About EGFR-Mutated Lung Cancer

About EGFR-Mutated Lung Cancer

Learn more about EGFR mutation, the most common type of gene mutation in lung cancer

EGFR Mutation Testing

EGFR mutation testing is used primarily to help guide treatment and determine whether someone with non-small cell lung cancer (NSCLC) may benefit from targeted therapy such as the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy.

 

What is an EGFR mutation test? 

EGFR mutations can lead to uncontrolled growth of cancer cells.24 An EGFR mutation test is to look for the presence or absence of EGFR mutations in the tumour. It can help determine which treatment options might be best for patients with NSCLC.

 

Testing for EGFR mutation may be recommended if a patient has the adenocarcinoma sub-type of NSCLC, though other sub-types can also have EGFR mutation.25

 

How to get tested

If there is enough tissue from the original biopsy of a patient’s tumour, this tissue can be tested. If not, a second biopsy to get enough tissue to test may be needed. Some doctors may also want a second biopsy to see if a patient has developed a new mutation called T790M mutation at the failure of first line EGFR-targeted therapy.25 The T790M mutation will cause resistance to EGFR-targeted drugs.25 See About EGFR T790M Mutation section for more information.

 

In general, results of an EGFR mutation test are available in 1 to 3 weeks’ time.25

 

Apart from using tumour tissue for testing, other new approaches are being used, including “liquid biopsy,” such as circulating tumour DNA (ctDNA) test which uses blood to study gene changes.26 These tests help guide treatment decisions when additional biopsies are not possible.

 

It is recommended that all patients with advanced NSCLC and adenocarcinoma histology be tested for EGFR mutations.48

 

Testing at diagnosis

At primary diagnosis of advanced NSCLC, EGFR mutation test results help physicians to decide if a patient is likely to benefit from treatment with an EGFR-TKI. When testing for EGFR mutations, it is recommended that a tumour sample be used to confirm the presence of EGFR mutations prior to treatment. However, circulating ctDNA obtained from blood (plasma) may be used if a tumour sample is not available.49

 

The diagram below outlines the process of testing at diagnosis using tissue and plasma samples.49

Testing at progression

At disease progression, the most common mechanism of acquired resistance to first line EGFR-TKIs is the EGFR T790M mutation.50-53 Studies have shown that the incidence of the EGFR T790M mutation in tumours that have developed resistance to first line EGFR-TKIs ranges from 51% to 68%.50-54

 

Therefore, it is highly recommended to test EGFR T790M mutation at the time of disease progression.55-57 Testing for the T790M mutation is now possible using similar methods to those for EGFR mutation testing at the time of primary diagnosis. EGFR T790M mutation status can be verified using either a tissue-based or plasma-based test.57

 

The diagram below outlines the process of testing at progression using plasma and tumour samples.57

 

 

Following disease progression, it can be more challenging to obtain a tissue biopsy than at primary diagnosis. ctDNA obtained from a plasma sample offers a less invasive and potentially quicker alternative for EGFR mutation testing. However, ctDNA testing is less sensitive for EGFR T790M,58 with a false negative result of about 30% to 40%.59,60 Therefore, if a plasma-based ctDNA test is used and the result is negative, it is recommended that this be followed-up with a tissue-based test.57 However, if a tumour sample is not available, a second plasma test can be considered.61

 

 

 

 

 

 

24. AACC. EGFR Mutation Testing. Available at:https://labtestsonline.org/tests/egfr-mutation-testing. Accessed: 3 May 2019.

25. freetobreathe. New Lung Cancer Treatment Possibilities Through Molecular Tumor Testing. Available at: http://www.freetobreathe.org/images/uploads/MTTBrochure-2017update.pdf. Accessed: 9 Feb 2017.

26. Ma MW, et al. Ann Transl Med 2015;3(16):235.

48. IASLC. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors. Available at: https://www.jto.org/article/S1556-0864(17)33071-X/pdf. Accessed: 4 May 2019.

49. RESSA EMA. Summary of Product Characteristics. Available at: https://www.egfr-mutation.com/order-patterns.html. Accessed: 4 May 2019.

50. Oxnard GR, et al. Clin Cancer Res 2011; 17: 1616-1622.

51. Sun JM, et al. Lung Cancer 2013; 82: 294-298.

52. Kuiper JL, et al. Lung Cancer 2014; 85: 19-24.

53. Li W, et al. Lung Cancer 2014; 84: 295-300.

54. Arcila ME, et al. Clin Cancer Res 2011; 17: 1169-1180.

55. Yang SH, et al. Clin Cancer Res 2005; 11: 2106-2110.

56. Tagrisso Prescribing Information. Sep 2016.

57. Tagrisso Summary of Product Characteristics. Sep 2016.

58. cobas® EGFR Mutation Test v2 [package insert]. 2016.

59. Thress KS, et al. Lung Cancer 2015; 90: 509-515.

60. Oxnard GR, et al. J Clin Oncol 2016; 34: 3375-3382.

61. Stockley T, et al. Curr Oncol. 2018;25(2):163-169.