ArticleNeuro-oncology2024
Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of epidermal growth factor receptor-mutated non-small-cell lung carcinoma patients developing leptomeningeal metastases: Osimertinib Resistance Analysis-leptomeningeal metastases study.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Review
- Prognostic value of Neutrophil-to-Lymphocyte Ratio (NLR) in patients with Leptomeningeal Metastasis (LM) from solid tumors.BMC cancer · 2026Article
- Therapeutic progress in leptomeningeal metastasis from EGFR mutant non-small cell lung cancer: a clinical medicine review.Journal of cancer research and clinical oncology · 2026Review
- Decoding EGFR A289 Mutation in Glioblastoma: A Predictive Biomarker Framework and Targeted Therapeutic Insights.Journal of molecular neuroscience : MN · 2025Article
- FLAURA2: evidence for escalated first-line therapy inTranslational cancer research · 2025Article
- Advancing leptomeningeal metastases treatment inTranslational lung cancer research · 2025Article
- Liquid biopsy: Comprehensive overview of circulating tumor DNA (Review).Oncology letters · 2024Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundDiagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation-positive (EGFRm +) non-small-cell lung carcinoma (NSCLC) is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.
methodsEGFRm + patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160 mg QD) following lumbar puncture. Clinical and radiological response was evaluated 4 weeks after osimertinib DE.
resultsTwenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n = 26). Seven (27%) harbored ≥1 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in 5 patients, stabilized in 9 and worsened in 11 patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, 14 stabilization, and 3 worsening.
conclusionsIn 27% of patients, an RM was found in CSF ctDNA, none of which are targetable at the time of writing, and the clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm + NSCLC LM.
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