1. PTEN, ATM, IDH1 mutations and MAPK pathway activation as modulators of PFS and OS in patients treated by first line EGFR TKI, an ancillary study of the French Cooperative Thoracic Intergroup (IFCT) Biomarkers France project
- Author
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Blons, H., Oudart, J.-B., Merlio, J.-P., Debieuvre, D., De Fraipont, F., Audigier-Valette, C., Escande, F., Hominal, S., Bringuier, P-P, Fraboulet-Moreau, S., Ouafik, L., Moro-Sibilot, D., Lemoine, A., Langlais, A, Missy, P., Morin, F., Souquet, P.-J., Barlesi, F., Cadranel, J., Beau-Faller, M, Bringuier, P.‐P., Beau‐Faller, M., Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,MAPK/ERK pathway ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,IDH1 ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Ataxia Telangiectasia Mutated Proteins ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Genotype ,medicine ,Humans ,PTEN ,In patient ,Protein Kinase Inhibitors ,Molecular profiles ,biology ,business.industry ,PTEN Phosphohydrolase ,Ancillary Study ,Prognosis ,medicine.disease ,EGFR mutations ,Isocitrate Dehydrogenase ,3. Good health ,ErbB Receptors ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Next-generation sequencing ,biology.protein ,Adenocarcinoma ,France ,KRAS ,business ,Biomarkers - Abstract
Objectives Tumor mutation screening is standard of care for patients with stage IV NSCLC. Since a couple of years, widespread NGS approaches used in routine diagnostics to detect driver mutations such as EGFR, KRAS, BRAF or MET allows the identification of other alterations that could modulated the intensity or duration of response to targeted therapies. The prevalence of co-occurring alterations that could affect response or prognosis as not been largely analyzed in clinical settings and large cohorts of patients. Thanks to the IFCT program “Biomarkers France“, a collection of samples and data at a nation-wide level was available to test the impact of co-mutations on first line EGFR TKI in patients with EGFR mutated cancers. Materials and methods Targeted NGS was assessed on available (n = 208) samples using the Ion AmpliSeq™ Cancer Hotspot Panel v2 to screen for mutations in 50 different cancer genes. Results This study showed that PTEN inactivating mutations, ATM alterations, IDH1 mutations and complex EGFR mutations were predictors of short PFS in patients with a stage 4 lung adenocarcinoma receiving first line EGFR TKI and that PTEN, ATM, IDH1 and KRAS mutations as well as alterations in the MAPK pathway were related to shorter OS. Conclusion These findings may lead to new treatment options in patients with unfavorable genotypes to optimize first line responses.
- Published
- 2021