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MINI 26 - Circulating Tumor Markers (ID 148)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
MINI26.14 - Noninvasive Identification of EGFR-T790M Mediated Resistant NSCLC Patients Using Plasma CfDNA (ID 1208)
16:45 - 18:15 | Author(s): J. Zhang
EGFR-T790M mutation, which is the valuable target for the next generation of EGFR-TKI, accounts for about half of the acquired resistance to current EGFR-TKI therapy in the EGFR sensitive mutation positive NSCLC patients. Due to clinical challenge in obtaining re-biopsy tumor tissues, noninvasive detection of EGFR-T790M in plasma circulating free DNA (cfDNA) has been proved to be feasible. Yet a highly sensitive assay needs to be developed to avoid false-negative detection. We here explored whether droplet digital PCR (ddPCR) of cfDNA can an alternative assay to identify the EGFR-TKI resistance mediated by EGFR-T790M in the clinical practice.
The digital PCR method was recently developed for EGFR sensitive mutations, and its high sensitivity and specificity were validated in plasma cfDNA from EGFR-TKI-naïve NSCLC patients. In this study, we applied this method to detect EGFR-T790M in plasma cfDNA from metastatic NSCLC patients who initially responded but acquired resistance to current EGFR-TKI treatment. For the concordance analysis, the paired re-biopsy or pleural effusion cytology samples after failed EGFR-TKI were also collected for EGFR-T790M testing.
25 consecutive NSCLC patients were enrolled and analyzed in this study according to these criteria: 1. Metastatic NSCLC patients with acquired EGFR-TKI resistance. 2. The re-biopsy tissue or cytology samples and paired plasma samples were available after disease progression on EGFR-TKI. Among these 25 patients, 13 were positive and 9 were negative for EGFR-T790M mutation in both tumor tissue and plasma samples. 3 patients positive for EGFR-T790M mutation in tumor tissue were detected negative in their plasma. The overall concordance rate between plasma and tumor tissue testing was 88.00% (22/25) (Kappa=0.757, 95%CI: 0.4996-1.0). The sensitivity and specificity for plasma testing of EGFR-T790M mutation by ddPCR were 81.25% (13/16) (95%CI: 54.35%-96.00%) and 100.00% (9/9) (95%CI: 66.37%-100%), respectively. Figure 1
Detection of EGFR-T790M in plasma cfDNA by ddPCR is highly sensitive and specific when compared to the pairedre-biopsy tissue or cytology samples. This noninvasive method could complement current invasive biopsy approach or provide an alternative method to identify specific mutation mediated resistance in clinic.
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