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Translational research

3719 - Ultrasensitive detection of EGFR T790M mutation by droplet digital PCR (ddPCR) in TKI naïve non-small cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide program Biomarkers France of the French Cooperative Thoracic Intergroup (IFCT).

Date

09 Sep 2017

Session

Translational research

Presenters

Michèle Beau-Faller

Citation

Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363

Authors

C. Leduc1, E. Pencreach2, J. Merlio3, P. Bringuier4, F. de Fraipont5, F. Escande6, A. Lemoine7, O. L'Houcine8, H. Blons9, M. Denis10, P. Hofman11, R. Lacave12, S. Melaabi13, A. Langlais14, P. missy15, F. Morin15, F. Barlesi16, D. Moro-Sibilot17, J. Cadranel18, M. Beau-Faller19

Author affiliations

  • 1 Chest Department, Centre Hospitalier Universitaire de Strasbourg, Nouvel Hôpital Civil, 67098 - Strasbourg/FR
  • 2 Laboratoire D’oncobiologie – Plateforme De Génétique Moléculaire Des Cancers, Centre Hospitalier Universitaire de Strasbourg, Strasbourg/FR
  • 3 Department Of Biology And Pathology, Centre Hospitalier Universitaire de Bordeaux, Pessac/FR
  • 4 Laboratoire D’anatomie Pathologique, Centre De Biologie Est, Hospices Civils de Lyon, Lyon/FR
  • 5 Biochimie Des Cancers Et Biothérapies, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche/FR
  • 6 Laboratoire De Biochimie Et Biologie Moléculaire, CHRU de Lille, Lille/FR
  • 7 Biochimie Et Oncogénétique Inserm Umr-s 1193, Hôpital Paul Brousse - Hôpitaux Universitaires Paris-Sud, Villejuif/FR
  • 8 Service De Transfert D’oncologie Biologique, APHM, Marseille/FR
  • 9 Department Of Biochemistry, Pharmacogenetics And Molecular Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 10 Molecular Biology, CHU Nantes, 44093 - Nantes/FR
  • 11 Laboratory Of Clinical And Experimental Pathology, University of Côte d'Azur, Nice/FR
  • 12 Service D’histologie, Embryologie, Cytogénétique Biologie Tumorale Et Génétique Moléculaire, APHP, Hôpital Tenon, Paris/FR
  • 13 Service De Génétique - Unité De Pharmacogénomique, Institut Curie, Paris/FR
  • 14 Biostatistic Department, French Cooperative Thoracic Intergroup, Paris/FR
  • 15 Clinical Research Unit, French Cooperative Thoracic Intergroup, 75009 - Paris/FR
  • 16 Multidisciplinary Oncology & Therapeutic Innovations, Aix Marseille University - Assistance Publique des Hôpitaux de Marseille, Marseille/FR
  • 17 Thoracic Oncology, CHU Grenoble - Hopital Michallon, 38043 - La Tronche/FR
  • 18 Service De Pneumologie, APH, Tenon University Hospital, 75020 - Paris/FR
  • 19 Laboratory Of Biochemistry And Molecular Biology, Centre Hospitalier Universitaire de Strasbourg, Hôpital de Hautepierre, Strasbourg/FR
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Abstract 3719

Background

The presence of T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies performed in small cohorts suggest that T790M was also detected in TKI-naïve NSCLC. Here, we use an ultra-sensitive ddPCR to address the incidence and clinical significance of T790M in a larger cohort of TKI-naïve NSCLC.

Methods

We analyzed 343 EGFR mutated patients of IFCT Biomarkers France program with available tumor DNA that were finally treated by EGFR-TKI. ddPCRTM was performed with QX200 system (BIO-RAD®, Hercules, USA). All samples were tested in duplicate. Colon cancers DNA were used negative controls.

Results

ddPCR identified a T790M mutation in 23/256 specimens (9%). T790M Fractional Abundance (FA) was ≥10%; ≥1%

Conclusions

Ultrasensitive detection of T790M is related in 9% of EGFR mutated TKI naïve NSCLC patients and has a negative prognostic value for T790M FA over 10%.

Clinical trial identification

NCT01700582

Legal entity responsible for the study

French Cooperative Thoracic Intergroup (IFCT)

Funding

Institut National du Cancer (INCa), AstraZeneca, IFCT (Alain Depierre Award 2015)

Disclosure

P-P. Bringuier: Research funding from Institut National du Cancer (INCa) and honoraria from AstraZeneca, Roche. F. Barlesi: Honorarium from Bristol-Myers Squibb. D. Moro-Sibilot: Personal fees from Roche, Eli Lilly, Pfizer, Novartis, AstraZeneca, Bristol-Myers Squibb, MSD, Boehringer Ingelheim. J. Cadranel: Personnal fees from AstraZeneca, Bristol-Myers Squibb and Roche for participating to board of experts. All other authors have declared no conflicts of interest.

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