Monitoring EGFR-T790M mutation in serum/plasma for prediction of response to third-generation EGFR inhibitors in patients with lung cancer

Abstract

BackgroundOsimertinib is efficacious in lung cancer patients with epidermal growth factor receptor (EGFR) mutations and acquired resistance (AR) to EGFR tyrosine kinase inhibitors due to EGFR-T790M mutation (T790M). We sought to describe T790M changes in serum/plasma during osimertinib therapy and correlate these changes with treatment outcomes.Material and methodsSerum/plasma from EGFR-mutant lung cancer patients with T790M-AR was collected before and during osimertinib treatment. Changes in T790M were evaluated using a peptide-nucleic acid-PCR assay, and correlated with clinical and radiographic response.ResultsThirteen patients were included. Median time on osimertinib treatment was 10.6 months with a median progression-free survival of 13.6 months. Best response to osimertinib was partial response (PR), stable disease (SD) or progression (PD) in 46.1%, 30.8% and 23.1% of patients, respectively.Most of the patients were paucisymptomatic at baseline. Symptom improvement was reported in 66.6% of responder patients; while symptoms remained stable in 75% of patients with SD, and 66% of patients with PD had clinical deterioration.Three patterns of T790M changes during osimertinib treatment were identified. T790 remained detectable with PD or a short-lasting SD in 15.4% of the patients. T790M disappeared in 69.2% of patients with PR or SD. T790M disappeared, despite clinical and/or radiographic progression in 15.4% of the patients.ConclusionChanges of T790M in serum/plasma in EGFR-mutant lung cancer patients with T790M-AR might be a useful marker of symptomatic and radiographic outcome to osimertinib. Longer follow-up is needed to establish if subsequent emergence of T790M could be a marker of resistance.

Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients?

“…Importantly, LB can easily be repeated to follow the patient during treatment, allowing, e.g. the detection of minimal residual disease, relapse and mechanisms of treatment resistance [62,63].…”

Combined exosomal RNA and circulating tumor DNA for epidermal growth factor mutation detection in non-small cell lung cancer

“…The primary end point is PFS rate at 18 months. Recently, quantification of the T790M alleles fraction (AF) in patients receiving osimertinib has demonstrated to provide information about the dynamic evolution of tumor genome profiles and patients' outcomes (17). Three patterns of T790M changes were observed: in some patients T790M remained detectable, and was associated with progressive disease or a short-lasting stable disease, in other cases T790M became undetectable and patients developed partial response or stable disease, while in approximately 15% of samples T790M disappeared despite progression.…”

Molecular Targets in Lung Cancer: Study of the Evolution of Biomarkers Associated with Treatment with Tyrosine Kinase Inhibitors—Has NF1 Tumor Suppressor a Key Role in Acquired Resistance?

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