Higher-dose EGFR drug, bevacizumab and spinal chemotherapy for lung cancer in the brain lining

Who can take part

• Aged ≥ 18 years at the time of signing the informed consent form, regardless of gender
• Histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), staged as IV according to the 8th edition of the IASLC TNM classification (2015)
• Presence of EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation)
• Leptomeningeal metastasis (LM) progression after standard-dose first-, second-, or third-generation EGFR-TKI treatment
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adequate major organ function, defined as: hemoglobin (Hb) ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 100 × 10\^9/L, white blood cell count (WBC) ≥ 3.0 × 10\^9/L and ≤ 10.0 × 10\^9/L; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 50 ml/min (for patients with liver metastases, TBIL ≤ 3.0 × ULN, ALT and AST ≤ 5.0 × ULN); activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤ 1.5 × ULN
• At least 21 days since the last radiotherapy (including whole-brain radiotherapy or local radiotherapy for brain metastases)
• Expected survival ≥ 3 months
• Ability to swallow oral medications (or receive crushed medications via gastrostomy tube if unable to swallow)
• For women: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) within 14 days prior to enrollment, during the study, and for 3 months after the last study drug administration
• For men: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) during the study and for 3 months after the last study drug administration
• Voluntary participation, signed informed consent, and willingness to comply with study procedures and protocols

Who cannot take part

• Major surgery within 4 weeks prior to the start of study treatment, or need for major surgery during the study
• Severe cardiovascular events within 6 months prior to enrollment, including cerebrovascular accident, deep vein thrombosis, or pulmonary embolism
• Use of drugs or supplements known to be strong inducers of CYP3A4
• Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• Active bacterial/fungal/viral infections requiring intravenous antibiotic therapy
• Drug-induced pneumonitis or interstitial lung disease, or evidence of clinically significant active pulmonary disease
• History of other systemic malignant tumors within the past 5 years (except for cured basal cell carcinoma, carcinoma in situ of the cervix, and ovarian cancer)
• Known severe allergy to any study drug or its excipients
• History of definite neurological or psychiatric disorders (including epilepsy and dementia)
• Other conditions deemed unsuitable for enrollment by the investigator
• Significant cardiovascular disease, such as New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, symptomatic arrhythmias requiring treatment, or corrected QT interval (QTcF) > 470 ms on consecutive electrocardiograms
• Pregnancy, lactation, or refusal of effective contraception by patients of childbearing potential