4.5 Article

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

期刊

LUNG CANCER
卷 151, 期 -, 页码 69-75

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2020.11.008

关键词

Non-small cell lung cancer; Next-generation sequencing; EGFR mutations; Molecular profiles; Prognosis

资金

  1. French Cooperative Thoracic Intergroup (IFCT): Alain Depierre Award
  2. Institut National du Cancer (INCa)
  3. AstraZenaca

向作者/读者索取更多资源

Tumor mutation screening is crucial for patients with stage IV NSCLC, and identifying co-occurring alterations, such as PTEN, ATM, IDH1, and KRAS mutations, can impact the response and prognosis to first line EGFR TKI therapy. These findings may offer new treatment options for patients with unfavorable genotypes to improve their initial treatment responses.
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 AmpliSeg (TM) 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.

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