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Real-World Patient Characteristics, Treatment Patterns, and Mutation Testing Patterns Among US Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations

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Abstract

Introduction

Approximately 15% of patients with non-small cell lung cancer (NSCLC) harbor an epidermal growth factor receptor mutation (EGFRm). Mutation testing (including EGFRm) is recommended for patients with advanced NSCLC (aNSCLC) prior to initiating first-line therapy (L1) or after progression on targeted therapy. To elucidate current and future unmet needs, the present study characterized real-world EGFR testing patterns and treatment patterns in patients with aNSCLC.

Methods

This retrospective observational cohort study evaluated newly diagnosed adult patients with aNSCLC (stage IIIB or higher) from the Flatiron Health database. Eligible patients received at least L1 during 2015–2020 (testing cohorts) or 2011–2020 (treatment cohorts). Eligible patients for the treatment cohorts had an EGFR mutation.

Results

The testing cohort included 22,726 patients, 75.5% had at least one EGFR test and 15.2% of those tested were positive for EGFR mutation. From 2015 to 2020, the median time from sample collection to test results decreased substantially while the proportion of NGS EGFR tests and use of plasma samples increased. The treatment cohort included 3701 patients (95% common mutations [cEGFR], 5.0% exon 20 insertions [ex20ins]). Three or more lines of therapy (LOTs) were observed in approximately 30% of patients. For L1, most cEGFR patients received EGFR tyrosine kinase inhibitors (EGFR-TKI, 68.1%) or platinum-based chemotherapy (PBC, 24.8%); most ex20ins patients received PBC (66.1%) or EGFR-TKI (17.5%). The most common L2 was EGFR-TKI (54.1%) or PBC (22.8%) for cEGFR and immunotherapy (25.9%) or PBC (25.9%) for ex20ins. No predominant L3 was evident in either group.

Conclusion

This real-world study, among the largest analyses of testing patterns for patients with aNSCLC, demonstrates a comprehensive view of treatment patterns for patients with EGFR mutations, including ex20ins. Despite recent improvement, increased use of EGFR testing, including advanced methods, is needed to optimize treatment pathways and outcomes. Additionally, the lack of a predominant therapy in later lines indicates a need for new therapies.

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References

  1. Rebuzzi SE, Zullo L, Rossi G, et al. Novel emerging molecular targets in non-small cell lung cancer. Int J Mol Sci. 2021;22:5. https://doi.org/10.3390/ijms22052625.

  2. Yuan M, Huang L-L, Chen J-H, Wu J, Xu Q. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019;4:61. https://doi.org/10.1038/s41392-019-0099-9.

  3. American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022.

  4. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–40. https://doi.org/10.1016/j.mayocp.2019.01.013.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang Z, Yang S, Ma Y, et al. Consistency of recommendations for the diagnosis and treatment of non-small cell lung cancer: a systematic review. Transl Lung Cancer Res. 2021;10(6):2715–32.

    Article  Google Scholar 

  6. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60. https://doi.org/10.1097/jto.0000000000000630.

  7. Kalemkerian G, Narula N, Kennedy E, et al. Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018;36(9):911–9. https://doi.org/10.1200/JCO.2017.76.7293.

    Article  CAS  PubMed  Google Scholar 

  8. Ettinger DS, Wood DE, Aggarwal C, et al. NCCN guidelines insights: non-small cell lung cancer, version 1.2020. J Natl Compr Canc Netw. 2019;17(12):1464–72. https://doi.org/10.6004/jnccn.2019.0059.

    Article  CAS  PubMed  Google Scholar 

  9. Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther. 2019;4:5. https://doi.org/10.1038/s41392-019-0038-9.

  10. Janning M, Süptitz J, Albers-Leischner C, et al. Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM). Ann Oncol. 2022. https://doi.org/10.1016/j.annonc.2022.02.225.

    Article  PubMed  Google Scholar 

  11. Dong RF, Zhu ML, Liu MM, et al. EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: from molecular mechanisms to clinical research. Pharmacol Res. 2021;167:105583. https://doi.org/10.1016/j.phrs.2021.105583.

  12. Bauml JM VS, Minchom A, et al. Underdiagnosis of EGFR Exon 20 insertion mutation variants: estimates from NGS-based real-world datasets. In: Presentation #3399. World Conference on Lung Cancer; 2020.

  13. He C, Wei C, Wen J, et al. Comprehensive analysis of NGS and ARMS-PCR for detecting EGFR mutations based on 4467 cases of NSCLC patients. J Cancer Res Clin Oncol. 2021. https://doi.org/10.1007/s00432-021-03818-w.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Revelo AE, Martin A, Velasquez R, et al. Liquid biopsy for lung cancers: an update on recent developments. Ann Transl Med. 2019;7(15):349. https://doi.org/10.21037/atm.2019.03.28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zatarain-Barrón ZL, Cardona AF, Díaz-García D, et al. Cell-free circulating tumor DNA improves standard genotyping of non-small-cell lung cancer and increases detection of targetable alterations in a selected hispanic cohort. Oncology. 2021;99(8):539–46. https://doi.org/10.1159/000514648.

  16. Bustamante Alvarez JG, Janse S, et al. Treatment of non-small-cell lung cancer based on circulating cell-free DNA and impact of variation allele frequency. Clin Lung Cancer. 2021;22(4):e519–27. https://doi.org/10.1016/j.cllc.2020.11.007.

  17. Parums DV. Editorial: Global regulatory initiatives deliver accelerated approval of the first bispecific therapeutic monoclonal antibody for advanced non-small cell lung cancer (NSCLC). Med Sci Monit. 2021;27:e934854. https://doi.org/10.12659/MSM.934854.

  18. Flatiron. 2020. https://flatiron.com/about-us/. Accessed 1 Dec 2020.

  19. Winfree KB, Molife C, Peterson PM, et al. Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations. Future Oncol. 2021;17(22):2867–81.

    Article  CAS  Google Scholar 

  20. John A, Yang B, Shah R. Clinical impact of adherence to NCCN guidelines for biomarker testing and first-line treatment in advanced non-small cell lung cancer (aNSCLC) using real-world electronic health record data. Adv Ther. 2021;38(3):1552–66. https://doi.org/10.1007/s12325-020-01617-2.

  21. Chelabi S, Mignard X, Leroy K, et al. EGFR exon 20 insertion in metastatic non-small-cell lung cancer: survival and clinical efficacy of EGFR tyrosine-kinase inhibitor and chemotherapy. Cancers (Basel). 2021;13:20.

    Article  Google Scholar 

  22. Chouaid C, Filleron T, Debieuvre D, et al. A real-world study of patients with advanced non-squamous non-small cell lung cancer with EGFR exon 20 insertion: clinical characteristics and outcomes. Target Oncol. 2021;16(6):801–11. https://doi.org/10.1007/s11523-021-00848-9.

    Article  PubMed  Google Scholar 

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Acknowledgements

Funding

This research, and payment of the journal’s Rapid Service Fees, was funded by Janssen Scientific Affairs, LLC, USA.

Medical Writing, Editorial, and Other Assistance

The authors thank Lorie Ellis for helpful comments on the manuscript. Shayan Ghosh, Mu Sigma Business Solutions Pvt. Ltd., Bengaluru, India, provided data programming support. Leo J. Philip Tharappel and Manasi Date, SIRO Clinpharm, Mumbai, India, provided editorial assistance.

Author Contributions

All authors were involved in study design, analysis and interpretation. JH was responsible for the statistical analyses. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors provided direction and comments on the manuscript, made the final decision about where to publish these data, and approved submission to this journal.

Disclosures

All authors are employees of Janssen Scientific Affairs, LLC (a Johnson & Johnson company) and hold stock in Johnson & Johnson.

Prior Presentation

Posters presented at ASCO-Quality Care Symposium, September, 2021 and AMCP Nexus, October, 2021.

Compliance with Ethics Guidelines

This study was exempt from review by an institutional review board as the database was compliant with the Health Insurance Portability and Accountability Act, the data did not include any identifiable patient information, and the study did not involve human subjects, as defined by 45 CFR 46.102(f)(2).

Data Availability

The data that support the findings of this study have been originated by Flatiron Health, Inc. These de-identified data are subject to a license agreement with Flatiron Health; interested researchers should contact DataAccess@flatiron.com to determine licensing terms.

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Authors and Affiliations

  1. Janssen Scientific Affairs, LLC, Titusville, NJ, USA

    Jinghua He, Christopher D. Pericone & Julie Vanderpoel

Authors
  1. Jinghua He
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  2. Christopher D. Pericone
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  3. Julie Vanderpoel
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Corresponding author

Correspondence to Julie Vanderpoel.

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He, J., Pericone, C.D. & Vanderpoel, J. Real-World Patient Characteristics, Treatment Patterns, and Mutation Testing Patterns Among US Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations. Adv Ther 39, 3347–3360 (2022). https://doi.org/10.1007/s12325-022-02189-z

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