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A. Ryska



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    MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI16.02 - Rare and Common EGFR Mutations in Patients with Advanced NSCLC Treated with EGFR-TKIs: A Registry-Based Study (ID 2775)

      16:45 - 18:15  |  Author(s): A. Ryska

      • Abstract
      • Presentation
      • Slides

      Background:
      Erlotinib, gefitinib and afatinib, tyrosine kinase inhibitors directed at EGFR signalling (EGFR-TKI), are currently used for the treatment of patients with advanced-stage non-small cell lung cancer (NSCLC). A considerable progress in the field of molecular oncology and cancer genomics in recent years has let to identification of several gene alterations predicting clinical outcome of patients treated with EGFR-TKIs. Activating EGFR mutations are widely recognized predictors of good response to EGFR-TKI treatment. While the predictive role of common EGFR mutations (exon 19 deletions and exon 21 L858R point mutation) is well described, very little clinical evidence data exist on the role of rare EGFR mutation types. The aim of this study was to assess the distribution of common and rare EGFR mutations in patients with NSCLC and to evaluate the efficacy of EGFR-TKIs for patients harboring rare and common EGFR mutations.

      Methods:
      Clinical data of 305 patients with advanced-stage NSCLC (IIIB or IV) treated with EGFR-TKIs having EGFR mutation positive primary tumors at the time of diagnosis were evaluated in a retrospective setting. The therapy included erlotinib, gefitinib or afatinib as recorded in a Czech national lung cancer registry – TULUNG. The relative frequency and survival data (PFS and OS) were evaluated for individual EGFR mutation types.

      Results:
      The common activating EGFR mutations (exon 19 deletion and exon 21 L858R point mutation) were found in a total of 249 (81.6%) patients. Rare EGFR mutations were found in 56 (18.4%) patients, the most frequent of which was exon 18 - G719X mutation found in 29 patients (9.5%), followed by mutations in exon 20 found in 28 patients S768I in 3 patients (0.98%) and insertion 3 mutations in 16 patients (5.2%). Patients with exon 19 deletion had median median OS 11.0 months, patients with exon 21 point mutation L858R median OS 9.4 months,respectively. Patients with rare EGFR mutations median OS 12.5 months.Comparing frequent and rare mutations, there were no differences in sex, age, PS, stage of disease and adverse effects of first line gefitinib therapy, the group of patients with rare mutations were more frequently smokers, duration of gefitinib therapy was shorter, response rate and PCR, PFS and OS were worse than in patients having frequent EGFR mutations. There were no significant differences in characteristics, PFS and OS between exon 19 deletion and exon 21 L858R point mutation tumour patients.

      Conclusion:
      While patients with frequent EGFR sensitive mutations have significant benefit from gefitinib therapy, patients with G719X mutation on exon 18 have marginal PFS and OS benefit, while pagtients with exon 20 insertion mutations have no demonstrable benefit from targeted therapy.Next generation tyrosinkinase inhibitors may prolong survival in some of rare EGFR mutated tumour patients.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-045 - Insights into NSCLC Molecular Testing in Central and Eastern European Countries (ID 2615)

      09:30 - 17:00  |  Author(s): A. Ryska

      • Abstract
      • Slides

      Background:
      Information is lacking about molecular testing practices for NSCLC in Central and Eastern Europe; identification of the challenges for personalized lung cancer treatment within this region might facilitate strategies to overcome these and to improve patient care.

      Methods:
      A Working Group of oncologists, pulmonologists and pathologists from Central and Eastern Europe was established in order to get more information about NSCLC molecular testing used in these countries, technologies, patient selection, availability and other questions, and to raise greater awareness of the current issues around personalized medicine for lung cancer in this region. As a first step, a questionnaire including 37 questions about issues connected with NSCLC molecular testing and other aspects of NSCLC management was distributed in 2014 to 59 specialists in different areas of NSCLC, including epidemiologists, oncologists, pulmonologists and pathologists.

      Results:
      In all, 25 experts from 9 countries (Bulgaria, Croatia, Czech Republic, Hungary, Israel, Poland, Slovakia, Slovenia, Turkey) responded. The responses show that there are some differences between the countries in the region and also between centers within countries with regard to NSCLC molecular testing. Some are minor, e.g. for EGFR mutation testing real-time PCR is used in all countries, direct sequencing in 5, and other methods are used in addition in only 2 countries. Up to one-quarter of samples are inadequate for testing. For ALK testing, IHC followed by FISH and/or FISH alone are currently used in all 7 countries with responses; in Israel, other methods including DNA sequencing are also used. However, some of the differences are quite large, such as the proportion of eligible patients tested for EGFR mutations and ALK rearrangements, and the proportion of NSCLC patients discussed at multidisciplinary tumor boards. There is also wide variation in funding sources for EGFR and ALK testing.

      Conclusion:
      NSCLC molecular testing is available in all Central and Eastern European countries participating in this survey. For the future, ensuring adequate NSCLC samples, solving sustainable financing of molecular testing and enabling wide access of eligible patients to molecular testing resulting in raising the number of patients reviewed by multidisciplinary boards are among the key challenges.

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