EGFR T790M (Plasma)

NOTE: Our laboratory offers multiple testing options for non-small cell lung cancer. Please see our Lung Cancer overview page.

OVERVIEW

Non-small cell lung cancers with activating EGFR mutations commonly develop acquired resistance to first- and second-generation anti-EGFR TKI therapies.  In approximately 50-60% of cases, development of the secondary T790M mutation in EGFR is responsible for TKI therapy resistance. However, the T790M mutation has been shown to remain sensitive to treatment with osimertinib. 

INDICATION

  • Non-small cell lung adenocarcinoma progressing on first-line EGFR TKI therapy

TEST REQUIREMENTS

  1. Completed CGL Solid Tumour Testing requisition form <page link>
    1. Select: Progression: Plasma cfDNA
    2. In Reason for Testing/Clinical History, indicate the EGFR activating mutation detected at diagnosis if this testing was not performed at CGL. Providing the activating change reduces the likelihood of an Uninformative result.
  2. Plasma circulating DNA (ctDNA) (see Sample Guidelines)
    1. Peripheral blood collected in Streck cfDNA tubes (2 x 10mL)

TURN-AROUND TIME

Fourteen calendar days from receipt of specimen and completed, signed requisition form.

METHOD

Peripheral blood is collected in Streck cfDNA tubes and the circulated tumour DNA in the plasma is isolated following manufacturer’s recommendations.  Quantitative amplification is performed with primers and probes specific to EGFR T790M, L858R, G719X, and most exon 19 deletions, followed by analysis using the Biorad QX200 Droplet Digital PCR System.  The lower limit of detection for the EGFR T790M mutation in plasma is approximately 0.06% variant allele frequency.

RESULTS REPORTING

  • Results are reported as positive or negative for the presence of the EGFR T790M mutation and for the initial activating mutation in the tumour (if known and detectable by this assay)
  • The result may be reported as Uninformative if the assay was unable to detect the presence of either T790M or the initial activating mutation in the tumour.  In this circumstance, the amount of tumour DNA (if any) in the plasma is uncertain, and the negative result cannot be confidently interpreted.  Repeat testing can be considered (see below).

REPEAT TESTING

The amount of circulating tumour DNA may change over time.  Following an uninformative result, a non-immediate repeat analysis from a new peripheral blood draw can be considered.  Circulating tumour DNA may increase in concentration following a period of time, such as six weeks, or following therapies that result in significant tumour lysis.

Alternatively, an analysis of tumour tissue collected post-progression could be considered.

REFERENCES

  1. Melosky et al. Current Oncology (2018) PMID:29507487
  2. Mok et al. New England Journal of Medicine (2017) PMID:27959700