Budget Impact Analysis of afatinib for first-line treatment of Non-Small Cell Lung Cancer (NSCLC) patients with uncommon EGFR mutations





Afatinib, Budget Impact, NSCLC, Osimertinib, Uncommon mutation


Background: The current clinical practice for patients affected by Non-Small Cell Lung Cancer (NSCLC) with uncommon mutation is based on afatinib and osimertinib, second and third generation of Tyrosine Kinase Inhibitor (TKI) respectively. For uncommon EGFR mutations, it is still unclear which EGFR TKI is most effective, since there are few dedicated prospective studies and Next Generation Sequencing (NGS) techniques trace an increasingly large and sometimes little-known population of EGFR mutations.

Objective: To determine the economic impact associated to afatinib and osimertinib, a Budget Impact model considering a 3-year time horizon with two scenarios was developed: a first scenario, called AS IS, based on treatment with afatinib and osimertinib according to a distribution of market shares as emerged from clinical practice; a second suitable scenario, called TO BE, based on reviewed literature data, assuming for each year a 10%, 15% and 20% increase in afatinib use, respectively.

Methods: Budget Impact analysis was conducted using a dynamic cohort model, in which the annual number of patients with NSCLC and uncommon mutations was equally distributed over 12 months. Progression-free survival (PFS) data for afatinib and osimertinib were extrapolated up to 36 months from published Kaplan Meier curves, and then the number of patients was estimated for each treatment.

Results: The increase of 10% in afatinib use allowed a saving of drug acquisition costs for the Italian NHS, over the 3-year time horizon, of –€ 622,432. The univariate sensitivity analysis shows the market share of osimertinib to be the parameter significantly affecting the results achieved in the base case.

Conclusions: The potential increase in the use of afatinib in patients with NSCLC and uncommon mutations leads to lower drug acquisition costs, lower Budget Impact and a saving of money for the Italian NHS.


Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. https://doi.org/10.3322/caac.21262 PMID:25651787 DOI: https://doi.org/10.3322/caac.21262

AIOM, Airtum. I numeri del cancro in Italia 2020. https://www.aiom.it/wp-content/uploads/2020/10/2020_Numeri_Cancro-operatori_web.pdf

Cancer.net. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics. (accessed October 2021)

Travis WD, Brambilla E, Noguchi M, et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013;137(5):668-684. https://doi.org/10.5858/arpa.2012-0263-RA PMID:22970842 DOI: https://doi.org/10.5858/arpa.2012-0263-RA

Travis WD, Brambilla E, Noguchi M, et al. Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013;137(5):685-705. https://doi.org/10.5858/arpa.2012-0264-RA PMID:22913371 DOI: https://doi.org/10.5858/arpa.2012-0264-RA

Goldstraw P, Chansky K, Crowley J, et al; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39-51. https://doi.org/10.1016/j.jtho.2015.09.009 PMID:26762738 DOI: https://doi.org/10.1016/j.jtho.2015.09.009

Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003;123(1)(suppl):21S-49S. https://doi.org/10.1378/chest.123.1_suppl.21S PMID:12527563 DOI: https://doi.org/10.1378/chest.123.1_suppl.21S

Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5)(suppl):e1S-e29S. https://doi.org/10.1378/chest.12-2345 PMID:23649439 DOI: https://doi.org/10.1378/chest.12-2345

Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446-454. https://doi.org/10.1038/nature25183 PMID:29364287 DOI: https://doi.org/10.1038/nature25183

Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23(25):5900-5909. https://doi.org/10.1200/JCO.2005.02.857 PMID:16043828 DOI: https://doi.org/10.1200/JCO.2005.02.857

Gristina V, Malapelle U, Galvano A, et al. The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal. Cancer Treat Rev. 2020;85:101994. https://doi.org/10.1016/j.ctrv.2020.101994PMID:32113081 DOI: https://doi.org/10.1016/j.ctrv.2020.101994

Masood A, Kancha RK, Subramanian J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: focus on afatinib. Semin Oncol. 2019;46(3):271-283. https://doi.org/10.1053/j.seminoncol.2019.08.004PMID:31558282 DOI: https://doi.org/10.1053/j.seminoncol.2019.08.004

Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019;94(8):1623-1640. https://doi.org/10.1016/j.mayocp.2019.01.013 PMID:31378236 DOI: https://doi.org/10.1016/j.mayocp.2019.01.013

Evans M, O’Sullivan B, Smith M, et al. Large-Scale EGFR Mutation Testing in Clinical Practice: Analysis of a Series of 18,920 Non-Small Cell Lung Cancer Cases. Pathol Oncol Res. 2019;25(4):1401-1409. https://doi.org/10.1007/s12253-018-0460-2 PMID:30094734 DOI: https://doi.org/10.1007/s12253-018-0460-2

Yang JC, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015;16(7):830-838. https://doi.org/10.1016/S1470-2045(15)00026-1 PMID:26051236 DOI: https://doi.org/10.1016/S1470-2045(15)00026-1

Passaro A, Mok T, Peters S, Popat S, Ahn MJ, de Marinis F. Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations. J Thorac Oncol. 2021;16(5):764-773. https://doi.org/10.1016/j.jtho.2020.12.002 PMID:33333327 DOI: https://doi.org/10.1016/j.jtho.2020.12.002

Cho JH, Lim SH, An HJ, et al. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020;38(5):488-495. https://doi.org/10.1200/JCO.19.00931PMID:31825714 DOI: https://doi.org/10.1200/JCO.19.00931

Bar J, Kian W, Wolner M, et al. 1206P UNcommon EGFR mutations: International Case series on efficacy of Osimertinib in Real-life practice in first-liNe setting (UNICORN) Annals of Oncology (2021) 32 (suppl_5): S961-S962 https://doi.org/10.1016/j.annonc.2021.08.1811 DOI: https://doi.org/10.1016/j.annonc.2021.08.1811

European Respiratory Society (ERS), The economic burden of lung disease in European Lung white book. https://www.erswhitebook.org/chapters/the-economic-burden-of-lung-disease. (Accessed October 2021)

Migliorino MR, Santo A, Romano G, et al. Economic burden of patients affected by non-small cell lung cancer (NSCLC): the LIFE study. J Cancer Res Clin Oncol. 2017;143(5):783-791. https://doi.org/10.1007/s00432-016-2326-x PMID:28215027 DOI: https://doi.org/10.1007/s00432-016-2326-x

AIOM.Linee guida neoplasia del polmone. Edizione 2020. https://www.aiom.it/wp-content/uploads/2020/10/2020_LG_AIOM_Polmone.pdf. (Accessed October 2020)

Rohatgi A. WebPlotDigitizer, Version 4.5. https://automeris.io/WebPlotDigitizer.

Baio G. survHE: Survival Analysis for Health Economic Evaluation and Cost-Effectiveness Modeling. J Stat Softw. 2020;95(14):1-47. https://doi.org/10.18637/jss.v095.i14 DOI: https://doi.org/10.18637/jss.v095.i14

Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12(1):9. https://doi.org/10.1186/1471-2288-12-9 PMID:22297116 DOI: https://doi.org/10.1186/1471-2288-12-9

Gideon E. Schwarz, Estimating the dimension of a model. Ann Stat. 1978;6(2):461-464. DOI: https://doi.org/10.1214/aos/1176344136

Andreano A, Peake MD, Janes SM, et al. The Care and Outcomes of Older Persons with Lung Cancer in England and the United States, 2008-2012. J Thorac Oncol. 2018;13(7):904-914. https://doi.org/10.1016/j.jtho.2018.04.022 PMID:29727739 DOI: https://doi.org/10.1016/j.jtho.2018.04.022

Gobbini E, Galetta D, Tiseo M, et al; other Co-Authors. Molecular profiling in Italian patients with advanced non-small-cell lung cancer: an observational prospective study. Lung Cancer. 2017;111:30-37. https://doi.org/10.1016/j.lungcan.2017.06.009 PMID:28838394 DOI: https://doi.org/10.1016/j.lungcan.2017.06.009

Park K, Tan EH, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17(5):577-589. https://doi.org/10.1016/S1470-2045(16)30033-X PMID:27083334 DOI: https://doi.org/10.1016/S1470-2045(16)30033-X

Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. https://doi.org/10.1056/NEJMoa1713137 PMID:29151359 DOI: https://doi.org/10.1056/NEJMe1714580

Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. https://doi.org/10.1016/S1470-2045(17)30608-3 PMID:28958502 DOI: https://doi.org/10.1016/S1470-2045(17)30608-3

Yang JC, Schuler M, Popat S, et al. Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases. J Thorac Oncol. 2020;15(5):803-815. https://doi.org/10.1016/j.jtho.2019.12.126 PMID:31931137 DOI: https://doi.org/10.1016/j.jtho.2019.12.126

Zöchbauer-Müller S, Kaserer B, Prosch H, et al. Case Report: Afatinib Treatment in a Patient With NSCLC Harboring a Rare EGFR Exon 20 Mutation. Front Oncol. 2021;10:593852. https://doi.org/10.3389/fonc.2020.593852 PMID:33575211 DOI: https://doi.org/10.3389/fonc.2020.593852

Additional Files



How to Cite

Pompilio G, Morabito A, Cortinovis DL, Integlia D. Budget Impact Analysis of afatinib for first-line treatment of Non-Small Cell Lung Cancer (NSCLC) patients with uncommon EGFR mutations. Grhta [Internet]. 2022 Jan. 31 [cited 2022 May 20];9(1):22-9. Available from: https://journals.aboutscience.eu/index.php/grhta/article/view/2351



Original Research Article