Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) resistance mutation in Pre-treatment Non-small cell lung carcinomas harboring activating EGFR mutations and correlation with clinical outcomes

L. Ye; N. Mesbah Ardakani; C. Thomas; K. Spilsbury; C. Leslie; B. Amanuel; M. Millward

doi:10.1007/s12253-020-00833-z

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Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) resistance mutation in Pre-treatment Non-small cell lung carcinomas harboring activating EGFR mutations and correlation with clinical outcomes

Journal article

Peer reviewed

Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) resistance mutation in Pre-treatment Non-small cell lung carcinomas harboring activating EGFR mutations and correlation with clinical outcomes

L. Ye, N. Mesbah Ardakani, C. Thomas, K. Spilsbury, C. Leslie, B. Amanuel and M. Millward

Pathology & Oncology Research

2020

DOI: https://doi.org/10.1007/s12253-020-00833-z

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Abstract

Increasing evidence points to the presence of low-level de novo T790M mutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations. T790M was detected in 42 of 109 pre-treatment samples (38.5%). Median variant allele frequency was 0.14% (range 0.02–28.5%). Overall response rate to first generation EGFR tyrosine kinase inhibitors (TKI) was 67% regardless of T790M status. The median progression free survival was 10.7 (IQR 5.6–19.9) versus 6.7 (IQR 3.5–20.8) months in T790M negative and positive patients respectively. T790M positivity correlated with increased rate of early disease progression. It also correlated with increased mortality (HR 3.1 95%CI 1.2–8.1, p = 0.022) in patients who did not respond to TKI treatment. We detected a significant rate of low-level pre-treatment T790M mutations in NSCLC using highly sensitive dPCR. Low-level pre-treatment T790M did not impact treatment response rate or overall survival, but was associated with increased rate of early progression on TKI therapy.

Details

Title: Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) resistance mutation in Pre-treatment Non-small cell lung carcinomas harboring activating EGFR mutations and correlation with clinical outcomes
Authors/Creators: L. Ye (Author/Creator) - The University of Western Australia
N. Mesbah Ardakani (Author/Creator)
C. Thomas (Author/Creator) - The University of Western Australia
K. Spilsbury (Author/Creator) - The University of Notre Dame Australia
C. Leslie (Author/Creator) - The University of Western Australia
B. Amanuel (Author/Creator) - Edith Cowan University
M. Millward (Author/Creator) - Sir Charles Gairdner Hospital
Publication Details: Pathology & Oncology Research
Publisher: Springer
Identifiers: 991005540444807891
Copyright: © 2020 Springer Nature Switzerland AG.
Murdoch Affiliation: School of Veterinary and Life Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.199 Lung Cancer; 1.199.581 NSCLC Treatments
Web Of Science research areas: Oncology; Pathology
ESI research areas: Clinical Medicine