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The Importance of Testing for EGFR Mutations at Initial Diagnosis in Metastatic NSCLC

Lung cancer and the role of epidermal growth factor receptor (EGFR)

Today, lung cancer is a leading cause of cancer deaths in the United States

An estimated 222,500 new cases of lung cancer were diagnosed in the US in 2017.1 The 2 main types of lung cancer are:

  • Non–small cell lung cancer (NSCLC), occurring in 85% of patients1
  • Small cell lung cancer (SCLC), occurring in 15% of patients1

This website focuses on NSCLC, since it is the most common form of lung cancer.

Infographic showing epidemiological statistics of NSCLC patients: 70% of patients with NSCLC will be diagnosed with locally advanced or metastatic lung cancer.

Infographic showing epidemiological statistics of NSCLC patients: The 5-year survival rate for metastatic or stage 4 NSCLC is ~1%.

Infographic showing 1 in 4 deaths from cancer are the result of lung cancer

Predictive biomarkers in NSCLC: An exciting discovery

The NSCLC treatment landscape is changing, and physicians are using biomarkers to help tailor and personalize therapy for their patients. Cancer biomarkers are substances in the body that can be identified or measured, and may be used to guide treatment decisions as well as predict how well a patient will respond to treatment.3 Some of the most common biomarkers in NSCLC are genetic changes, and include4,5:

Graphic showing common NSCLC genetic biomarkers, including EGFR mutations, BRAF mutations, ROS1 rearrangements, ALK rearrangements, and PD-L1 expression.

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for all actionable biomarkers at diagnosis of NSCLC, including EGFR, BRAF, ROS1 mutations, ALK rearrangements, and PD-L1 expression.5

Testing for EGFR mutations, which are present in a significant number of patients with NSCLC, is the focus of this website.

EGFR is an important biomarker in NSCLC and can help guide treatment decisions at the time of initial diagnosis1

EGFR can be found on the surface of both healthy cells and lung cancer cells.6

EGFR Function in Healthy Cells6

An illustration showing how EGFR activity in healthy cells leads to normal cell growth and survival.

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In some patients with metastatic NSCLC, mutations or changes in the DNA code of EGFR may help cancer cells grow.6

  • Mutated EGFR can be used as a biomarker to help identify those patients with newly diagnosed metastatic NSCLC who may be eligible to receive EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy5

ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; PD-L1, programmed death-ligand 1; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.

EGFR sensitizing mutations

Some types of EGFR mutations that help cancer cells grow and survive are considered sensitizing mutations.6,7

The most common EGFR sensitizing mutations are exon 19 deletions (in which a portion of the gene is missing) and the L858R point mutation (in which a specific part of the gene is changed).14

Exon 19 Deletions

Graphic showing an exon 19 deletion, an EGFR sensitizing mutation.

L858R Point Mutation

Graphic showing the L858R point mutation, an EGFR sensitizing mutation.

Mutant EGFR in Cancer Cells6

Illustration showing that EGFR activity in NSCLC may lead to survival, growth, and proliferation of cancer cells.

Recommendations for EGFR mutation testing at diagnosis

Identifying EGFR mutations at diagnosis has implications for making treatment decisions. Testing for biomarkers, including EGFR mutations, is recommended by a number of national clinical organizations, including:

  • National Comprehensive Cancer Network® (NCCN®)5
  • College of American Pathologists (CAP)15
  • International Association for the Study of Lung Cancer (IASLC)15
  • Association for Molecular Pathology (AMP)15
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It is important to obtain results for all actionable biomarkers, including EGFR, before making treatment decisions.

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References: 1. American Cancer Society. What is non-small cell lung cancer? http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer. Accessed August 1, 2018. 2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594. 3. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-466. doi:10.1097/COH.0b013e32833ed177. 4. Sholl LM, Aisner DL, Varella-Garcia M, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the lung cancer mutation consortium experience. J Thorac Oncol. 2015;10(5):768-777. doi:10.1097/JTO.0000000000000516. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed March 14, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 6. Baselga J. Why the epidermal growth factor receptor? the rationale for cancer therapy. Oncologist. 2002;7(suppl 4):2-8. 7. Soon YY, Vellayappan B, Tey JCS, Leong CN, Koh WY, Tham IWK. Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis. Oncotarget. 2017;8(65):109712-109722. 8. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334. doi:10.1200/JCO.2012.44.2806. 9. Rosell R, Carcereny E, Gervais R, 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):239-246. doi:10.1016/S1470-2045(11)70393-X. 10. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9(2):154-162. doi:10.1097/JTO.0000000000000033. 11. D'Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol. 2011;29(15):2066-2070. doi:10.1200/JCO.2010.32.6181. 12. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97(5):339-346. 13. Sekine I, Yamamoto N, Nishio K, Saijo N. Emerging ethnic differences in lung cancer therapy. Br J Cancer. 2008;99(11):1757-1762. doi:10.1038/sj.bjc.6604721. 14. Siegelin MD, Borczuk AC. Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab Invest. 2014;94(2):129-137. doi:10.1038/labinvest.2013.147. 15. Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018;142(3):321-346. doi:10.5858/arpa.2017-0388-CP.
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Content is consistent with the Oncology Nursing Society Standards and Guidelines. The ONS Seal of Approval does not constitute medical advice and does not imply product endorsement by ONS. Healthcare providers should exercise their own independent medical judgment. Website content or other resources referenced in these materials have not been reviewed for the ONS Seal of Approval.