Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective

Authors: Ranee Mehra MD 1 , Candice Yong PhD 2 , Brian Seal RPh, MBA, PhD 2 , Marjolijn van Keep MSc 3 , Angie Raad MSc 4 and Yiduo Zhang PhD 2
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  • 1 University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland;
  • 2 AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland;
  • 3 BresMed Netherlands, Utrecht, The Netherlands; and
  • 4 BresMed Health Solutions, Sheffield, United Kingdom.
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Background: Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC. Methods: A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (ClinicalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained. Results: In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of $55,285 and $61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure. Conclusions: In a US healthcare setting, durvalumab was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.

Submitted October 23, 2019; accepted for publication July 14, 2020.

Author contributions: Study design: Mehra, Yong, Seal, Zhang. Design and development of global model: van Keep. Adaptation of model to US settings: Raad. Data analyses: Raad. Data interpretation: Mehra, Yong, Seal, van Keep, Zhang. Manuscript preparation: All authors.

Disclosures: Dr. Mehra has disclosed that she receives grant/research support from Merck and Astra Zeneca, and consulting fees from Genentech and Bayer. Drs. Yong, Seal, and Zhang have disclosed that they are employed by and own stock in AstraZeneca. Ms. van Keep and Ms. Raad have disclosed that they are employed by BresMed (under contract with AstraZeneca).

Funding: The PACIFIC study (ClinicalTrials.gov identifier: NCT02125461; EudraCT identifier: 2014-000336-42) was funded by AstraZeneca. The cost-effectiveness analysis, preparation of the associated report, and medical writing support provided during the preparation of this article were all funded by AstraZeneca.

Disclaimer: AstraZeneca was involved in the PACIFIC study design; in the collection, analysis, and interpretation of data; in the design and validation of the cost-effectiveness analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. Data underlying the findings described in this article may be obtained in accordance with AstraZeneca’s data-sharing policy described at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Correspondence: Ranee Mehra, MD, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD 21201. Email: ranee.mehra@umm.edu

Supplementary Materials

    • Supplemental Materials (PDF 643.34 KB)
  • 1.

    WHO. Cancer. September 12, 2018. Accessed February 27, 2019. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer

  • 2.

    American Cancer Society. Key statistics for lung cancer. Accessed October 12, 2020. Available at: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html

  • 3.

    Cancer.Net. Lung cancer – non-small cell: statistics. Accessed October 12, 2020. Available at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics

  • 4.

    Chen VW, Ruiz BA, Hsieh MC, . Analysis of stage and clinical/prognostic factors for lung cancer from SEER registries: AJCC staging and collaborative stage data collection system. Cancer 2014;120(Suppl 23):37813792.

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

    Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol 2017;8:120.

  • 6.

    Ahn JS, Ahn YC, Kim JH, . Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol 2015;33:26602666.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Aupérin A, Le Péchoux C, Rolland E, . Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010;28:21812190.

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

    Bradley JD, Hu C, Komaki R, . Long-term results of RTOG 0617: a randomized phase 3 comparison of standard dose versus high dose conformal chemoradiation therapy +/− cetuximab for stage III NSCLC [abstract]. Int J Radiat Oncol Biol Phys 2017;99(Suppl 2):S105.

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

    Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252264.

  • 10.

    Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015;33:19741982.

  • 11.

    Stewart R, Morrow M, Hammond SA, . Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer Immunol Res 2015;3:10521062.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Antonia SJ, Villegas A, Daniel D, . Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 2018;379:23422350.

  • 13.

    Antonia SJ, Villegas A, Daniel D, . Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017;377:19191929.

  • 14.

    Durvalumab. Prescribing information. AstraZeneca; 2018. Accessed February 27, 2019. Available at: https://www.azpicentral.com/imfinzi/imfinzi.pdf#page=1

  • 15.

    Bironzo P, Di Maio M. A review of guidelines for lung cancer. J Thorac Dis 2018;10(Suppl 13):S15561563.

  • 16.

    Besette Z. Guideline updates: NCCN extensively updates guideline for NSCLC. Journal of Clinical Pathways, November 6, 2018. Accessed May 13, 2019. Available at: https://www.journalofclinicalpathways.com/news/nccn-extensively-updates-guideline-nsclc

  • 17.

    Ettinger GS, Wood DE, Aggarwal C, . NCCN Clinical Practice Guidelines in Oncology: Non–Small Cell Lung Cancer. Version 1.2020. Accessed May 15, 2019. To view the most recent version, visit NCCN.org

  • 18.

    Social Security Administration. Actuarial life table: 2015. Accessed February 27, 2019. Available at: https://www.ssa.gov/oact/STATS/table4c6.html

  • 19.

    Butts C, Socinski MA, Mitchell PL, . Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol 2014;15:5968.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Bradley JD, Paulus R, Komaki R, . Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 2015;16:187199.

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

    Herdman M, Gudex C, Lloyd A, . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:17271736.

  • 22.

    Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005;43:203220.

  • 23.

    van Hout B, Janssen MF, Feng YS, . Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets. Value Health 2012;15:708715.

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

    Centers for Medicare & Medicaid Services. 2018 ASP drug pricing files. Accessed February 27, 2019. Available at: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2018ASPFiles.html

  • 25.

    IBM Watson Health. IBM Micromedex RED BOOK. Accessed February 27, 2019. Available at: https://www.ibm.com/us-en/marketplace/micromedex-red-book

  • 26.

    U.S. Bureau of Labor Statistics. Consumer Price Index. Accessed February 27, 2019. Available at: https://www.bls.gov/cpi

  • 27.

    Witlox WJA, van Asselt ADI, Wolff R, . Durvalumab for the treatment of locally advanced, unresectable, stage III non-small cell lung cancer: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics 2020;38:317324.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Tsujino K, Kurata T, Yamamoto S, . Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature. J Thorac Oncol 2013;8:11811189.

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

    Adamson DM, Chang S, Hansen LG. White paper: health research data for the real world: the MarketScan databases. Accessed June 4, 2019. Available at: https://www.ibm.com/downloads/cas/6KNYVVQ2

  • 30.

    Sanders GD, Neumann PJ, Basu A, . Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA 2016;316:10931103.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med 2014;371:796797.

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

    Bae YH, Mullins CD. Do value thresholds for oncology drugs differ from nononcology drugs? J Manag Care Spec Pharm 2014;20:10861092.

  • 33.

    Institute for Clinical and Economic Review. Treatment options for advanced non-small cell lung cancer: effectiveness, value and value-based price benchmarks. Accessed June 24, 2019. Available at: https://icer.org/wp-content/uploads/2020/10/MWCEPAC_NSCLC_Final_Evidence_Report_Meeting_Summary_110116.pdf

    • Export Citation
  • 34.

    Criss SD, Mooradian MJ, Sheehan DF, . Cost-effectiveness and budgetary consequence analysis of durvalumab consolidation therapy vs no consolidation therapy after chemoradiotherapy in stage III non-small cell lung cancer in the context of the US health care system. JAMA Oncol 2019;5:358365.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Criss SD, Mooradian MJ, Kong CY. Changes to model assumptions of the cost-effectiveness of durvalumab therapy for non-small cell lung cancer—in reply. JAMA Oncol 2019;5:10661067.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Jørgensen J, Servos S, Kefalas P. The potential price and access implications of the cost-utility and budget impact methodologies applied by NICE in England and ICER in the US for a novel gene therapy in Parkinson’s disease. J Mark Access Health Policy 2018;6:1500419.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Mariotto AB, Yabroff KR, Shao Y, . Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst 2011;103:117128.

  • 38.

    Neumann PJ, Cohen JT. Measuring the value of prescription drugs. N Engl J Med 2015;373:25952597.

  • 39.

    Slomiany M, Madhavan P, Kuehn M, . Value frameworks in oncology: comparative analysis and implications to the pharmaceutical industry. Am Health Drug Benefits 2017;10:253260.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Schnipper LE, Davidson NE, Wollins DS, . Updating the American Society of Clinical Oncology value framework: revisions and reflections in response to comments received. J Clin Oncol 2016;34:29252934.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) with NCCN Evidence Blocks. Accessed April 21, 2020. Available at: https://www.nccn.org/evidenceblocks/default.aspx

  • 42.

    National Comprehensive Cancer Network. NCCN Framework for Resource Stratification of NCCN Guidelines (NCCN Framework). Accessed April 21, 2020. Available at: https://www.nccn.org/framework/

  • 43.

    Cherny NI, Sullivan R, Dafni U, . A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015;26:15471573.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Institute for Clinical and Economic Review. Overview of the ICER value assessment framework and update for 2017–2019. Accessed June 24, 2019. Available at: https://icer.org/wp-content/uploads/2020/10/ICER-value-assessment-framework-Updated-050818.pdf

  • 45.

    Memorial Sloan Kettering Cancer Center, Drug Pricing Laboratory. Drug Abacus. Accessed May 13, 2019. Available at: http://abacus.realendpoints.com/abacus-mskcc?ab-eff=1000&ab-tox=0.1&ab-nov=1&ab-rare=1&ab-pop=1&ab-dev=1&ab-prog=1.0&ab-need=1&ab-time=1607377695

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