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. (January 2021)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Lung cancer. Volume 151(2021)
• Page Start: 69
• Page End: 75
• Publication Date: 2021-01
• Subjects: Non-small cell lung cancer -- Next-generation sequencing -- EGFR mutations -- Molecular profiles -- Prognosis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.11.008
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Response to EGFR TKI is heterogeneous among patients with EGFR mutated NSCLC. Routine use of NGS enables co-mutations detection that may impact response to treatment. Complex EGFR mutations are linked to reduced PFS and OS in patients with NSCLC. MAPK activation is linked to reduced OS in patients with EGFR mutated NSCLC. PTEN, ATM and IDH1 mutations are linked to low PFS and OS in patients with EGFR mutated NSCLC. 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.