High concordance seen between EGFR mutations from circulating free tumor DNA and tumor tissue in NSCLC

Epidermal growth factor receptor (EGFR) mutations found in the circulating free tumor DNA (ctDNA) from the plasma of advanced non-small cell lung cancer (NSCLC) patients correlates well with the EGFR mutations from patient-matched tumor tissue DNA.

Why is this significant? EGFR tyrosine kinase inhibitor (TKI) therapy is approved for EGFR activating mutation-positive patients with advanced NSCLC, but the standard for determining mutation status is with DNA derived directly from tumor tissue, which can be limited or unavailable. Cell-free tumor DNA found circulating in the blood may be a more abundant and less invasive source of tumor DNA.

Researchers prospectively analyzed and compared tumor and matched plasma DNA for EGFR mutations from 1,060 patients who were screened as part of a phase IV, open-label, single-arm, first-line gefitinib trial in EGFR mutation-positive Caucasian patients. Also, when two plasma samples from the same patient were available, the mutation status of each was compared.

Published in the Journal of Thoracic Oncology, the study reports that the mutation status concordance between tumor and matched plasma for 652 patients who had results for both was 94% (95% CI 92-96) with a sensitivity of 66% (CI 56-75) and specificity of 100% (CI 99-100). The reproducibility between two plasma specimens from the same patient was also high, with a mutation concordance of 97% (CI 94-99) for 224 matched specimens. Post-hoc analysis of the efficacy of first-line gefitinib revealed there was similar progression-free survival for those with EGFR mutation-positive tissue (9.7 months [CI 8.5-11.0]) versus both mutation-positive tissue and plasma (10.2 months [CI 8.5-12.5]).

“Tumor tissue should be considered the preferred sample type when available,” the authors say. “However, our encouraging results suggest that a single plasma-derived ctDNA sample may be considered appropriate for assessment of EGFR mutation status when tumor tissue is unavailable or exhausted.” Read the study abstract.