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B. Klughammer

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    O01 - Prognostic and Predictive Biomarkers I (ID 94)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O01.06 - Dynamic change in plasma EGFR mutation DNA in response to first line therapy for advanced stage non-small cell lung cancer (NSCLC) (ID 2496)

      10:30 - 12:00  |  Author(s): B. Klughammer

      • Abstract
      • Presentation
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      Diagnostic utility study of EGFR mutation analysis of tumor and plasma from FASTACT 2 confirmed that the plasma EGFR mutation DNA (pEGFRmut) is a sensitive and specific biomarker. (Wu et al, Lancet Oncology 2013; T. Mok, ASCO 2013). Primary objective of this study is to investigate the dynamic change in pEGFRmut during course of treatment. Secondary objective is to study the diagnostic utility of pEGFRmut in patients with distant organ metastasis whom we assumed to have higher level of plasma DNA.

      Retrospective EGFR mutation testing of FFPET and plasma from FASTACT 2 were performed with two allele-specific assays, cobas® 4800 EGFR_FFPET test and cobas® EGFR_blood test (in Development). Both tests are designed to detect one or more of the 42 known EGFR mut. One FFPET section was used for tissue test and 2-ml plasma was used for blood test. We studied the plasma samples collected at baseline, post cycle 3 (C3) and at tumor progression according to RECIST criteria (PD).

      Complete analysis of plasma samples at baseline, C3 and PD was available in 305 of 451 pts(67.6%). Incidence of pEGFRmut positive at baseline, C3 and PD was 35% (106/305),15% (47/305)and 27% (81/305), respectively. 98 of 106 pEGFRmut patients harbor the Exon 19 deletion or L858R at baseline. (C arm 51; CE arm 47). At C3, 21 (41%) pts lose pEGFRmut positivity in C arm comparing to 39 (83%) in CE arm. At PD, 8 of the 21pts in C arm and 18 of the 39 in CE arm regained pEGFRmut positivity. Table 1 summarized the median pEGFRmut copies/PCR. There was a considerable decline at C3 in both C and CE arm. However, pEGFRmut copies/PCR rebounded to high level at PD in C arm only and remained low in CE arm. Correlation of dynamic change in pEGFRmut copies/PCR with clinical tumor response and PFS will be presented at the meeting. We have also identified 93 (out of 224 matched tissue and plasma samples) patients with known distant organ metastasis. Sensitivity of pEGFRmut in this patient subgroup is 91% (41/45), specificity at 98% (47/48) and overall concordance at 95% (88/93). Table 1

      Median pEGFRmut copies/PCR Baseline C3 PD
      C (Exon 19) 27.6 2.3 35.8
      CE (Exon 19) 43.2 0 2.7
      C(Exon 21) 40.9 2.6 63.9
      CE (Exon 21) 87.1 0 3.5

      This is the first study demonstrating the quantitative dynamic change in pEGFRmut in pts who received C or CE for advanced NSCLC. At RECIST progression, pEGFRmut remained low in patients who received erlotinib but not in patients who received chemotherapy only. pEGFRmut is a potential biomarker for monitoring tumor response.

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