Skip to main content
Top
Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Hepatocellular Carcinoma | Research article

Comparative cost-effectiveness of cabozantinib as second-line therapy for patients with advanced hepatocellular carcinoma in Germany and the United States

Authors: Maximilian Sieg, Michael Hartmann, Utz Settmacher, Habibollah Arefian

Published in: BMC Gastroenterology | Issue 1/2020

Login to get access

Abstract

Background

Cabozantinib was approved by the European Medicines Agency and the Federal Drug Administration as an option for sorafenib-resistant advanced hepatocellular carcinoma, increasing overall survival and progression-free survival compared with placebo. We evaluated the cost-effectiveness of cabozantinib in the second-line setting for patients with an advanced hepatocellular carcinoma from the German statutory health insurance perspective compared with an US scenario using US prices.

Methods

A Markov model was developed to compare the costs and effectiveness of cabozantinib with best supportive care in the second-line treatment of advanced hepatocellular carcinoma over a lifetime horizon. Health outcomes were measured in discounted life years and discounted quality-adjusted life years. Survival probabilities were estimated using parametric survival distributions based on CELESTIAL trial data. Utilities were derived from the literature. Costs contained drugs, monitoring and adverse events measured in US Dollars. Model robustness was addressed in univariable, scenario and probabilistic sensitivity analyses.

Results

Cabozantinib generated a gain of 0.18 life years (0.15 quality-adjusted life years) compared with best supportive care. The total mean cost per patient was $56,621 for cabozantinib and $2064 for best supportive care in the German model resulting in incremental cost-effectiveness ratios for cabozantinib of $306,778/life year and $375,470/quality-adjusted life year. Using US prices generated costs of $177,496 for cabozantinib and $4630 for best supportive care and incremental cost-effectiveness ratios of $972,049/life year and $1,189,706/quality-adjusted life year.

Conclusions

Our analysis established that assuming a willingness-to-pay threshold of $163,371/life year (quality-adjusted life year) for the German model and $188,559/life year (quality-adjusted life year) for the US model, cabozantinib is not cost-effective compared with best supportive care. Sensitivity analyses showed that cabozantinib was not cost-effective in almost all our scenarios.
Appendix
Available only for authorised users
Literature
1.
go back to reference Baecker A, Liu X, La Vecchia C, Zhang ZF. Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. Eur J Cancer Prev. 2018;27(3):205–12.PubMedPubMedCentralCrossRef Baecker A, Liu X, La Vecchia C, Zhang ZF. Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. Eur J Cancer Prev. 2018;27(3):205–12.PubMedPubMedCentralCrossRef
4.
go back to reference Malek NP, Schmidt S, Huber P, Manns MP, Greten TF. The diagnosis and treatment of hepatocellular carcinoma. Dtsch Arztebl Int. 2014;111(7):101–6.PubMedPubMedCentral Malek NP, Schmidt S, Huber P, Manns MP, Greten TF. The diagnosis and treatment of hepatocellular carcinoma. Dtsch Arztebl Int. 2014;111(7):101–6.PubMedPubMedCentral
5.
go back to reference Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol. 2013;31(28):3509–16.PubMedCrossRef Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol. 2013;31(28):3509–16.PubMedCrossRef
6.
go back to reference Zhu AX, Kudo M, Assenat E, Cattan S, Kang Y-K, Lim HY, et al. EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib. J Clin Oncol. 2014;32(3_suppl):172.CrossRef Zhu AX, Kudo M, Assenat E, Cattan S, Kang Y-K, Lim HY, et al. EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib. J Clin Oncol. 2014;32(3_suppl):172.CrossRef
7.
go back to reference Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66.PubMedCrossRef Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66.PubMedCrossRef
8.
go back to reference Hillienhof A. Regorafenib: Onkologen kritisieren Marktrücknahme. Dtsch Arztebl Int. 2016;797(131):17. Hillienhof A. Regorafenib: Onkologen kritisieren Marktrücknahme. Dtsch Arztebl Int. 2016;797(131):17.
9.
go back to reference IQWiG. Cabozantinib (hepatozelluläres Karzinom) – Nutzenbewertung gemäß § 35a SGB V – Dossierbewertung. 2019. Accessed 11 Feb 2020. IQWiG. Cabozantinib (hepatozelluläres Karzinom) – Nutzenbewertung gemäß § 35a SGB V – Dossierbewertung. 2019. Accessed 11 Feb 2020.
10.
go back to reference Abou-Alfa GK, Meyer T, Cheng A-L, El-Khoueiry AB, Rimassa L, Ryoo B-Y, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.PubMedCrossRef Abou-Alfa GK, Meyer T, Cheng A-L, El-Khoueiry AB, Rimassa L, Ryoo B-Y, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.PubMedCrossRef
12.
go back to reference Braithwaite RS, Meltzer DO, King JT Jr, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med Care. 2008;46(4):349–56.PubMedCrossRef Braithwaite RS, Meltzer DO, King JT Jr, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med Care. 2008;46(4):349–56.PubMedCrossRef
18.
go back to reference Ishak KJ, Kreif N, Benedict A, Muszbek N. Overview of parametric survival analysis for health-economic applications. Pharmacoeconomics. 2013;31(8):663–75.PubMedCrossRef Ishak KJ, Kreif N, Benedict A, Muszbek N. Overview of parametric survival analysis for health-economic applications. Pharmacoeconomics. 2013;31(8):663–75.PubMedCrossRef
19.
go back to reference Abou-Alfa GK, Mollon P, Meyer T, Cheng A-L, El-Khoueiry AB, Kelley RK, et al. Quality-adjusted life years assessment using cabozantinib for patients with advanced hepatocellular carcinoma (aHCC) in the CELESTIAL trial. J Clin Oncol. 2019;37(4_suppl):207.CrossRef Abou-Alfa GK, Mollon P, Meyer T, Cheng A-L, El-Khoueiry AB, Kelley RK, et al. Quality-adjusted life years assessment using cabozantinib for patients with advanced hepatocellular carcinoma (aHCC) in the CELESTIAL trial. J Clin Oncol. 2019;37(4_suppl):207.CrossRef
20.
go back to reference Thompson Coon J, Hoyle M, Green C, Liu Z, Welch K, Moxham T, et al. Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation. Health Technol Assess. 2010;14(2):1–184 iii-iv.PubMedCrossRef Thompson Coon J, Hoyle M, Green C, Liu Z, Welch K, Moxham T, et al. Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation. Health Technol Assess. 2010;14(2):1–184 iii-iv.PubMedCrossRef
22.
go back to reference Camma C, Cabibbo G, Petta S, Enea M, Iavarone M, Grieco A, et al. Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma. Hepatology. 2013;57(3):1046–54.PubMedCrossRef Camma C, Cabibbo G, Petta S, Enea M, Iavarone M, Grieco A, et al. Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma. Hepatology. 2013;57(3):1046–54.PubMedCrossRef
23.
go back to reference Bruix J, Merle P, Granito A, Huang YH, Bodoky G, Yokosuka O, et al. Efficacy, safety, and health-related quality of life (HRQoL) of regorafenib in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: Results of the international, double-blind phase 3 RESORCE trial. Ann Oncol. 2016;27:vi564. https://doi.org/10.1093/annonc/mdw435.19. Bruix J, Merle P, Granito A, Huang YH, Bodoky G, Yokosuka O, et al. Efficacy, safety, and health-related quality of life (HRQoL) of regorafenib in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: Results of the international, double-blind phase 3 RESORCE trial. Ann Oncol. 2016;27:vi564. https://​doi.​org/​10.​1093/​annonc/​mdw435.​19.
26.
go back to reference Tumeh JW, Moore SG, Shapiro R, Flowers CR. Practical approach for using Medicare data to estimate costs for cost-effectiveness analysis. Expert Rev Pharmacoecon Outcomes Res. 2005;5(2):153–62.PubMedCrossRef Tumeh JW, Moore SG, Shapiro R, Flowers CR. Practical approach for using Medicare data to estimate costs for cost-effectiveness analysis. Expert Rev Pharmacoecon Outcomes Res. 2005;5(2):153–62.PubMedCrossRef
29.
go back to reference Meng J, Lister J, Vataire AL, Casciano R, Dinet J. Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England. Clinicoecon Outcomes Res. 2018;10:243–50.PubMedPubMedCentralCrossRef Meng J, Lister J, Vataire AL, Casciano R, Dinet J. Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England. Clinicoecon Outcomes Res. 2018;10:243–50.PubMedPubMedCentralCrossRef
30.
go back to reference Kobayashi M, Kudo M, Izumi N, Kaneko S, Azuma M, Copher R, et al. Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan. J Gastroenterol. 2019;54(6):558–70.PubMedPubMedCentralCrossRef Kobayashi M, Kudo M, Izumi N, Kaneko S, Azuma M, Copher R, et al. Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan. J Gastroenterol. 2019;54(6):558–70.PubMedPubMedCentralCrossRef
31.
36.
go back to reference Shlomai A, Leshno M, Goldstein DA. Cabozantinib for patients with advanced hepatocellular carcinoma: a cost-effectiveness analysis. Ther Adv Gastroenterol. 2019;12:1756284819878304.CrossRef Shlomai A, Leshno M, Goldstein DA. Cabozantinib for patients with advanced hepatocellular carcinoma: a cost-effectiveness analysis. Ther Adv Gastroenterol. 2019;12:1756284819878304.CrossRef
37.
go back to reference Liao W, Huang J, Hutton D, Zhu G, Wu Q, Wen F, et al. Cost-effectiveness analysis of cabozantinib as second-line therapy in advanced hepatocellular carcinoma. Liver Int. 2019;39(12):2408–16.PubMedCrossRef Liao W, Huang J, Hutton D, Zhu G, Wu Q, Wen F, et al. Cost-effectiveness analysis of cabozantinib as second-line therapy in advanced hepatocellular carcinoma. Liver Int. 2019;39(12):2408–16.PubMedCrossRef
38.
go back to reference Soto-Perez-de-Celis E, Aguiar PN, Cordon ML, Chavarri-Guerra Y, Lopes GL. Cost-effectiveness of Cabozantinib in the second-line treatment of advanced hepatocellular carcinoma. J Natl Compr Cancer Netw. 2019;17(6):669–75.CrossRef Soto-Perez-de-Celis E, Aguiar PN, Cordon ML, Chavarri-Guerra Y, Lopes GL. Cost-effectiveness of Cabozantinib in the second-line treatment of advanced hepatocellular carcinoma. J Natl Compr Cancer Netw. 2019;17(6):669–75.CrossRef
43.
go back to reference Parikh ND, Singal AG, Hutton DW. Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma. Cancer. 2017;123(19):3725–31.PubMedCrossRef Parikh ND, Singal AG, Hutton DW. Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma. Cancer. 2017;123(19):3725–31.PubMedCrossRef
44.
go back to reference Shlomai A, Leshno M, Goldstein DA. Regorafenib treatment for patients with hepatocellular carcinoma who progressed on sorafenib-a cost-effectiveness analysis. PLoS One. 2018;13(11):e0207132.PubMedPubMedCentralCrossRef Shlomai A, Leshno M, Goldstein DA. Regorafenib treatment for patients with hepatocellular carcinoma who progressed on sorafenib-a cost-effectiveness analysis. PLoS One. 2018;13(11):e0207132.PubMedPubMedCentralCrossRef
46.
go back to reference Tappenden P, Carroll C, Hamilton J, Kaltenthaler E, Wong R, Wadsley J, et al. Cabozantinib and vandetanib for unresectable locally advanced or metastatic medullary thyroid cancer: a systematic review and economic model. Health Technol Assess. 2019;23(8):1–144.PubMedPubMedCentralCrossRef Tappenden P, Carroll C, Hamilton J, Kaltenthaler E, Wong R, Wadsley J, et al. Cabozantinib and vandetanib for unresectable locally advanced or metastatic medullary thyroid cancer: a systematic review and economic model. Health Technol Assess. 2019;23(8):1–144.PubMedPubMedCentralCrossRef
47.
go back to reference Lister J, Vataire A, Amzal B, Dinet J, Meng J, Karcher H, et al. Cost-effectiveness in England of Cabozantinib for patients with advanced renal cell carcinoma (ARCC) after failure of prior therapy. Value Health. 2017;20(9):A441.CrossRef Lister J, Vataire A, Amzal B, Dinet J, Meng J, Karcher H, et al. Cost-effectiveness in England of Cabozantinib for patients with advanced renal cell carcinoma (ARCC) after failure of prior therapy. Value Health. 2017;20(9):A441.CrossRef
48.
go back to reference Edwards SJ, Wakefield V, Cain P, Karner C, Kew K, Bacelar M, et al. Axitinib, cabozantinib, everolimus, nivolumab, sunitinib and best supportive care in previously treated renal cell carcinoma: a systematic review and economic evaluation. Health Technol Assess. 2018;22(6):1–278.PubMedPubMedCentralCrossRef Edwards SJ, Wakefield V, Cain P, Karner C, Kew K, Bacelar M, et al. Axitinib, cabozantinib, everolimus, nivolumab, sunitinib and best supportive care in previously treated renal cell carcinoma: a systematic review and economic evaluation. Health Technol Assess. 2018;22(6):1–278.PubMedPubMedCentralCrossRef
50.
go back to reference Deniz B, Ambavane A, Yang S, Altincatal A, Doan J, Rao S, et al. Treatment sequences for advanced renal cell carcinoma: a health economic assessment. PLoS One. 2019;14(8):e0215761.PubMedPubMedCentralCrossRef Deniz B, Ambavane A, Yang S, Altincatal A, Doan J, Rao S, et al. Treatment sequences for advanced renal cell carcinoma: a health economic assessment. PLoS One. 2019;14(8):e0215761.PubMedPubMedCentralCrossRef
52.
go back to reference Skentzou E, Meng J, Lister J, Gray L. Pcn94 - cost-effectiveness of Cabozantinib versus Sunitinib or Pazopanib as first-line treatment of patients with advanced renal cell carcinoma in the Uk. Value Health. 2018;21:S30.CrossRef Skentzou E, Meng J, Lister J, Gray L. Pcn94 - cost-effectiveness of Cabozantinib versus Sunitinib or Pazopanib as first-line treatment of patients with advanced renal cell carcinoma in the Uk. Value Health. 2018;21:S30.CrossRef
53.
go back to reference Goldstein DA, Ahmad BB, Chen Q, Ayer T, Howard DH, Lipscomb J, et al. Cost-effectiveness analysis of Regorafenib for metastatic colorectal Cancer. J Clin Oncol. 2015;33(32):3727–32.PubMedPubMedCentralCrossRef Goldstein DA, Ahmad BB, Chen Q, Ayer T, Howard DH, Lipscomb J, et al. Cost-effectiveness analysis of Regorafenib for metastatic colorectal Cancer. J Clin Oncol. 2015;33(32):3727–32.PubMedPubMedCentralCrossRef
54.
go back to reference Cho SK, Hay JW, Barzi A. Cost-effectiveness analysis of Regorafenib and TAS-102 in refractory metastatic colorectal Cancer in the United States. Clin Colorectal Cancer. 2018;17(4):e751–e61.PubMedCrossRef Cho SK, Hay JW, Barzi A. Cost-effectiveness analysis of Regorafenib and TAS-102 in refractory metastatic colorectal Cancer in the United States. Clin Colorectal Cancer. 2018;17(4):e751–e61.PubMedCrossRef
55.
go back to reference Lin JK, Lerman BJ, Barnes JI, Boursiquot BC, Tan YJ, Robinson AQL, et al. Cost effectiveness of chimeric antigen receptor T-cell therapy in relapsed or refractory pediatric B-cell acute lymphoblastic leukemia. J Clin Oncol. 2018;36(32):3192-202. Lin JK, Lerman BJ, Barnes JI, Boursiquot BC, Tan YJ, Robinson AQL, et al. Cost effectiveness of chimeric antigen receptor T-cell therapy in relapsed or refractory pediatric B-cell acute lymphoblastic leukemia. J Clin Oncol. 2018;36(32):3192-202.
Metadata
Title
Comparative cost-effectiveness of cabozantinib as second-line therapy for patients with advanced hepatocellular carcinoma in Germany and the United States
Authors
Maximilian Sieg
Michael Hartmann
Utz Settmacher
Habibollah Arefian
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01241-y

Other articles of this Issue 1/2020

BMC Gastroenterology 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.