Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories

Leighl, N., Kamel-Reid, S., Cheema, P. K., Laskin, J., Karsan, A., Zhang, T., Stockley, T., Barnes, T. A., Tudor, R. A., Liu, G., Owen, S., Rothenstein, J., Burkes, R. L., Iqbal, M., Spatz, A., van Kempen, L., Izevbaye, I., Laurence, D., Le, L. W. & Tsao, M-S., Jun-2020, In : JCO Precision Oncology. 3, p. 520-533 14 p.

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  • Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories

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  • Natasha Leighl
  • Suzanne Kamel-Reid
  • Parneet K. Cheema
  • Janessa Laskin
  • Aly Karsan
  • Tong Zhang
  • Tracey Stockley
  • Tristan A. Barnes
  • Roxana A. Tudor
  • Geoffrey Liu
  • Scott Owen
  • Jeffrey Rothenstein
  • Ronald L. Burkes
  • Mussawar Iqbal
  • Alan Spatz
  • L. van Kempen
  • Iyare Izevbaye
  • David Laurence
  • Lisa W. Le
  • Ming-Sound Tsao
PURPOSE Plasma detection of EGFR T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories.
PATIENTS AND METHODS Sixty-three patients with advanced EGFR-mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial ( identifier: NCT02474355), participated in this companion study. Plasma T790M mutation was detected using droplet digital polymerase chain reaction, Cobas (Roche Diagnostics, Indianapolis, IN), or next-generation sequencing in 4 laboratories. T790M concordance was assessed between plasma and tumor samples.
RESULTS Assessment of T790M in tumor biopsy tissue was successful in 81% of patients; 49% had confirmed
T790M results (tumor or plasma) for ASTRIS. Plasma testing in this companion study yielded T790M results in
97% of patients; 62% had T790M-positive results, 36% had negative results, and 2% had indeterminate results.
Of 38 patients with negative or indeterminate biopsy results, 55% had positive plasma T790M results, increasing the proportion with T790M-positive results to 73%. Sensitivity of plasma T790M testing was 75%. Overall concordance between tissue and plasma was 64%, and concordance among laboratories was 90.3%. Response to osimertinib and duration of therapy were similar irrespective of testing method (overall response rate, 62.5% for tissue, 66.7% for plasma, and 70.6% for both).
CONCLUSION This multicenter validation study demonstrates that plasma EGFR T790M testing can identify significantly more patients than biopsy alone who may benefit from targeted therapy.
Original languageEnglish
Pages (from-to)520-533
Number of pages14
JournalJCO Precision Oncology
Publication statusPublished - Jun-2020
Externally publishedYes

ID: 125277301