Economic Analysis of Exclusionary EGFR Test Versus Up-Front NGS for Lung Adenocarcinoma in High EGFR Mutation Prevalence Areas

Authors: Szu-Chun Yang MD, PhD1, Yi-Chen Yeh MD2,3, Yi-Lin Chen MS4,5, and Chao-Hua Chiu MD3,6
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  • 1 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan;
  • | 2 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei;
  • | 3 College of Medicine, National Yang Ming Chiao Tung University, Taipei;
  • | 4 Molecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan;
  • | 5 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan; and
  • | 6 Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: This study sought to determine whether exclusionary EGFR mutation testing followed by next-generation sequencing (NGS) is a cost-efficient and timely strategy in areas with high prevalence rates of EGFR mutation. Methods: We developed a decision tree model to compare exclusionary EGFR testing followed by NGS and up-front NGS. Patients entered the model upon diagnosis of metastatic lung adenocarcinoma. Gene alterations with FDA-approved targeted therapies included EGFR, ALK, ROS1, BRAF, RET, MET, NTRK, and KRAS. Model outcomes were testing-related costs; time-to-test results; monetary loss, taking both costs and time into consideration; and percentage of patients who could be treated by FDA-approved therapies. Stacked 1-way and 3-way sensitivity analyses were performed. Results: Exclusionary EGFR testing incurred testing-related costs of US $1,387 per patient, a savings of US $1,091 compared with the costs of up-front NGS. The time-to-test results for exclusionary EGFR testing and up-front NGS were 13.0 and 13.6 days, respectively. Exclusionary EGFR testing resulted in a savings of US $1,116 in terms of net monetary loss, without a reduction of patients identified with FDA-approved therapies. The EGFR mutation rate and NGS cost had the greatest impact on minimizing monetary loss. Given that the tissue-based NGS turnaround time was shortened to 7 days, up-front NGS testing would become the best strategy if its price could be reduced to US $568 in Taiwan. Conclusions: In areas with high prevalence rates of EGFR mutation, exclusionary EGFR testing followed by NGS, rather than up-front NGS, is currently a cost-efficient strategy for metastatic lung adenocarcinoma.

Submitted August 4, 2021; final revision received December 8, 2021; accepted for publication December 8, 2021. Published online April 6, 2022.

Author contributions: Study design: Chiu. Data curation: Yeh, Chen. Model development and data analysis: Yang. Data interpretation: Yang, Chiu. Funding acquisition: Yang, Chiu. Investigation: Yang, Chiu. Project administration: Chiu. Manuscript preparation: All authors.

Disclosures: Dr. Chiu has disclosed receiving honoraria from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, and Takeda, and serving on the advisory board for Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and Roche. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by Taipei Veterans General Hospital (V110C-106) and the Ministry of Science and Technology (110-2314-B-006-100-MY2).

Correspondence: Chao-Hua Chiu, MD, Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan. Email: jhchiou@vghtpe.gov.tw

Supplementary Materials

    • Supplemental Materials (PDF 906 KB)
  • 1.

    Dagogo-Jack I, Azzolli CG, Fintelmann F, et al. Clinical utility of rapid EGFR genotyping in advanced lung cancer [published online July 24, 2018]. JCO Precis Oncol, doi.org/10.1200/PO.17.00299

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Dagogo-Jack I, Robinson H, Mino-Kenudson M, et al. Expediting comprehensive molecular analysis to optimize initial treatment of lung cancer patients with minimal smoking history. J Thorac Oncol 2019;14:835843.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Ettinger DS, Wood DE, Aisner DL, et al. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 2.2021. Accessed February 25, 2021. To view the most recent version, visit NCCN.org

    • Search Google Scholar
    • Export Citation
  • 4.

    Kohno T, Nakaoku T, Tsuta K, et al. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res 2015;4:156164.

  • 5.

    Pennell NA, Mutebi A, Zhou ZY, et al. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non-small-cell lung cancer using a decision analytic model. JCO Precis Oncol 2019;3:19.

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

    Rolfo C, Mack PC, Scagliotti GV, et al. Liquid biopsy for advanced non-small cell lung cancer (NSCLC): a statement paper from the IASLC. J Thorac Oncol 2018;13:12481268.

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

    National Health Insurance Administration. National Health Insurance medical service payment items and standards [in Mandarin]. Accessed December 13, 2021. Available at: https://www.nhi.gov.tw/Content_List.aspx?n=58ED9C8D8417D00B

    • Search Google Scholar
    • Export Citation
  • 8.

    Guardant360 CDx. How do you treat at the speed of cancer? The answers are in our blood. Accessed November 1, 2021. Available at: https://guardant360cdx.com

    • Search Google Scholar
    • Export Citation
  • 9.

    National Statistics, R.O.C. (Taiwan). Monthly income of major job for employees [in Mandarin]. Accessed December 13, 2021. Available at: https://www.stat.gov.tw/ct.asp?xItem=46590&ctNode=3579&mp=4

    • Search Google Scholar
    • Export Citation
  • 10.

    Hsu KH, Ho CC, Hsia TC, et al. Identification of five driver gene mutations in patients with treatment-naïve lung adenocarcinoma in Taiwan. PLoS One 2015;10:e0120852.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Wu YC, Chang IC, Wang CL, et al. Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in 312 non-small cell lung cancer patients in Taiwan. PLoS One 2013;8:e70839.

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

    Chen YF, Hsieh MS, Wu SG, et al. Clinical and the prognostic characteristics of lung adenocarcinoma patients with ROS1 fusion in comparison with other driver mutations in East Asian populations. J Thorac Oncol 2014;9:11711179.

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

    Wu SG, Liu YN, Yu CJ, et al. Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion. Genes Chromosomes Cancer 2018;57:513521.

  • 14.

    Gow CH, Hsieh MS, Wu SG, et al. A comprehensive analysis of clinical outcomes in lung cancer patients harboring a MET exon 14 skipping mutation compared to other driver mutations in an East Asian population. Lung Cancer 2017;103:8289.

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

    Okamura R, Boichard A, Kato S, et al. Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics [published online November 15, 2018]. JCO Precis Oncol, doi.org/10.1200/PO.18.00183

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Wu SG, Liao WY, Su KY, et al. Prognostic characteristics and immunotherapy response of patients with nonsquamous NSCLC with KRAS mutation in East Asian populations: a single-center cohort study in Taiwan. JTO Clin Res Rep 2020;2:100140.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Gow CH, Chang HT, Lim CK, et al. Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas. Genes Chromosomes Cancer 2017;56:373381.

  • 18.

    Roche Diagnostics. cobas EGFR Mutation Test v2. Accessed January 21, 2022. Available at: https://diagnostics.roche.com/us/en/products/params/cobas-egfr-mutation-test-v2.html

    • Search Google Scholar
    • Export Citation
  • 19.

    Shen CI, Chiang CL, Luo YH, et al. The intrinsic limitation and clinical impact of mutant allele-specific real-time PCR-based EGFR mutation assay in NSCLC. J Thorac Oncol 2021;16:S966.

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

    Goswami RS, Luthra R, Singh RR, et al. Identification of factors affecting the success of next-generation sequencing testing in solid tumors. Am J Clin Pathol 2016;145:222237.

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

    Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res 2019;25:46914700.

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

    Drummond MF, Sculpher MJ, Claxton K, et al. Methods for the Economic Evaluation of Health Care Programmes. Oxford, UK: Oxford University Press; 2015.

    • Search Google Scholar
    • Export Citation
  • 23.

    Centers for Medicare & Medicaid Services. Clinical laboratory fee schedule files. Accessed November 1, 2021. Available at: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/Clinical-Laboratory-Fee-Schedule-Files

    • Search Google Scholar
    • Export Citation
  • 24.

    Yu TM, Morrison C, Gold EJ, et al. Budget impact of next-generation sequencing for molecular assessment of advanced non-small cell lung cancer. Value Health 2018;21:12781285.

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

    U.S. Bureau of Labor Statistics. Occupational employment and wage statistics. Accessed November 1, 2021. Available at: https://www.bls.gov/oes/2020/may/oes_nat.htm

    • Search Google Scholar
    • Export Citation
  • 26.

    Calvayrac O, Pradines A, Pons E, et al. Molecular biomarkers for lung adenocarcinoma. Eur Respir J 2017;49:1601734.

  • 27.

    Loong H, Wong CKH, Leung LKS, et al. Economic impact of next-generation sequencing (NGS) versus single-gene testing modalities to detect genomic alterations (GAs) in metastatic non-small cell lung cancer (mNSCLC) in Asia. Ann Oncol 2020;31(Suppl 6):S13941395.

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

    Tan AC, Lai GGY, Tan GS, et al. Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: incremental yield of actionable alterations and cost-effectiveness analysis. Lung Cancer 2020;139:207215.

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

    Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 2015;5:28922911.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Esteban E, Majem M, Martinez Aguillo M, et al. Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: the Spanish REASON study. Cancer Epidemiol 2015;39:291297.

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

    Signorovitch J, Zhou Z, Ryan J, et al. Budget impact analysis of comprehensive genomic profiling in patients with advanced non-small cell lung cancer. J Med Econ 2019;22:140150.

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

    Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol 2018;36:25322537.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Tsurutani J, Iwata H, Krop I, et al. Targeting HER2 with trastuzumab deruxtecan: a dose-expansion, phase I study in multiple advanced solid tumors. Cancer Discov 2020;10:688701.

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

    Prelaj A, Bottiglieri A, Proto C, et al. Poziotinib for EGFR and HER2 exon 20 insertion mutation in advanced NSCLC: results from the expanded access program. Eur J Cancer 2021;149:235248.

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

    Schluckebier L, Caetano R, Garay OU, et al. Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients. BMC Cancer 2020;20:875.

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

    Yang SC, Lai CH, Kuo CW, et al. Downstream complications and healthcare expenditure after invasive procedures for lung lesions in Taiwan. Int J Environ Res Public Health 2021;18:4040.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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