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D. Berz
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-012 - Longitudinal Monitoring of ctDNA EGFR Mutation Burden from Urine Correlates with Patient Response to EGFR TKIs: A Case Series (ID 5717)
14:30 - 14:30 | Author(s): D. Berz
- Abstract
Background:
Circulating tumor DNA (ctDNA) are short DNA fragments released into the systemic circulation by rapid cell turnover, and excreted into the urine. Urinary ctDNA-based detection of oncogenic mutations is a non-invasive modality that can help in clinical decision-making, especially when tissue biopsies are not available. When conventional imaging modalities are inconclusive, quantitative assessment of systemic ctDNA burden has the potential to assess response to therapy. In this case series we assessed EGFR mutation status at baseline and at intervals following administration of tyrosine kinase inhibitor (TKI) therapy to determine whether EGFR systemic mutation load correlated with disease burden and therapeutic response.
Methods:
Four patients on anti-EGFR (TKI) were prospectively monitored for quantitative assessment of systemic mutant allele burden of activating and resistance EGFR mutations (Exon 19 deletions, L858R and T790M) in urine. EGFR mutations were quantitatively interrogated by short footprint mutation enrichment PCR followed by next-generation sequencing assays. Systemic mutant allele burden was compared to assessment of tumor burden computed by standard imaging modalities.
Results:
Patients 1, 2, and 3 were originally diagnosed with EGFR-positive NSCLC. Targeted molecular testing of systemic urine ctDNA revealed high EGFR mutation burden and the presence of the T790M resistance mutation at the time of progression on TKI therapy (>550 copies/10[5] genome equivalents (GEq)). Interestingly, the extent of radiographic progression in patient 3 was not completely clear, and urinary T790M along with clinical assessment of pain helped determine progression prior to obtaining pleural effusion results. After initiation of a 3[rd] generation TKI (patient 1: ASP8273, patients 2 and 3: osimertinib), all patients experienced an appreciable decrease in the EGFR mutation burden, which was consistent with clinical improvement prior to radiographic imaging. Patient 4 presented with multiple lung nodules at diagnosis and a high systemic L858R mutant allele burden (>550 copies/100,000 GEq). Two months after initiation of first-line TKI, the main lesion and lymph nodes slightly improved, but the lung nodules progressed. The high systemic L858R burden persisted at the same level as pre-therapy.
Conclusion:
Urinary ctDNA-based quantitative assessment of systemic EGFR mutant allele burden is a non-invasive molecular diagnostic testing modality that correlates with tumor burden and response to therapy.
