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PharmacoEconomics
Erschienen in: PharmacoEconomics 11/2015

01.11.2015 | Original Research Article

Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany

verfasst von: Katharina Schremser, Wolf H. Rogowski, Sigrid Adler-Reichel, Amanda L. H. Tufman, Rudolf M. Huber, Björn Stollenwerk

Erschienen in: PharmacoEconomics | Ausgabe 11/2015

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Abstract

Background

Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC).

Objective

The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance.

Methods

A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses.

Results

The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of €200, yielding an incremental cost-effectiveness ratio (ICER) of €15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about €58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds.

Limitations

The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients.

Conclusions

Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.
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Literatur
1.
Kaatsch P, Spix C, Hentsche S, Katalinic A, Luttmann S, Stegmaier C, et al. Krebs in Deutschland 2009/2010. 8th ed. Berlin: Robert Koch Institut; 2013.
2.
Blum T, Schicke B, Schönfeld N, Jagota A. Versorgungssituation beim Lungenkarzinom in Deutschland—Ergebnisse einer Auswertung bundesweiter Daten klinischer Krebsregister. 54th Annual Meeting of the German Association for Medical Informatics, Biometry and Epidemiology (GMDS). Essen, Germany. 2014.
3.
Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn: JMD. 2013;15(4):415–53.CrossRefPubMed
4.
Goeckenjan G, Sitter H, Thomas M, Branscheid D, Flentje M, Griesinger F, et al. Prevention, diagnosis, therapy, and follow-up of lung cancer. Interdisciplinary guideline of the German Respiratory Society and the German Cancer Society—abridged version. Pneumologie. 2011;65(8):e51–75.CrossRefPubMed
5.
Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol: Off J Eur Soc Med Oncol/ESMO. 2012;23 Suppl 7:vii56–64.
6.
Liang W, Wu X, Fang W, Zhao Y, Yang Y, Hu Z, et al. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations. PLoS One. 2014;9(2):e85245.PubMedCentralCrossRefPubMed
7.
Popat S, Mok T, Yang JC, Wu YL, Lungershausen J, Stammberger U, et al. Afatinib in the treatment of EGFR mutation-positive NSCLC—a network meta-analysis. Lung Cancer (Amst, Neth). 2014;85(2):230–8.CrossRef
8.
Sebastian M, Schmittel A, Reck M. First-line treatment of EGFR-mutated non-small cell lung cancer: critical review on study methodology. Eur Respir Rev. 2014;23(131):92–105.CrossRefPubMed
9.
Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol. 2006;11(3):190–8.CrossRefPubMed
10.
Gahr S, Stoehr R, Geissinger E, Ficker JH, Brueckl WM, Gschwendtner A, et al. EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer. 2013;109(7):1821–8.PubMedCentralCrossRefPubMed
11.
Hatz MH, Schremser K, Rogowski WH. Is individualized medicine more cost-effective? A systematic review. Pharmacoeconomics 2014;32:443–455.CrossRefPubMed
12.
Lange A, Prenzler A, Frank M, Golpon H, Welte T, von der Schulenburg JM. A systematic review of the cost-effectiveness of targeted therapies for metastatic non-small cell lung cancer (NSCLC). BMC Pulm Med. 2014;14:192.PubMedCentralCrossRefPubMed
13.
de Lima Lopes G Jr, Segel JE, Tan DS, Do YK, Mok T, Finkelstein EA. Cost-effectiveness of epidermal growth factor receptor mutation testing and first-line treatment with gefitinib for patients with advanced adenocarcinoma of the lung. Cancer. 2012;118(4):1032–9.CrossRefPubMed
14.
Carlson JJ, Garrison LP, Ramsey SD, Veenstra DL. The potential clinical and economic outcomes of pharmacogenomic approaches to EGFR-tyrosine kinase inhibitor therapy in non-small-cell lung cancer. Value Health: J Int Soc Pharmacoecon Outcomes Res. 2009;12(1):20–7.CrossRef
15.
Handorf EA, McElligott S, Vachani A, Langer CJ, Bristol Demeter M, Armstrong K, et al. Cost effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung. J Oncol Pract/Am Soc Clin Oncol. 2012;8(5):267–74.CrossRef
16.
Luengo-Fernandez R, Leal J, Gray A, Sullivan R. Economic burden of cancer across the European Union: a population-based cost analysis. Lancet Oncol. 2013;14(12):1165–74.CrossRefPubMed
17.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRefPubMed
18.
19.
Warth A, Penzel R, Brandt R, Sers C, Fischer JR, Thomas M, et al. Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies. Virchows Arch: Int J Pathol. 2012;460(4):407–14.CrossRef
20.
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;12:9.PubMedCentralCrossRefPubMed
21.
Latimer NR. Survival analysis for economic evaluations alongside clinical trials—extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med Decis Mak: Int J Soc Med Decis Mak. 2013;33(6):743–54.CrossRef
22.
Asukai Y, Valladares A, Camps C, Wood E, Taipale K, Arellano J, et al. Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population. BMC Cancer. 2010;10:26.PubMedCentralCrossRefPubMed
23.
Nafees B, Stafford M, Gavriel S, Bhalla S, Watkins J. Health state utilities for non small cell lung cancer. Health Quality Life Outcomes. 2008;6:84.CrossRef
24.
Lloyd A, van Hanswijck de Jonge P, Doyle S, Cornes P. Health state utility scores for cancer-related anemia through societal and patient valuations. Value Health: J Int Soc Pharmacoecon Outcomes Res. 2008;11(7):1178–85.CrossRef
25.
Shabaruddin FH, Chen LC, Elliott RA, Payne K. A systematic review of utility values for chemotherapy-related adverse events. Pharmacoeconomics. 2013;31(4):277–88.CrossRefPubMed
26.
Borget I, Cadranel J, Pignon JP, Quoix E, Coudert B, Westeel V, et al. Cost-effectiveness of three strategies for second-line erlotinib initiation in nonsmall-cell lung cancer: the ERMETIC study part 3. Eur Respir J. 2012;39(1):172–9.CrossRefPubMed
27.
Schnabel PA, Smit E, Carpeno Jde C, Lesniewski-Kmak K, Aerts J, Kraaij K, et al. Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting: baseline results of an observational study (FRAME). Lung Cancer (Amst, Neth). 2012;78(3):263–9.CrossRef
28.
Kiss N, Isenring E, Gough K, Krishnasamy M. The prevalence of weight loss during (chemo)radiotherapy treatment for lung cancer and associated patient- and treatment-related factors. Clin Nutr (Edinburgh, Scotland). 2014;33(6):1074–80.CrossRef
29.
Federal Statistical Office. Mikrozensus 2009—Fragen der Gesundheit—Körpermaße der Bevölkerung. 2011.
30.
31.
32.
33.
Bock JO, Brettschneider C, Seidl H, Bowles D, Holle R, Greiner W, et al. Calculation of standardised unit costs from a societal perspective for health economic evaluation. Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)). 2015;77(1):53–61.
34.
Liu X, Lu Y, Zhu G, Lei Y, Zheng L, Qin H, et al. The diagnostic accuracy of pleural effusion and plasma samples versus tumour tissue for detection of EGFR mutation in patients with advanced non-small cell lung cancer: comparison of methodologies. J Clin Pathol. 2013;66(12):1065–9.PubMedCentralCrossRefPubMed
35.
Iyer S, Taylor-Stokes G, Roughley A. Symptom burden and quality of life in advanced non-small cell lung cancer patients in France and Germany. Lung Cancer (Amst, Neth). 2013;81(2):288–93.CrossRef
36.
Brown T, Pilkington G, Bagust A, Boland A, Oyee J, Tudur-Smith C, et al. Clinical effectiveness and cost-effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer: a systematic review and economic evaluation. Health Technol Assess (Winch, Engl). 2013;17(31):1–278.
37.
Zhu J, Li T, Wang X, Ye M, Cai J, Xu Y, et al. Gene-guided gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive non-small cell lung cancer: an economic analysis. BMC Cancer. 2013;13:39.PubMedCentralCrossRefPubMed
38.
Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2):121–8.CrossRefPubMed
39.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–8.CrossRefPubMed
40.
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.CrossRefPubMed
41.
Han JY, Park K, Kim SW, Lee DH, Kim HY, Kim HT, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol: Off J Am Soc Clin Oncol. 2012;30(10):1122–8.CrossRef
42.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.CrossRefPubMed
43.
Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213–22.CrossRefPubMed
44.
Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31(27):3327–34.CrossRef
45.
Caro JJ, Nord E, Siebert U, McGuire A, McGregor M, Henry D, et al. The efficiency frontier approach to economic evaluation of health-care interventions. Health Econ. 2010;19(10):1117–27.CrossRefPubMed
46.
McCabe C, Claxton K, Culyer AJ. The NICE cost-effectiveness threshold: what it is and what that means. Pharmacoeconomics. 2008;26(9):733–44.CrossRefPubMed
47.
Federal Statistical Office. Volkswirtschaftliche Gesamtrechnungen. Fachserie 18 Reihe 1.5. 2015.
48.
Marseille E, Larson B, Kazi DS, Kahn JG, Rosen S. Thresholds for the cost-effectiveness of interventions: alternative approaches. Bull World Health Org. 2015;93(2):118–24.PubMedCentralCrossRefPubMed
49.
Eberhardt W, Thomas M, Graf von Schulenburg J, Dietel M, Schirmacher P, Gutendorf B, et al. EGFR mutation testing and first-line treatment of patients with advanced NSCLC and positive EGFR mutation status—results from a German registry (#9144). Eur J Cancer (Oxf, Engl: 1990). 2011;47 Suppl. 1:S636.CrossRef
50.
Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155(3):137–44.PubMedCentralCrossRefPubMed
51.
Facciolongo N, Patelli M, Gasparini S, Lazzari Agli L, Salio M, Simonassi C, et al. Incidence of complications in bronchoscopy. Multicentre prospective study of 20,986 bronchoscopies. Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace/Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Universita di Napoli, Secondo ateneo. 2009;71(1):8–14.
52.
Metadaten
Titel
Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany
verfasst von
Katharina Schremser
Wolf H. Rogowski
Sigrid Adler-Reichel
Amanda L. H. Tufman
Rudolf M. Huber
Björn Stollenwerk
Publikationsdatum
01.11.2015
Verlag
Springer International Publishing
Erschienen in
PharmacoEconomics / Ausgabe 11/2015
Print ISSN: 1170-7690
Elektronische ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-015-0305-8

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