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S.W. Yeung

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-028 - Droplet digital PCR: A novel detection method of activating Epidermal Growth Factor Receptor (EGFR) mutations in plasma of patients with advanced stage non-small cell lung cancer (NSCLC) (ID 2811)

      09:30 - 16:30  |  Author(s): S.W. Yeung

      • Abstract

      In-frame deletion at exon 19 and point mutation at exon 21 are the two most common activating mutations in EGFR tyrosine kinase accounting for >85% of all clinical relevant EGFR mutations. In this study, we aim to develop a highly sensitive method to detect and quantify these two mutations in plasma of patients with advanced non-small cell lung cancer (NSCLC) using droplet digital PCR (ddPCR).

      We analyzed 208 plasma samples from patients with advanced NSCLC from the ASPIRATION study using the QX100 ddPCR system (BioRad). ASPIRATION study is a single arm study on the use of first line erlotinib in patients with EGFR mutation (confirmed from tissue samples) and test the concept of treatment beyond RECIST progression. 36 archived plasma samples with known EGFR wild type were used as control. ddPCR simultaneously performs PCR reactions in 20,000 DNA containing droplets, and for each plasma sample we measured the absolute quantities of circulating EGFR mutant and wild-type sequences partitioning in discrete droplets.

      Specific ddPCR assays were developed for detecting EGFR exon 19 deletion and L858R mutation independently. 126 (61%) of 208 plasma samples were positive for EGFR mutation (63 cases for Exon 19 deletion, 63 cases for L858R). Table 1 summarizes the concordance of the tissue and plasma analysis. Sensitivity is 61%, specificity is 94% and positive predictive value is 98%. The mean absolute concentration for detectable exon 19 deletion and L858R in plasma is 1,060 and 1,510 copies/ml plasma respectively. Mean fractional concentration is 11%. Further correlation between plasma EGFR mutation results and clinical data will be performed.

      Table 1
      EGFR mutation Tumor tissue +ive Tumor tissue -ive
      Plasma ddPCR +ive 126 2 128
      Plasma ddPCR -ive 82 34 116
      208 36 244

      Droplet digital PCR analysis is a novel sensitive detection method for EGFR mutation in plasma of patients with advanced NSCLC. Quantification of low level of circulating EGFR mutant DNA is feasible. Future investigation aims to correlate the quantified plasma EGFR mutation DNA with clinical outcomes.