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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Evidence-based best practices for EGFR T790M testing in lung cancer in Canada
T Stockley1, C A Souza2, P K Cheema3
1Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.
Abstract:
Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as first-line systemic therapy for patients with non-small-cell lung cancer (nsclc) having mutations in the EGFR gene. Resistance to tkis eventually occurs in all nsclc patients treated with such drugs. In patients with resistance to tkis caused by the EGFR T790M mutation, the third-generation tki osimertinib is now the standard of care. For optimal patient management, accurate EGFR T790M testing is required. A multidisciplinary working group of pathologists, laboratory medicine specialists, medical oncologists, a respirologist, and a thoracic radiologist from across Canada was convened to discuss best practices for EGFR T790M mutation testing in Canada. The group made recommendations in the areas of the testing algorithm and the pre-analytic, analytic, and post-analytic aspects of clinical testing for both tissue testing and liquid biopsy circulating tumour dna testing. The recommendations aim to improve EGFR T790M testing in Canada and to thereby improve patient care.
Insights
Accurate epidermal growth factor receptor (EGFR) T790M mutation testing is crucial for non-small-cell lung cancer (NSCLC) patients resistant to TKIs. This study outlines Canadian best practices for EGFR T790M testing to enhance patient care.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are first-line therapy for EGFR-mutated non-small-cell lung cancer (NSCLC).
- Acquired resistance to TKIs, often due to the EGFR T790M mutation, necessitates alternative treatment strategies.
- Osimertinib, a third-generation TKI, is the standard of care for patients with EGFR T790M-positive NSCLC.
Framework:
- A Canadian multidisciplinary working group developed recommendations for EGFR T790M mutation testing.
- Recommendations cover testing algorithms and pre-analytic, analytic, and post-analytic considerations.
- Guidance addresses both tissue biopsy and liquid biopsy (circulating tumor DNA) testing methods.
Implementation:
- Standardized testing protocols are essential for accurate T790M mutation detection.
- Optimized pre-analytic sample handling and analytic methodologies improve test reliability.
- Clear post-analytic interpretation and reporting facilitate clinical decision-making.
Implications:
- Improved EGFR T790M testing accuracy in Canada will enhance patient management strategies.
- Standardized testing supports the effective use of targeted therapies like osimertinib.
- These recommendations aim to optimize patient outcomes in EGFR-mutated NSCLC.
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