits for inoperable hepatocellular carcinoma (HCC). Adopting combined therapy as a solution carries major cost and resource implications. We aimed to estimate the cost-effectiveness of TACE plus SBRT and TACE alone in inoperable HCC. Methods A Markov model was constructed in a hypothetical cohort of patients aged 60 years with inoperable HCC and Child-Pugh A/B cirrhosis over a lifetime frame. Two strategies (TACE plus SBRT and TACE) were compared. Transition probabilities, utility and costs were extracted from published literature. Incremental cost-effectiveness ratios (ICER) were measured. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings. Results TACE plus SBRT and TACE respectively produced 12.26 and 9.67 quality-adjusted life years (QALYs). The ICER of TACE plus SBRT versus TACE was $3,133/QALY. One-way sensitivity analysis revealed that the utility of TACE combined with SBRT progress survival, probability of death from progress survival in TACE, and the initial cost of TACE combined with SBRT were the most sensitive parameters. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of US$ 29,440 per QALY was 95% and 5% for TACE plus SBRT and TACE. Conclusions This study indicated that TACE plus SBRT is cost-effective compared to TACE for inoperable HCC patients at a willingness to pay threshold as defined by WHO guidelines in China.

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Cost‐effectiveness analysis of antiviral therapy in patients with advanced hepatitis B virus‐related hepatocellular carcinoma treated with sorafenib

Abstract: Based on the cost-effectiveness threshold ($20 301.00/QALY in China), addition of antiviral therapy to sorafenib is considered to be a cost-effective option compared with sorafenib monotherapy in patients with advanced HBV-related HCC in China from the patient's perspective.

Cited by 16 publications

References 30 publications

Cyclovirobuxine D Exerts Anticancer Effects by Suppressing the EGFR-FAK-AKT/ERK1/2-Slug Signaling Pathway in Human Hepatocellular Carcinoma

Cyclovirobuxine D Exerts Anticancer Effects by Suppressing the EGFR-FAK-AKT/ERK1/2-Slug Signaling Pathway in Human Hepatocellular Carcinoma

Cost‐effectiveness analysis of cabozantinib as second‐line therapy in advanced hepatocellular carcinoma

Cost-effectiveness analysis of transarterial chemoembolization combined with stereotactic body radiation therapy versus transarterial chemoembolization for inoperable hepatocellular carcinoma: A markov modelling study

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