Author of

• 11543

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  P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11589

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    P2.06-046 - EML4-ALK monitoring of crizotinib response in blood platelets and plasma of NSCLC patients (ID 3267)

    09:30 - 09:30  |  Author(s): J. Nilsson
    • Abstract

    Background
    The discovery of various genetic alterations that underlie lung cancer has opened-up a new era in the development of specifically targeted therapies employing specific alteration-dependent inhibitors. In the vast majority of NSCLC patients genetic alterations occur in EGFR (20-25%), BRAF (3%), and ALK (3-10%), seemingly in a predominant mutual exclusive manner. Hence, patient stratification for EGFR, KRAS, BRAF, and ALK alterations is becoming common practice among oncologists. The mutational status of NSCLC patients is considered dynamic and can change in due course of the disease and selection in response to therapy. Longitudinal monitoring of the mutational status of NSCLC patients is of crucial importance to tailor targeted therapy by adapting treatment regimens according to mutational status. However, technical challenges associated with serial tumor biopsy constitute a major challenge in longitudinal molecular monitoring and targeted treatment of NSCLC patients. Blood-based assays may overcome such limitations and allow for frequent assessment of the mutational status.

    Methods
    Here, tumor tissue, platelets, and/or plasma of NSCLC patients were collected and analyzed for the presence of translocated ALK using FISH, IHC, and/or RT-PCR. Monitoring of EML4-ALK in platelets and plasma was performed by RT-PCR on EML4-ALK positive patients treated with crizotinib and correlated to the clinical response as measured by serial radiographic CT.

    Results
    From a multicenter cohort of NSCLC patients we identified EML4-ALK positive patients by FISH, IHC, and RT-PCR, for blood platelet and/or plasma isolation. In blood platelets of ALK positive NSCLC patients (n=24) and ALK negative control subjects (n=54) we demonstrated an EML4-ALK test sensitivity of 70-80% and specificity of 100%. We detected EML4-ALK in plasma of ALK positive NSCLC patients (n=22), however with inferior sensitivity of 20-30%. In addition, longitudinal EML4-ALK monitoring in blood platelets of an ALK positive NSCLC patient correlated with the crizotinib response.

    Conclusion
    We demonstrate here that blood platelets of NSCLC patients are a biosource for the detection of the EML4-ALK translocation and may proof useful for longitudinal monitoring of ALK inhibitors in NSCLC patients, with superior outcome over plasma.