We aim to compare the efficacy and safety of double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus double Dose of Third-generation EGFR-TKI in patients with leptomeningeal progression following the treatment of routine dose of EGFR-TKI,
Age 18 years at the time of signing informed consent, both sexes;
advanced or metastatic NSCLC, TNM stage IV according to the eighth edition of IASLC 2015;
with EGFR sensitive mutation (exon 19 deletion or L858R mutation), LM progression after conventional doses of three generation EGFR targeted agents (after 1 + 3,2 + 3 or direct 3-generation targeted therapy). There is no limit on the number of chemotherapy lines. The enrolled patients required brain parenchyma and extracranial lesion stable
ECOG PS score: 0-3
Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the study program;
Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)
patient with active bacterial infection, fungal infection (intravenous antibiotics required at initiation of study treatment);
past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid therapy, Or any signs of clinically active interstitial lung disease;