Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3518 - Molecular heterogeneity assessment by NGS in non-small cell lung cancer (NSCLC) harboring EGFR mutations: results of the French Cooperative Thoracic Intergroup (IFCT) Biomarkers France study.

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Hélène Blons

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

H. Blons1, J. Oudart2, J. Merlio3, S. Hominal4, F. de Fraipont5, D. Debieuvre6, F. Escande7, C. Audigier Valette8, P. Bringuier9, S. Moreau Fraboulet10, L. Ouafik11, D. Moro-Sibilot12, A. Lemoine13, A. Langlais14, P. Missy15, F. Morin15, P. Souquet16, F. Barlesi17, J. Cadranel18, M. Beau-Faller19

Author affiliations

  • 1 Biochimie Uf De Pharmacogénétique Et Oncologie Moléculaire, APHP, HEGP, 75015 - Paris/FR
  • 2 Biochimie Uf De Pharmacogénétique Et Oncologie Moléculaire, APHP, HEGP, Paris/FR
  • 3 Ea 2406 Histologie Et Pathologie Moléculaire Des Tumeurs, Université de Bordeaux, Bordeaux/FR
  • 4 Service Cancérologie-oncologie, Centre Hospitalier Annecy Genevois, 74370 - Metz-Tessy/FR
  • 5 Molecular Genetic, Oncology, CHU Grenoble Alpes, 38000 - Grenoble/FR
  • 6 Service De Pneumologie, Hôpital Emile Muller, GHRMSA, 68100 - Mulhouse/FR
  • 7 Centre Biologie Et Pathologie, CHRU Lille, 59000 - Lille/FR
  • 8 Service De Pneumologie, Hospital Sainte Musse, 83100 - Toulon/FR
  • 9 Centre De Biologie Et Pathologie Est, Service D'anatomie Et De Cytologie Pathologique, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon/FR
  • 10 Pneumologie, Hopital Foch, 92151 - Suresnes/FR
  • 11 Service De Transfert D'oncologie Biologique, APHM, Marseille/FR
  • 12 Thoracic Oncology Unit, CHU de Grenoble, La Tronche/FR
  • 13 Biochimie Et Oncogénétique, Hopital Paul Brousse, Villejuif/FR
  • 14 Department Of Biostatistics, IFCT, Paris/FR
  • 15 Clinical research Unit, IFCT, 75009 - Paris/FR
  • 16 Service De Pneumologie, Centre Hospitalier Lyon Sud, 69495 - Pierre Bénite/FR
  • 17 Service D'oncologie Multidisciplinaire Et Innovations Thérapeutiques, Aix-Marseille Université; Assistance Publique Hôpitaux de Marseille, 13015 - Marseille/FR
  • 18 Service De Pneumologie, Hôpital Tenon GH-HUEP, 75020 - Paris/FR
  • 19 Laboratoire De Biologie Moléculaire & Plate-forme De Génomique Des Cancers D’alsace, Hôpital de Hautepierre & Institut Régional du Cancer, 67200 - Strasbourg/FR
More

Resources

Abstract 3518

Background

NSCLC is characterized by genome alterations that promote cancer cell growth. TO what extent co-mutations cooperate with the EGFR driver and explain the variable response to EGFR TKI is not well understood. Here, we screened additional co-mutations (ACMs) and evaluate their clinical impact in patients (pts) with advanced NSCLC.

Methods

We identified 204 pts with EGFR mutated tumors from the IFCT Biomarkers France study cohort with available tumor DNA who received first or second line first-generation EGFR-TKIs. Samples were assessed by NGS using the AmpliSeq Cancer Hotspot Panel v2. Among the 204 samples, 167 were fully contributive.

Results

EGFR mutations were: classical with del 19 (74; 44%) and L858R (59; 35%), complex (17; 10%) including T790M (9; 5%) or uncommon (17; 10%). EGFR was amplified in 27 (17%) samples. ACMs were identified in 120 (72%) samples with an average of mutations at 2.9 (2-8). Recurrent ACMs (more than 6 samples) were in TP53 (84; 50.3%), CTNNB1 (16; 10%), PI3KCA (15; 9%), RB (12; 7%), APC (10; 6%), PTEN (8; 5%) and ATM (7; 4.5%). EGFR complex mutations were more frequent in smokers (p = 0.01) whereas RB1 mutations were more frequent in non-smokers (p = 0.03). CTNNB1 mutations were mutually exclusive with TP53 (p = 0.01) or PI3KCA (p = 0.05) mutations. High EGFR variant allelic fraction was associated to EGFR amplification (p < 0.001) suggesting mutant allele amplification and to TP53 mutations (p = 0.003). Non-classical or complex EGFR mutations were linked to rapid (< 3 months) versus normal (3-20 months)/slow (> 20 months) progression (p = 0.07 and p = 0.05 respectively). In the non-T790M group, ATM and PTEN mutations were negative predictors of first-line TKI efficacy (mPFS 3.7 versus 8.9 months, HR 2.85, 95CI% 1.14-7.15 and mPFS 5.6 versus 9.0 months, HR 2.46, 95CI% 1.16-5.9, respectively).

Conclusions

EGFR mutated NSCLC have heterogeneous molecular profiles. This work suggests that PTEN and ATM mutations could limit EGFR inhibitor efficacy. However, large series of EGFR mutated NSCLC will be needed to validated links between clinical outcomes and specific EGFR altered pathways.

Clinical trial identification

Legal entity responsible for the study

IFCT.

Funding

AstraZeneca: INCa (French NCI); IFCT (Alain Depierre Research Award 2015).

Editorial Acknowledgement

Disclosure

D. Debieuvre: Consulting: Roche; Honoraria: AstraZeneca, Chugaï, Lilly, Roche, Novartis, Pfizer, MSD, BMS; Grants: Roche, AstraZeneca, Lilly, BMS, Boehringer Ingelheim, Chiesi, Chugaï, Janssen, Pfizer, MSD, Novartis, GSK, Sandoz; Board: Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis; Conferences: Roche, Boehringer Ingelheim, Novartis, Pierre Fabre, Pfizer, MundiPharma, BMS. C. Audigier Valette: Clinical trials (PI): AstraZeneca, Boehringer Ingelheim, BMS, Novartis, Roche; Consulting: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, MSD, Pfizer, Roche; Conferences: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, Pfizer, Roche. S. Moreau Fraboulet: Personal fees and non-financial support: Novartis; Non-financial support: Lilly. D. Moro-Sibilot: Personal fees: Roche, Eli Lilly, Pfizer, Novartis, AstraZeneca, BMS, MSD, Boehringer Ingelheim. A. Lemoine: AstraZeneca, Boehringer, Roche. F. Barlesi: Personal fees: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer. J. Cadranel: Clinical research (PI): AbbVie, AstraZeneca, Bayer, Boehringer–Ingelheim, BMS, MSD, Novartis, Roche, Takeda; Consulting: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, MSD, Pfizer, Roche; Conferences: AstraZeneca, BMS, MSD, Pfizer. M. Beau-Faller: Board: BMS, Boehringer-Ingelheim, AstraZeneca; Non-financial support: AstraZeneca, Roche. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings