High Concordance 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 from the plasma of advanced non–small cell lung cancer (NSCLC) patients correlates well with the EGFR mutations from patient-matched tumor tissue DNA, according to new data reported by Douillard et al in the Journal of Thoracic Oncology.
EGFR tyrosine kinase inhibitor 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 not available. A more abundant and less invasive source of tumor DNA may be cell free tumor DNA found circulating in the blood.
Study Details
International researchers prospectively analyzed and compared EGFR mutations from tumor vs matched plasma DNA and between plasma samples from 1,060 patients who were screened as part of a phase IV, open-label, single-arm study of first-line gefitinib (Iressa) in EGFR mutation–positive Caucasian patients with NSCLC.
The study found that the mutation status concordance between tumor and matched plasma for 652 patients that had results for both was 94% (95% confidence interval [CI] = 92–96) with a sensitivity of 66% (95% CI = 56–75) and specificity of 100% (95% CI = 99–100). The reproducibility between two plasma specimens from the same patient was also high with a mutation concordance of 97% (95% 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 [95% CI = 8.5–11.0]) vs both EGFR mutation–positive tissue and plasma (10.2 months [95% CI = 8.5–12.5]).
Study Implications
“Tumor tissue should be considered the preferred sample type when available,” the authors acknowledged. “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.… As there are no published guidelines for the use of ctDNA for EGFR mutation analysis in the absence of tumor tissue, these results may help address this current unmet need.”
Lead author Jean-Yves Douillard, MD, PhD, of the Integrated Centres of Oncology R. Gauducheau and University of Nantes Medical School, France, said that the next steps are to look for resistance mutations (such as T790M) during treatment so as to better understand the mechanisms of resistance. For future research he also suggested “searching for other resistance mutations along the EGFR pathway, as well as other related pathways, and improving the sensitivity by using more powerful testing methods, like next generation sequencers.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
