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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
- Source :
- Lung Cancer, Lung Cancer, Elsevier, 2021, 151, pp.69-75. ⟨10.1016/j.lungcan.2020.11.008⟩, Lung Cancer, 2021, 151, pp.69-75. ⟨10.1016/j.lungcan.2020.11.008⟩
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- 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
Subjects
Details
- ISSN :
- 01695002
- Volume :
- 151
- Database :
- OpenAIRE
- Journal :
- Lung Cancer
- Accession number :
- edsair.doi.dedup.....e9824b05c3c221a34bd2d0313e01a2b7