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Y. Wang



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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.09 - Dynamic, quantitative, and non-invasive analysis ofT790M mutation in matched plasma DNA from pre-and post-EGFR-TKI treatment for advanced non-small cell lung cancer (ID 2568)

      11:20 - 11:25  |  Author(s): Y. Wang

      • Abstract
      • Presentation
      • Slides

      Background
      Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer patients (NSCLC) is attributed to the T790M mutation of EGFR. Here, we evaluated T790M mutation using dynamic, quantitative and non-invasive method and explored its role predicting outcomes of EGFR-TKI treatment.

      Methods
      We enrolled 135 EGFR-TKI-resistant NSCLC patients in the study. Pre- and post-EGFR-TKI treatment (pre-TKI and post-TKI, respectively) plasma samples were obtained for analysis. T790M mutation was measured qualitatively and quantitatively by the amplification refractory mutation system (ARMS) and digital polymerase chain reaction (D-PCR).

      Results
      D-PCR was more sensitive than ARMS in detecting the T790M mutation (pre-TKI: 29.4% (32/109) vs 5.5% (6/109), P<0.001; post-TKI: 43.0% (58/135) vs 25.2% (34/135), P=0.001). Patients with a pre-TKI T790M mutation (N=32) showed shorter progression free survival (PFS) and overall survival (OS) than patients without a T790M mutation (N=77) (9.2 vs 12.7 months, P=0.004; and 19.3 vs 31.9 months, P=0.001, respectively). No differences were observed in post-TKIPFS or OS (12.5 vs 12.2 months, P=0.744; and 27.0 vs 29.7 months, P=0.636, respectively). Post-treatment patients were divided into high-frequency (>4.375%) and low-frequency (≤4.375%) groups, according to the mutant T790M-to-wild-type gene ratio calculated from D-PCR results. Patients in the high-frequency group showed a significantly shorter OS than the low-frequency group (20.67 vs 29.13 months, P=0.009).

      Conclusion
      D-PCR is more sensitive than ARMS in detecting the T790M mutation. The presence of a pre-TKI T790M mutation and a high frequency of post-TKI T790M mutation predicted poor outcomes of EGFR-TKI treatment.

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