EGFR mutation testing in lung cancer prior to tyrosine kinase inhibitor (TKI) therapy can be performed in tissue or plasma in practice. Both techniques are complementary; however, plasma testing can represent a surrogate for re-sampling a tumour in patients progressing under TKI prior to prescription of osimertinib, but clinical sensitivity of the test remains to be determined. We present our twelve-month experience of integrating EGFR plasma testing into our service with a series of 262 cases. We currently receive over 50 cases per month.
EGFR mutation testing for both tissue and plasma is performed using cobas EGFR Mutation Test v2, which covers 29 deletions in exon 19, T790M, L858R, G719X, S768I, L861Q and 5 insertions in exon 20. For plasma testing, DNA is extracted using the cobas cfDNA sample preparation kit. All samples were submitted in Paxgene ccfDNA tubes.
Of the 262 cases submitted for testing, five failed (1.9%). 123 mutations, including 42 T790M, were detected. Turnaround time was two days. Clinical sensitivity is very difficult to assess because of the uncertainty of the presence of circulating tumour DNA at all. All types of primary mutation were detected: 70 exon 19 deletions, 42 L858R, 2 G719X, 5 L861Q, 3 combined S768I and G719X, and 1 singlet T790M. Clinical details were not available for all patients. A sensitising mutation was found in 51 of 92 patients (55.5%) under TKI therapy, where this was indicated on the request form; among these, an associated T790M mutation was found in 19 (37%) of patients. Several patients underwent multiple tests while they received TKI therapy; in two patients, the secondary mutation was detected prior to clinical progression.
We show here that EGFR plasma testing is perfectly suitable for clinical practice; it is highly specific and cost-effective due to rapid turnaround times, but the low sensitivity renders it complementary to tissue testing rather than a true surrogate.
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All authors have declared no conflicts of interest.