Detection of Low-Frequency Mutations in cfDNA From -Mutated NSCLC Patients After First-Line EGFR Tyrosine Kinase Inhibitors.

Background: Molecular profiling of advanced mutated NSCLC has recently demonstrated the co-existence of multiple genetic alterations. Specifically, co-existing -mutations in NSCLCs have been described, despite their prevalence at progression and their role in the response to tyrosine kinase inhibitors (TKIs) remain marginally explored. Aim of our study was to investigate the prevalence of co-existing mutations at the time of progressive disease and explore their impact on clinical outcome.

Materials And Methods: We retrospectively analyzed by digital droplet PCR prevalence of co-mutations in 106 plasma samples of mutated NSCLC patients, in progressive disease after TKI treatment as first-line therapy.

Results: co-mutations (codon 12 and 13) were identified in 3 patients (2.8% of analyzed samples), with low allelic frequency (<0.2%), and had a negative impact on clinical outcome to first-line TKI.

Conclusion: Detection of mutations in cell-free DNA of mutant NSCLC patients at progression after first or second generation TKI is a rare event. Due to their low abundance, the negative impact of mutations on the response to TKI remains to be confirmed in larger studies.