the Efficacy and Safety of Anlotinib Combined With Almonertinib in the First-line Treatment of Patients With Brain Metastases From EGFR Mutation-positive Non-small Cell Lung Cancer

Exclusion Criteria

• •1\) Small cell lung cancer (including lung cancer mixed with small cell carcinoma and non-small cell carcinoma); 2) Brain metastases accompanied by active bleeding; 3) Those who have previously used anti-tumor angiogenesis drugs (such as bevacizumab, endurance, anlotinib, etc.) treatment failure; 4) At the beginning of the study treatment, there was an unhealed toxic reaction of grade ≥2 (NCI-CTC AE4.03) related to the previous treatment: (except for hair loss and grade 2 neuropathy caused by platinum drugs) 5) Those who have a variety of factors that affect oral medications (such as uncontrollable nausea and vomiting, inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.); 6) Local radiotherapy to relieve the disease within 14 days before the first administration of the study treatment; radiotherapy or extensive radiotherapy for more than 30% of the bone marrow area within 4 weeks before the first administration (for palliative treatment of non-brain metastases such as bone metastases) Except for radiotherapy); 7) Patients with any severe and/uncontrolled diseases, including:
• •1. Patients with unsatisfactory blood pressure control (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• •2. Meet any of the following cardiac standards: In the resting state, the average corrected QT interval (QTcF) obtained from 3 ECG examinations is ≥470 msec (Fredericia formula is used, see Appendix 4 for details). Various clinically significant heart rhythm, conduction, and resting ECG morphological abnormalities, such as complete left bundle branch block, third-degree block, second-degree block, and PR interval ≥250 msec. Various factors that may increase the risk of QTc prolongation or the risk of arrhythmia events, such as cardiac insufficiency according to NYHA standards III to IV; heart failure; hypokalemia; congenital long QT syndrome; family history with long first-degree relatives QT syndrome or sudden death of unknown cause under 40 years of age; various combined medications that may prolong the QT interval.
• •3. Active or uncontrolled serious infection;
• •4. Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;
• •5. Poor diabetes control (fasting blood glucose (FBG)\> 10mmol/L);
• •6. Urine routine shows that urine protein is ≥++, and the 24-hour urine protein quantification is confirmed to be greater than 1.0 g; 8) Long-term unhealed wounds or fractures; 9) Pulmonary hemorrhage with NCI CTC AE grade\> Grade 1 occurred within 4 weeks before enrollment; other parts of bleeding with NCI CTC AE grade\> Grade 2 occurred within 4 weeks before enrollment; hemorrhage tendency (such as active peptic ulcer) Or patients who are receiving thrombolytic or anticoagulant therapy such as warfarin, heparin or their analogues; 10) Those who have had arterial/venous thrombotic events within 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; 11) Clinically significant hemoptysis (more than 50ml of hemoptysis per day) occurred within 3 months before enrollment; or significant clinically significant bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood at baseline ++ and above, or suffer from vasculitis, etc.; 12) Have the following past history: interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, clinically active interstitial lung disease; 13) People who have a history of psychotropic drug abuse and cannot be quit or have mental disorders; 14) Respiratory syndrome (≥CTC AE grade 2 dyspnea), severe pleural fluid, ascites, and pericardial effusion; 15) A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; active infection, such as HBV (HBV DNA copy number\> 103/ml), HCV, HIV, etc.; 16) According to the judgment of the investigator, those with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.
• •17\) The patient has active ingredients or inactive excipients, chemical structure and AZD9291 (and/or anlotinib) to AZD9291 (and/or anlotinib) A history of hypersensitivity to drugs similar to / or Anlotinib or AZD9291 (and/or Anlotinib).
• •18\) Men or women who have fertility but have not taken effective contraceptive measures, women are pregnant or breastfeeding, or have a positive pregnancy test (urine or serum) before entering the study.
• •19\) Because the patient is unwilling to comply with the research procedures, restrictions and requirements, the researcher determines that the patient should not participate in the research.
• •20\) Allogeneic bone marrow transplantation has been performed. 21) Any serious or uncontrolled eye disease may increase the safety risk of the patient according to the judgment of the investigator; 22) In the 120 days before the collection of genetic samples, whole blood without leukocytes was transfused; 23) The patient has other coexisting malignant tumors or has been diagnosed with other malignant tumors in the last 5 years, except for basal cell carcinoma, cervical or squamous cell skin cancer in situ, and papillary thyroid carcinoma.