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.

ABSTRACT:

Background

Diagnosis 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.

Methods

EGFRm + 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.

Results

Twenty-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 p

SUBMITTER: van der Wel JWT 

PROVIDER: S-EPMC11630515 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature