AI Article Synopsis

  • The study investigates the challenges of diagnosing and treating leptomeningeal metastases (LM) in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) who are being treated with osimertinib, focusing on identifying resistance mechanisms in cerebrospinal fluid (CSF) and plasma.
  • A group of 28 patients was analyzed, with a high detection rate of the driver mutation in CSF, but resistance mechanisms were found in 27%, indicating limitations in treatment options available at this time.
  • After four weeks on an escalated osimertinib dosage, many patients showed stabilization or worsening of symptoms, suggesting that while some had radiological improvement, overall clinical efficacy remains

Article 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 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.

Conclusions: In 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630515PMC
http://dx.doi.org/10.1093/neuonc/noae138DOI Listing

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