The goal of this clinical trial is to explore the efficacy and safety of double-dose third-generation EGFR-TKI combined with bevacizumab and intrathecal chemotherapy in treating advanced non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis that progressed after prior standard-dose third-generation EGFR-TKI treatment. It also aims to investigate the correlation between cerebrospinal fluid genetic characteristics and prognosis as well as subsequent efficacy prediction in patients with leptomeningeal metastasis after resistance to standard-dose third-generation EGFR-TKI. The main questions it intends to answer are: Does this combined treatment regimen improve leptomeningeal metastasis response rate (LM-ORR) evaluated by RANO-LM? What adverse events occur in patients during the treatment with this combined regimen? Researchers will conduct a single-arm phase II prospective study to assess the effectiveness and safety of the combined treatment, without a control group comparison. Participants will: Receive double-dose third-generation EGFR-TKI (osimertinib 160mg qd, furmonertinib 160mg qd, or almonertinib 220mg qd) + intrathecal pemetrexed (induction phase: 10mg twice a week for 4 weeks; maintenance phase: 10mg once a week for 4 weeks; consolidation phase: 30mg every 4 weeks until disease progression or intolerable toxicity) + bevacizumab 7.5mg/kg. Undergo screening assessments within 28 days before enrollment, including tumor imaging, laboratory tests, and cerebrospinal fluid examination. During the treatment period, conduct regular checkups and tests (such as blood routine, blood biochemistry, electrocardiogram, and imaging examinations) according to the protocol (once every 4 weeks in the first two treatment cycles, then once every 8 weeks). Complete quality of life assessment using the QLQ-C30 scale every 4 weeks and record changes in neurological symptoms and ECOG scores.
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LM-ORR
Timeframe: Up to 30 days after the last study drug administration (for safety and response assessment), and through study completion, an average of 1 years (for survival follow-up)