CSF CTC-Capture-Guided EGFR-TKI and Bevacizumab Combination Therapy in EGFR-Mutant Advanced NSCLC

Inclusion Criteria:

* 1.The subjects voluntarily joined this study and signed the informed consent form, showing good compliance and cooperation with follow-up.

  2.Ages between 18 years old (inclusive) and 75 years old (inclusive). 3.ECOG score: 0-2 points. 4.Expected survival of no less than 3 months. 5.According to the RECIST 1.1 criteria, the patient has at least one extracranial target lesion.

  6.Diagnosed with non-small cell lung cancer based on histology or cytology. 7.No leptomeningeal metastasis (EANO criteria). 8.The tumor tissue samples or blood samples are confirmed to have EGFR-sensitive mutations (including exon 19 deletions or L858R).

  9.Have not received systemic anti-tumor treatment, and are planned to receive first-line monotherapy with osimertinib, aumolertinib, or furmonertinib.

  10.The main organ functions are normal, that is, they meet the following criteria:
  1. The standard for routine blood test should meet: HB≥90 g/L; ANC≥1.5×10\^9/L; PLT≥80×10\^9/L.
  2. The biochemical examination should meet the following standards: TBIL\<1.5×ULN; ALT and AST\<2.5×ULN; serum Cr≤1.25×ULN or endogenous creatinine clearance \> 45 ml/min (Cockcroft-Gault formula). 11.Women of childbearing age must have taken reliable contraceptive measures and have undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate methods of contraception during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization.

Exclusion Criteria:

1. Subjects have received any of the following treatments:

   1. Previously used any EGFR tyrosine kinase inhibitors;
   2. Previously received any chemotherapy for lung cancer;
   3. Previously received any radiotherapy for lung cancer (except for palliative radiotherapy for bone metastases);
   4. Within 4 weeks before the first administration of the study medication, the subject had undergone major surgery;
   5. Within 7 days before the first administration of the study medication, used strong inhibitors or inducers of CYP3A4.
2. Subjects with concurrent other malignant tumors, except for basal cell carcinoma of the skin and in situ cancer.
3. Subjects have uncontrollable malignant pleural effusion and pericardial effusion.
4. Subjects who are allergic to contrast agents used in CT and MRI or who cannot tolerate MRI examinations.
5. As judged by the investigator, there are any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding diathesis, or active infection.
6. Clinically severe gastrointestinal dysfunction that may affect the intake, transport, or absorption of medication, such as the inability to take oral medication, uncontrollable nausea or vomiting, a history of extensive gastrointestinal resection, untreated recurrent diarrhea, atrophic gastritis, gastric diseases requiring long-term use of proton pump inhibitors that have not been cured, Crohn's disease, ulcerative colitis, etc.
7. Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
8. Meet any of the following cardiac examination results:

   1. The average value of the corrected QT interval (QTcF) derived from three electrocardiograms (ECG) at rest using the Fridericia formula is \> 470 msec;
   2. Resting ECG indicates conduction or ECG morphological abnormalities (such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, and PR interval \> 250 msec, etc.);
   3. There are any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication of unexplained sudden death in direct relatives under 40 years old or prolonged QT interval;
   4. The left ventricular ejection fraction (LVEF) is \< 50%.
9. Insufficient bone marrow reserve or organ function, meeting any of the following laboratory limits:

   1. Absolute neutrophil count \<1.5×10\^9/L;
   2. Platelet count \<100×10\^9/L;
   3. Hemoglobin \<90 g/L (\<9 g/dL);
   4. If there is no clear liver metastasis, alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN); if there is liver metastasis, ALT \> 5×ULN;
   5. If there is no clear liver metastasis, aspartate aminotransferase (AST) \> 3×ULN; if there is liver metastasis, AST \> 5×ULN;
   6. If there is no clear liver metastasis, total bilirubin \> 1.5×ULN; or with Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total bilirubin \> 3×ULN;
   7. Creatinine \> 1.5×ULN and creatinine clearance \<50 mL/min (calculated by the Cockcroft-Gault formula); creatinine clearance is only required to be confirmed if creatinine \> 1.5×ULN;
   8. Serum albumin (ALB) \<28 g/L.
10. Active fungal, bacterial, and/or viral infections requiring systemic treatment.
11. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
12. History of interstitial lung disease, drug-induced interstitial lung disease, history of radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
13. Subjects judged by the investigator to be likely non-compliant with the study procedures and requirements, such as those with a clear history of neurological or psychiatric disorders, or currently suffering from psychiatric disorders.
14. Subjects judged by the investigator to have any conditions that may endanger the subject's safety or interfere with the study assessment.