The emergence of novel targeted treatments for clinically actionable mutations, such as Tyrosine Kinase Inhibitors (TKI) for somatic EGFR mutations in non-small cell lung cancer (NSCLC) patients, has revolutionised treatment for these patients and improved progression free survival (PFS) and overall survival (OS) in patients with tumours where these mutations are present [1]. Unfortunately, all patients on this treatment will ultimately progress, and in over half of cases this is due to acquisition of the secondary somatic EGFR-T790M mutation by the tumour, whereby an amino acid substitution resurrects the ability of the tumour to proliferate. With recent evidence of efficacy and regulatory approval of Osimertinib (a third-generation irreversibly binding EGFR-TKI), for the treatment of metastatic NSCLC that harbours the EGFR-T790M mutation, this mutation has emerged as a biomarker for treatment in patients with NSCLC with acquired resistance to prior EGFR-TKI therapy. Up until recently, a tumour tissue sample was necessary for the detection of T790M, however it is not always possible to obtain adequate material from one procedure and some patients may refuse, or be unfit for further tumour sampling. Invasive biopsies are also associated with considerable resource utilisation and potential for iatrogenic injury.
The non-invasive detection of EGFR mutations and particularly T790M in plasma and other body fluids is an area of considerable research interest. Efforts to detect EGFR mutations in cell free DNA (cfDNA) have led to an FDA-approved plasma based assay (Roche), however the detection of T790M has proved problematic with limited sensitivity. Given that Osimertinib is effective in NSCLC patients with T790M-mediated TKI resistance, any bodily fluid which improves T790M mutation detection is potentially very exciting and clinically impactful.
Exhaled breath condensate (EBC) is a form of liquid biopsy, derived from airway lining fluid, which has been shown to harbour cfDNA and mutations associated with lung cancer. Our group, in preliminary studies, has detected tumour specific mutations, including T790M, in the EBC of lung cancer patients. The primary objective of this current study is to compare the sensitivity of EBC with reference standard plasma-based testing in detecting the EGFR-T790M mutation in patients with EGFR-T790M positive NSCLC.
