2023 World Conference on Lung Cancer (Posters)-P2.10. ORA-LM: Molecular Analysis in Cerebrospinal Fluid of ALK or EGFR Positive NSCLC Patients with Leptomeningeal Metastases

P2.10. ORA-LM: Molecular Analysis in Cerebrospinal Fluid of ALK or EGFR Positive NSCLC Patients with Leptomeningeal Metastases - PDF(Slides)

Back to course

Pdf Summary

Leptomeningeal metastases (LM) in patients with EGFR mutation positive NSCLC present significant challenges in identifying resistance mechanisms (RM) and finding effective treatments. This study aimed to determine if RM in the cerebrospinal fluid (CSF) can be identified and treated during osimertinib treatment.<br /><br />The study conducted simultaneous sequencing of plasma and CSF samples from patients with LM during osimertinib treatment. Driver identification was successful in 93% of CSF samples, while RM analysis was successful in 25%. The most common RM identified were ERBB2 or EGFR amplification. One patient had two secondary EGFR mutations and another had two PIK3CA mutations.<br /><br />The study concluded that CSF analysis alone cannot uncover all potential RM in LM during osimertinib treatment. Other factors that may contribute to RM include other DNA aberrations, RNA/protein aberrations, histological transformation, changes in the tumor microenvironment in the CSF, drug transporter mutations in the blood-CSF barrier, and unknown factors.<br /><br />Overall, this study highlights the difficulty in identifying and treating resistance mechanisms in patients with EGFR mutation positive NSCLC and LM. More comprehensive analysis methods incorporating various DNA and RNA aberrations, as well as consideration of other factors, may be necessary to fully understand and address resistance in these cases.

Asset Subtitle

Tijmen van der Wel

Meta Tag

Speaker Tijmen van der Wel

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

Leptomeningeal metastases

EGFR mutation positive NSCLC

resistance mechanisms

cerebrospinal fluid

osimertinib treatment

driver identification

ERBB2

EGFR amplification

secondary EGFR mutations

PIK3CA mutations