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T. Sundaresan
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MS 02 - Are Non-Tissue Biomarkers Ready for the Clinic? (Presentation recordings currently in editing process) (ID 20)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:A. Hoffmann, L. Montuenga
- Coordinates: 9/07/2015, 14:15 - 15:45, 401-404
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MS02.02 - Circulating Tumor Cells (ID 1853)
14:15 - 15:45 | Author(s): T. Sundaresan
- Abstract
Abstract:
In EGFR-mutant lung cancer, acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) develops after a median of 9-14 months. The T790M gatekeeper mutation is the most common mechanism of TKI resistance, detected in >50% of tissue biopsies done after the advent of resistance. The recent clinical development of third-generation, irreversible EGFR TKIs that have preliminarily demonstrated durable tumor responses in patients who have developed the EGFR T790M mutation has generated a need for novel methods of T790M detection. Repeating tumor biopsies at the time of acquired resistance to help select second-line therapies is recommended in the NCCN guidelines. However, tissue biopsies do not always supply sufficient material for current sequencing strategies and thus may require multiple invasive procedures for adequate genotyping. Blood-based methods are more readily repeated when necessary and avoid the risks and discomfort of invasive tissue biopsies. As there may be heterogenous mechanisms of acquired resistance, a tissue biopsy of a single site of disease also may not capture the full spectrum of resistance. Blood-based methods theoretically have the potential of more comprehensively illustrating the principal mechanisms of resistance within a patient. Although there are multiple non-invasive sources of tumor-derived genetic material, circulating tumor cells (CTCs) and plasma circulating tumor DNA (ctDNA) are two that have received particular attention for blood-based genotyping. CTCs are cells shed into the bloodstream from primary and metastatic tumors that can be captured through multiple microfluidic platforms. Despite their rarity in the blood there is ongoing development of increasingly sensitive methods of CTC isolation. ctDNA is also shed into the bloodstream from tumor deposits. While more abundant than CTCs, ctDNA analysis is complicated by a high background of plasma DNA shed from normal cells. Techniques for genotyping from these blood-based sources of tumor-derived genetic material have proliferated rapidly, but there have been few studies directly comparing them. In this presentation, I will describe an exploratory study comparing T790M genotyping, using either CTCs or ctDNA versus concurrent tumor biopsies in patients with non-small cell lung cancer progressing on first line EGFR inhibitors.
