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Sebastian Oltean
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-66 - Detection of Genomic Mutations in Blood and Urine ctDNA in Lung Adenocarcinoma with EGFR Mutation on Tissue – An Interim Progress Report (Now Available) (ID 2766)
08:00 - 18:00 | Author(s): Sebastian Oltean
- Abstract
Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective therapy for stage IIIB/IV EGFR-mutation positive (EGFRm+) NSCLC. Despite initial response, clinical progression occurs, often with development of a second TK mutation.
Mutation analysis is performed at time of diagnosis usually on single tissue biopsy. Samples can be difficult to obtain and may not represent neoplastic tissue at other sites due to heterogeneity. On progression, patients rarely undergo repeat tissue biopsy. Therapy is no longer truly personalised.
CtDNA may be an alternative to tissue biopsy for mutation analysis. It may be more representative, and provide real time assessment of disease status, maintaining individualised therapy.
Published retrospective data are available on detection of EGFR mutations in plasma ctDNA, and evidence that urine can be used is emerging. Clinical use has been limited by lack of evidence for detection methods and concordance with tissue.
Retrospective data suggest that on response to TKI, TK mutation load reduces, and on progression, mutation load increases and/or a new mutation emerges. This has not been validated prospectively.
Method
A prospective pilot study: 20 patients, 2 UK sites; with stage IIIB/IV EGFRm+ NSCLC on tissue sample, TKI-treatment naïve. Plasma and urine collected prior to TKI treatment and monthly on treatment. CtDNA is extracted from plasma and urine using Quigen kit, and analysed using digital droplet PCR for the 3 most common EGFR mutations – del19, L858R and T790M.
Objective: To investigate if urine/plasma ctDNA may be used to prospectively detect and monitor EGFR mutational status at baseline and during TKI therapy
Primary Endpoint: To assess if ctDNA from urine/plasma could be a reliable source of EGFR testing
Secondary Endpoint: To assess if changes in levels of baseline mutation or development of new mutations in ctDNA correlates with disease response/progression during TKI therapy
Outcome: To inform development of a larger study to further investigate and validate the role of liquid biopsy in treatment of EGFRm+ NSCLC
Result
CtDNA analysis performed on samples from 14patients to date. On baseline tissue, 8 (57%) had del19 mutation, 5 (36%) had L858R mutation, and 1 (7%) had L861Q mutation. Representative of population distribution of EGFR mutations.
In those with tissue del19 mutation, del19 mutation was identified on baseline ctDNA in 8/8 (100%) plasma samples and 6/7 (86%) urine samples (one patient did not provide baseline urine sample). None had L858R mutation in plasma/urine. In one plasma ctDNA sample, very low levels of T790M mutation were identified, but no T790M mutations were found in urine ctDNA.
In those with tissue L858R mutation, L858R mutation was identified on baseline ctDNA in 3/5 (60%) plasma samples and 4/5 (80%) urine samples. All were found to have del19 mutation on baseline plasma ctDNA, 3/5 had del19 mutation in urine ctDNA. None had T790M mutations in plasma/urine ctDNA.
Conclusion
Sensitivity is high for identifying baseline EGFR mutations in plasma/urine ctDNA.
Very hard to comment on specificity. It's known that del19 and L858R mutations can co-exist. It's possible that mutation analysis performed on DNA extracted away from primary tumour site may carry additional mutations due to heterogeneity.
