Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.
Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.
The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.
Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).
Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.
Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.
“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”
“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.
Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.
SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. .