38P High-dose aumolertinib in EGFR-mutant NSCLC with leptomeningeal metastases: A real-world study focusing on poor prognostic subgroups

Background: Leptomeningeal metastasis (LM) following treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) poses a significant challenge in the clinical management of advanced EGFR-mutated non-small cell lung cancer (NSCLC).This study aimed to evaluate the efficacy and safety of EGFR-TKIbased regimen combined with intrathecal chemotherapy in EGFR-mutated NSCLC patients (pts) with LM who had previously been treated with EGFR-TKIs.Methods: This retrospective, real-world study enrolled pts with histologically or cytologically confirmed EGFR-mutated NSCLC who developed LM after disease progression following previous treatment with EGFR-TKIs.Pts were treated with EGFR-TKI-based regimen combined with intrathecal methotrexate or pemetrexed as enhanced therapy.The primary endpoint was progression-free survival of enhanced therapy (PFS2).Secondary endpoints included correlation analysis between changes in cerebrospinal fluid (CSF) cell count and survival benefit, intracranial symptom status relief in LM pts, and the time from initial EGFR-TKI treatment to LM.Results: 55 EGFR-mutated pts were enrolled.The median age was 59 years, and 25 were female.EGFR mutation subtypes included 19Del (n=19), L858R (n=27), uncommon mutation (n=9)(3 were 20ins mutation and 6 were PACC mutation).The median follow-up time was 31.93 months, the median PFS2 was 9.56 months.In subgroup analysis, median PFS2 was 22.93 months for 19Del, 9.56 months for L858R, and 1.07 months for uncommon mutation.Pts with a post-treatment CSF cell count of <10, 10-100 and 100 had a median PFS2 of not reached, 8,38 and 3.27 months.Intracranial symptoms improved in 22 patients.Among pts who had previously received EGFR-TKIs, the median time from initial EGFR-TKI treatment to LM development was 30.98 months.All pts were well-tolerated and no new safety signals were observed. Conclusions:The EGFR-TKI-based regimens combined with intrathecal chemotherapy demonstrated improved progression-free survival and intracranial symptom relief in EGFR-mutated NSCLC pts with LM.CSF cell count may serve as a potential prognostic marker and could help guide clinical decision-making.