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D. Morales-Espinosa



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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-008 - SiRe Next Generation Sequencing Panel: Effective Diagnostic Tool for Circulating Free DNA Analysis (ID 5624)

      14:30 - 14:30  |  Author(s): D. Morales-Espinosa

      • Abstract

      Background:
      Tissue availability is a crucial point in NSCLC. The introduction of Liquid Biopsies allows to determine circulant biomarkers, specifically using free DNA. To simultaneously analyze multiple patients sample at high sensitivity, Next Generation Sequencing (NGS) can be narrowed to target a limited number of actionable genes. Here we prospectically applied a lab-developed narrowed gene panel (SiRe) to produce a DNA library covering 568 actionable mutations in six gene (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα).

      Methods:
      This daily clinical practice study was performed on cfDNA obtained from Non Small Cell Lung Cancer blood samples (serum and plasma) prospectically collected either prior to treatment administration in patients without tissue availability (n = 46) or after a progressive disease (n = 19) from a first line gefitinib (n = 14) or afatinib (n = 5) therapy.

      Results:
      SiRe detected an activating EGFR mutation in 4/46 (8.9%) cases and in T790M in 9/19 (47.4%) at the time of tumor progression. Using tissue data as gold standard, the SiRe panel showed a sensibility of 90.5% and specificity of 100%.

      Conclusion:
      The SiRe panel is an effective tool enabling the implementation of NGS for cfDNA mutational profiling in molecular pathology practice.

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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      P2.06-010 - AZD9291 as 1st-Line Therapy for EGFR Mutant NSCLC Patients with Concomitant Pretreatment EGFR T790M Mutation. The AZENT Study (ID 4267)

      14:30 - 14:30  |  Author(s): D. Morales-Espinosa

      • Abstract

      Background:
      Osimertinib (AZD9291) is a selective and irreversible pyrimidine-based inhibitor of the primary activating and the secondary EGFR mutation, T790M, which is the most common mechanism of acquired resistance to 1st and 2nd-generation EGFR tyrosine-kinase inhibitors (TKIs). Progression-free survival (PFS) with osimertinib was 9.6 and 2.8 months (m) for EGFR mutated (EGFR+) NSCLC patients progressing to prior EGFR TKI therapy with and without EGFR T790M mutation, respectively, indicating that the T790M is a predictive biomarker for osimertinib efficacy. Sixty patients from two expansion cohorts of the same study, received 1st-line osimertinib and obtained a PFS of 19.3m. T790M, arising in cis with the primary activating mutation, confers resistance to EGFR TKIs, even in the absence of drug selection. The coexistence of the pretreatment T790M mutation has been under appreciated, in spite of accumulative evidence that is present in a frequency of 35-60% using different detection methods. In our experience, pretreatment T790M mutation is frequently detected by three specific aspects of the method: tumor microdissection, examination of two separate tumor areas, and the use of a peptic nucleid acid clamp that inhibits wild-type allele amplification. Thus, we designed the first phase IIa study to evaluate the safety and efficacy of osimertinib as 1st-line therapy for patients with metastatic EGFR+ NSCLC and concomitant pretreatment T790M mutation.

      Methods:
      This is a multicenter, single-arm, open-label, non-controlled phase IIa clinical study in Spain. Eligible patients are aged ≥18 years with metastatic EGFR+ NSCLC and by central testing documented presence of pretreatment T790M mutation. Seventy-three patients will receive continuous treatment with osimertinib 80 mg daily until disease progression, intolerable adverse events, consent withdrawal or noncompliance with the study protocol. The primary endpoint is the objective response rate (ORR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The trial is designed to detect a ≥70% ORR in this patient population. Secondary objectives include PFS, overall survival, time to treatment failure, duration of response and disease control rate. Additional pre-specified secondary objectives of the study are the longitudinal analysis of EGFR mutations (including the T790M and the C797S mutations) in plasma and serum and the expression analysis of a panel of biomarkers with possible predictive value for osimertinib treatment.

      Results:
      Not applicable

      Conclusion:
      Not applicable