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C ncer de Pulm n con Mutaci n de EGFR: Un Abordaje Diferente para una Enfermedad Distinta

EGFR mutated NSCLC is a distintc disease. . Riely, et al. Clin Cancer Res 2006. Mutations identified in EGFR gene. Exons 1?16. Exons 18?24. Exons 25?28. EGFR transcript. Exon 17. . . . . . . . . Confer sensitivity/resistance to EGFR TKIs. Unclear effect on sensitivity to EGFR TKIs. 18. . . . 18. 19

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C ncer de Pulm n con Mutaci n de EGFR: Un Abordaje Diferente para una Enfermedad Distinta

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    1. Cáncer de Pulmón con Mutación de EGFR: Un Abordaje Diferente para una Enfermedad Distinta Luis Paz-Ares Hospital Universitario Virgen del Rocio Seville, Spain

    2. EGFR mutated NSCLC is a distintc disease

    3. Mutations identified in EGFR gene

    4. EGFR mutation-positive disease: a biologically distinct subtype of NSCLC

    5. Consequences of mutated EGFR

    6. EGFR mutation-positive disease: a genetically distinct subtype of NSCLC Higher incidence of changes in gene copy number in EGFR mutation-positive NSCLC1 including amplification of the mutated EGFR gene itself Lower incidence of other gene mutations in EGFR mutation-positive NSCLC2,3 no concomitant KRAS, HER2, BRAF mutations

    7. EGFR mutations induce tumours in animal models

    8. Frequency of EGFR Mutations

    9. Erlotinib in EGFR mutation+ NSCLC: Spanish Lung Cancer Group (SLCG)

    11. Overall Survival - Multivariate

    12. Previous chemotherapy did not influence survival

    13. Overview of EGFR mutated lung cancer treatment Median PFS from individual studies 90% accuracy intervals (any line of therapy)

    14. SLCG Phase III Trial in EGFR-mutated NSCLC EURTAC/GECP 06/01

    15. Better clinical outcomes for exon 19 deletions versus L858R mutation

    16. Kinetic Differences of EGFR Mutants

    17. EGFR mutation profiling into clinical practice

    18. Selection by clinical characteristics is not adequate for identifying EGFR mutations

    19. March 2005-November 2008 109 Institutions 2015 samples from NSCLC patients screened for EGFR mutation (exons 19 & 21) Median time for analysis: 7 days (5-9 days) SLADB Project

    20. Frequency of EGFR Mutations

    21. Comparison of Mutation Detection Methods

    22. Protein based Mutation Detection: ABs 2 ABs available (exon 19 E746_A750del and L858R) Covering 90% of activating mutations Sensitivity 92% Specificity 99% 100% correlation in samples with known mutational status Very sensitive, cost effective, fast method

    23. Serum-based testing for EGFR mutations Several trials have examined whether testing of circulating plasma DNA for EGFR mutations is sufficiently sensitive and consistent with testing tumour samples 80–90% correlation of results between serum and tumour sample testing probability of detecting mutation in serum likely associated with tumour burden Need to use sensitive detection method (direct sequencing not adequate) Further prospective trials planned and ongoing

    25. Erlotinib in Patients with EGFR Mutation in Serum DNA

    26. Microfluidic Chip for Sorting CTCs

    27. Gracias luis.pazares.sspa@juntadeandalucia.es

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