Author of

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

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

  • 12406

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    P3.02-020 - NSCLC Molecular portrait of the sample of Czech population and indications of targeted therapy (ID 3119)

    09:30 - 09:30  |  Author(s): O. Fiala
    • Abstract

    Background
    Molecular therapy targeted on tumour driving mutations should improve quality of life, PFS and overal survival in NSCLC patients. While EGFR mutations are widely accepted as targets for gefitinib and erlotinib in the first line treatment of advanced NSCLC, recently, translocation of EML4-ALK as well as amplification of ROS1, are used as guides for indication of crizotinib. Some other genetic changes, such as EGFR amplification, c-Met amplification, PIK3CA mutations and KRAS mutations are expected to serve as prognostic or predictive factors of targeted therapy currently or in near future.

    Methods
    We analyzed molecular predictors which were routinely tested at our department starting in 2004. We focus on EGFR mutations, EGFR gene amplifications, KRAS mutations, EML4-ALK translocations, c-Met amplifications and PIK3CA mutations. We analyzed the frequency of genetic changes and , where applicable, their impact on PFS and OS. We have also analysed comparability of PCR based detection (multiplex ligation-dependent probe amplification, MLPA) an FISH for EGFR gene amplifications.

    Results
    In the group of 890 NSCLC patients we found EGFR mutations on exon 19 in 62 cases, EGFR mutations on exon 21 in 24 patients. KRAS mutations were found in 141/819. Translocations of EML4-ALK were found in 7/203, c-Met amplifications in 5/104, EGFR amplifications in 11/34 and PIK3CA mutations in 8/220 patients. We confirmed a high correlation between FISH and MLPA-based testing of EGFR amplifications, as well as agreement of PFS and OS of both groups. However, EGFR gene amplifications were not prognostic, nor predictive marker of TKI therapeutic efficacy. Positive predictors of such treatment were in accordance with the literature and our expectiations, EGFR mutations for the treatment with gefitinib and erlotinib, and EML4-ALK translocations for crizotinib. We identified KRAS G12C mutation as the only negative predictor of EGFR inhibitor treatment. One hundred patients were defined as triple negative tumors (EGFR, EML4-ALK, KRAS negative). Some of our patiens had some combinations of genetic changes, such as concurrent EGFR and KRAS mutations, mutations and amplifications of EGFR gene and, in one patient, mutations and amplifications of EGFR, EML4-ALK translocation and c-Met amplification.

    Conclusion
    Precious morphologic and genetic investigations of NSCLC tumour tissue should serve as a guide for targeted therapy. However, in our population of non-squamous tumour lesions, we found predominantly a triple negative tumour type which should continue to be treated by first line chemotherapy.