Pneumologie 2019; 73(S 01)
DOI: 10.1055/s-0039-1678021
Posterbegehung (P03) – Sektion Pneumologische Onkologie
NSCLC metastasiert, molekulare Treiber
Georg Thieme Verlag KG Stuttgart · New York

Frequency and clinical impact of atypical EGFR mutations in lung adenocarcinoma

Authors

  • N Magios

    1   Thoraxklinik Heidelberg

  • M Kirchner

    2   Institute of Pathology, Heidelberg University Hospital

  • P Christopoulos

    3   Thoraxklinik Heidelberg, Translational Research Center Heidelberg, German Center for Lung Research (Dzl)

  • F Bozorgmehr

    4   University Hospital Heidelberg, Thoraxklinik, Department of Thoracic Oncology

  • AL Volckmar

    5   Pathologisches Institut

  • V Endris

    6   Institute of Pathology, Heidelberg University Hospital

  • CP Heußel

    7   Diagnostische und Interventionelle Radiologie, Thoraxklinik Heidelberg

  • FJF Herth

    8   University Hospital Heidelberg, Institute of Internal Medicin III – Pneumology, Thoraxklinik

  • H Winter

    9   Thoraxklinik Heidelberg gGmbH, Abteilung für Thoraxchirurgie, Universitätsklinikum Heidelberg

  • T Muley

    10   University Hospital Heidelberg, Thoraxklinik, Translational Research Unit

  • M Meister

    10   University Hospital Heidelberg, Thoraxklinik, Translational Research Unit

  • F Lasitschka

    11   Institut für Pathologie, Universität Heidelberg

  • HG Bischoff

    12   University Hospital Heidelberg, Thoraxklinik at Heidelberg

  • P Schirmacher

    13   Universitätsklinikum Heidelberg, Institut für Pathologie

  • A Stenzinger

    13   Universitätsklinikum Heidelberg, Institut für Pathologie

  • M Thomas

    4   University Hospital Heidelberg, Thoraxklinik, Department of Thoracic Oncology
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Publikationsverlauf

Publikationsdatum:
19. Februar 2019 (online)

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    Background Most patients with EGFR-driven NSCLC harbor exon 19 deletions or exon 20 L858R point mutations, which have established sensitivity to tyrosine kinase inhibitors (TKI) with a median overall survival (OS) of several years. However, the outcome of patients with other EGFR alterations is variable and not well-defined.

    Patients and Methods We retrospectively analyzed the clinical course of TKI-treated NSCLC patients at our institution (n = 303).

    Results In total, “rare” EGFR point mutations were detected in 33 cases (11%), nine of which harboured compound mutations (3%). Most atypical EGFR mutations affected exons 18 (n = 12 or 36%, mostly G719X) and 21 (n = 14 or 42%, mostly L891Q), while mutations of exons 19 (n = 3) and 20 (n = 4) were less frequent. Overall survival (OS) did not differ by the affected exon (p = 0.58) and was 13 months in median, significantly shorter than the survival of patients with exon 19 deletions (59% of cases with 31 months median OS) and L858R point mutations (23% of cases with 18 months median OS, p < 0.0001). Progression-free survival under TKI treatment was generally longer for exon 18 and 21 (9 and 7 months in median) than for exon 19 and 20 mutations in our cohort (3 months in median, p < 0.05). No differences in the number of metastatic sites at diagnosis of stage IV disease were noted among mutations of different exons. Within the entire cohort of EGFR+ NSCLC patients, presence of “rare” EGFR mutations correlated negatively with never-/light-smoker history (< 10 pack-years, p < 0.001) and emergence of T790M mutations at the time of TKI failure (p < 0.011), and positively with the presence of non-adenocarcinoma histologies, i.e. squamous and NOS-NSCLC (15%, p = 0.002).

    Conclusions Presence of atypical EGFR mutations is associated with heavier smoking history, non-adenocarcinoma histologies, complex, non-T790 M-mediated resistance mechanisms at the time of TKI failure and shorter overall survival in EGFR+ NSCLC.