Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma

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Background: Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. Patients and Methods: Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. Results: In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63–0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. Conclusions: At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.

Submitted August 29, 2018; accepted for publication January 16, 2019.Author contributions: Study concept: Soto-Perez-de-Celis, Aguiar, Cordón, Lopes. Data curation: Soto-Perez-de-Celis, Aguiar, Cordón. Formal analysis: Aguiar. Investigation: All authors. Methodology: Soto-Perez-de-Celis, Aguiar. Manuscript preparation: All authors. Critical revision: All authors.Disclosures: The authors have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.View associated contentCorrespondence: Gilberto de Lima Lopes Jr, MD, MBA, Sylvester Comprehensive Cancer Center, University of Miami, 1120 NW 14th Street, Suite 650J, Miami, FL 33135. Email: glopes@med.miami.edu
  • 1.

    Ferlay J, Soerjomataram I, Ervik M, . GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Available at: http://globocan.iarc.fr. Accessed August 12, 2018.

  • 2.

    Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301–1314.

  • 3.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30.

  • 4.

    Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma—an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 2006;23:1535–1547.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Marrero JA, Kulik LM, Sirlin CB, . Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723–750.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Llovet JM, Ricci S, Mazzaferro V, . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–390.

  • 7.

    Cheng AL, Kang YK, Chen Z, . Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25–34.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Bruix J, Qin S, Merle P, . Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;389:56–66.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Kudo M, Finn RS, Qin S, . Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018;391:1163–1173.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Abou-Alfa GK, Meyer T, Cheng AL, . Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:54–63.

  • 11.

    The ASCO Post. FDA accepts supplemental new drug application for cabozantinib in previously treated advanced hepatocellular carcinoma. Available at: http://www.ascopost.com/News/58887. Published May 30, 2018. Accessed August 12, 2018.

  • 12.

    Parikh ND, Marshall VD, Singal AG, . Survival and cost-effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: an analysis of the SEER-Medicare database. Hepatology 2017;65:122–133.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Parikh ND, Singal AG, Hutton DW. Cost-effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma. Cancer 2017;123:3725–3731.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Meng J, Lister J, Vataire AL, . 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;10:243–250.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Swinburn P, Lloyd A, Nathan P, . Elicitation of health state utilities in metastatic renal cell carcinoma. Curr Med Res Opin 2010;26:1091–1096.

  • 16.

    Memorial Sloan Kettering Cancer Center Drug Pricing Lab. Drug abacus methods. Available at: https://drugpricinglab.org/tools/drug-abacus/methods/. Accessed August 12, 2018.

  • 17.

    Medicare.gov. Medicare plan finder. Available at: https://www.medicare.gov/find-a-plan/questions/home.aspx. Accessed August 12, 2018.

  • 18.

    Carr BI, Carroll S, Muszbek N, . Economic evaluation of sorafenib in unresectable hepatocellular carcinoma. J Gastroenterol Hepatol 2010;25:1739–1746.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Hagiwara M, Borker R, Oster G. Economic burden of adverse events in patients with metastatic renal cell carcinoma. Clin Ther 2013;35:1955–1963.

  • 20.

    Borovicka JH, Calahan C, Gandhi M, . Economic burden of dermatologic adverse events induced by molecularly targeted cancer agents. Arch Dermatol 2011;147:1403–1409.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Ting J, Tien Ho P, Xiang P, . Cost-effectiveness and value of information of erlotinib, afatinib, and cisplatin-pemetrexed for first-line treatment of advanced EGFR mutation-positive non-small-cell lung cancer in the United States. Value Health 2015;18:774–782.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Elting LS, Shih YC. The economic burden of supportive care of cancer patients. Support Care Cancer 2004;12:219–226.

  • 23.

    Janke AT, McNaughton CD, Levy PD. Incidence and cost of hypertensive emergencies in United States emergency departments. Ann Emerg Med 2015;66(Suppl):S68.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    May P, Normand C, Cassel JB, . Economics of palliative care for hospitalized adults with serious illness: a meta-analysis. JAMA Intern Med 2018;178:820–829.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Yezefski T, Le D, Chen L, . Comparison of chemotherapy use, cost, and survival in patients with metastatic colorectal cancer in Western Washington and British Columbia [abstract]. J Clin Oncol 2018; 36(Suppl):Abstract LBA3579.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Qin S, Bai Y, Lim HY, . Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31:3501–3508.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Centers for Medicare & Medicaid Services. Medicare ASP drug pricing files. Available at: https://www.cms.gov/apps/ama/license.asp?file=/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/Downloads/2018-July-ASP-Pricing-File.zip. Accessed August 12, 2018.

  • 28.

    Zhu AX, Finn RS, Edeline J, . Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol 2018;19:940–952.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Centers for Medicare & Medicaid Services. Physician Fee Schedule. CY 2018 Physician Fee Schedule Final Rule. Available at: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/. Accessed August 12, 2018.

  • 30.

    Noone AM, Howlader N, Krapcho M, , eds. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2008. Accessed August 12, 2018.

  • 31.

    Rich NE, Hester C, Odewole M, . Racial and ethnic differences in presentation and outcomes of hepatocellular carcinoma. Clin Gastroenterol Hepatol 2018;17:551–559.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Sanoff HK, Chang Y, Lund JL, . Sorafenib effectiveness in advanced hepatocellular carcinoma. Oncologist 2016;21:1113–1120.

  • 33.

    Lee IC, Chen YT, Chao Y, . Determinants of survival after sorafenib failure in patients with BCLC-C hepatocellular carcinoma in real-world practice. Medicine (Baltimore) 2015;94:e688.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Gyawali B, Prasad V. Me too-drugs with limited benefits—the tale of regorafenib for HCC. Nat Rev Clin Oncol 2017;14:653–654.

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