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Australian recommendations for EGFR T790M testing in advanced non-small cell lung cancer
Thomas John1, Jeffrey J Bowden2, Stephen Clarke3
1Austin Health, Heidelberg, Victoria, Australia.
Abstract:
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as first-line therapy in patients with non-small cell lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene. Unfortunately, resistance to these therapies often occurs within 10 months of commencing treatment and is mostly commonly due to the development of the EGFR T790M mutation. Treatment with the third-generation EGFR TKI, osimertinib can prolong progression free survival in patients with the T790M mutation, so it is important to determine the resistance mechanism in order to plan ongoing therapeutic strategies. Here we review the evidence and make recommendations for the timing of T790M mutation testing, the most appropriate specimens to test and the available testing methods in patients progressing during treatment with first line EGFR TKIs for NSCLC.
Insights
Testing for the T790M mutation is crucial for patients with non-small cell lung cancer (NSCLC) who develop resistance to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This review guides optimal T790M testing strategies to inform subsequent treatment decisions.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- First-generation EGFR TKIs are first-line treatments for EGFR-mutated NSCLC.
- Resistance to these TKIs, often due to the T790M mutation, typically emerges within 10 months.
- Osimertinib, a third-generation TKI, is effective against the T790M mutation.
Purpose of the Study:
- To review evidence on T790M mutation testing in NSCLC patients.
- To provide recommendations on the optimal timing and specimen types for T790M testing.
- To discuss available methods for detecting the T790M resistance mutation.
Main Methods:
- Literature review of studies on T790M mutation testing.
- Analysis of diagnostic methods for EGFR T790M detection.
- Evidence-based recommendations for clinical practice.
Main Results:
- T790M mutation is the most common resistance mechanism to first-generation EGFR TKIs.
- Timely T790M testing is essential for guiding treatment selection.
- Various specimen types (tissue, liquid biopsy) and testing methods are available.
Conclusions:
- Accurate and timely T790M mutation testing is critical for managing acquired resistance in EGFR-mutated NSCLC.
- Recommendations are provided for optimizing T790M testing strategies.
- Informing treatment decisions with T790M status improves patient outcomes.
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