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Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical
Natasha B Leighl1, Suzanne Kamel-Reid1, Parneet K Cheema2
1University Health Network, Toronto, Ontario, Canada.
JCO Precision Oncology
|January 20, 2022
Summary
Plasma testing for EGFR T790M mutations offers a more effective way to identify lung cancer patients who can benefit from targeted therapy compared to biopsy alone. This method improves detection rates and supports treatment decisions.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant challenge in advanced non-small cell lung cancer (NSCLC).
- The T790M mutation in EGFR is a key mechanism of acquired resistance to first and second-generation EGFR TKIs.
- Plasma-based detection of EGFR mutations is emerging as a less invasive alternative to tumor rebiopsy for identifying T790M mutations.
Purpose of the Study:
- To validate the analytical sensitivity and clinical utility of plasma EGFR T790M mutation detection.
- To compare the diagnostic yield of plasma testing versus tumor biopsy for T790M mutations in patients with advanced EGFR-mutant lung cancer.
- To assess the concordance of plasma T790M results with tumor biopsy results and among different laboratories.
Main Methods:
- A multicenter study involving 63 patients with advanced EGFR-mutant lung cancer screened for the ASTRIS trial.
- Plasma T790M mutation detection was performed using droplet digital PCR, Cobas, or next-generation sequencing across 4 laboratories.
- Concordance analysis was conducted between plasma and tumor samples, and inter-laboratory agreement was assessed.
Main Results:
- Plasma testing yielded T790M results in 97% of patients, with 62% testing positive, significantly increasing the detection rate compared to tumor biopsy (49% success rate).
- In patients with negative or indeterminate tumor biopsy results, plasma testing identified T790M mutations in 55%, raising the overall T790M-positive rate to 73%.
- Plasma T790M testing demonstrated a sensitivity of 75% and an overall concordance of 64% with tissue testing, while inter-laboratory concordance was high at 90.3%.
Conclusions:
- Plasma EGFR T790M testing is a valuable tool that significantly increases the identification of patients eligible for targeted therapy compared to biopsy alone.
- The findings support the clinical utility of plasma T790M testing for guiding treatment decisions in EGFR-mutant lung cancer.
- Further validation is warranted for routine implementation in clinical diagnostic laboratories.
