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(Abstract)

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The management of leptomeningeal metastases (LM) in patients with non-small cell lung cancer (NSCLC) remains challenging. In this study, the authors aimed to confirm the presence of LM in NSCLC patients with ALK or EGFR mutations through molecular analysis of cerebrospinal fluid (CSF). They also aimed to identify resistance mechanisms (RM) to targeted therapy (TT) in both CSF and plasma and assess the concordance of RM between the two fluid samples.<br /><br />Twenty-eight patients with EGFR-mutated NSCLC and three patients with ALK fusion-positive NSCLC were included in the study. The primary driver mutation was identified in 90% of CSF samples, with EGFR and ALK being the most common. RM was identified in CSF samples from seven EGFR-mutated NSCLC patients. In three EGFR-mutated NSCLC patients without RM in CSF, plasma sequencing identified RM in BRAF and PIK3CA. No RM was identified in ALK CSF or plasma samples.<br /><br />Treatment with osimertinib dose escalation (DE) was prescribed for EGFR-mutated NSCLC patients, while lorlatinib was prescribed for ALK fusion-positive NSCLC patients. Clinical and radiological assessment after four weeks of osimertinib DE showed improvement in some patients, stabilization in others, and deterioration in some. For ALK fusion-positive NSCLC patients, one patient showed partial response, one had stable disease, and one had progressive disease on MRI.<br /><br />The study concludes that while the primary driver mutation can be identified in the majority of NSCLC patients with LM, identifying RM to targeted therapy in CSF remains challenging. Commonly identified RM in systemic progression were not found in CSF or plasma. Consequently, therapeutic options after osimertinib failure are limited, with DE providing only temporary solutions with limited clinical benefit.<br /><br />In summary, this study highlights the difficulties in identifying RM in LM and the limitations of current therapeutic options for NSCLC patients with LM and resistance to targeted therapy.

Asset Subtitle

Tijmen van der Wel

Meta Tag

Speaker Tijmen van der Wel

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

leptomeningeal metastases

non-small cell lung cancer

NSCLC

ALK mutation

EGFR mutation

cerebrospinal fluid analysis

resistance mechanisms

targeted therapy

osimertinib dose escalation

lorlatinib