Anlotinib Hydrochloride Combined With EGFR-Tyrosine Kinase Inhibitor (TKI) in Treating Advanced NSCLC Patients With Acquired Resistance to EGFR-TKI

Exclusion Criteria

• •Small cell lung cancer (including Small cell lung cancer mixed with non-small cell lung cancer);
• •Imaging (CT or MRI) showed that the distance between the lesion and the large vessels was less than 5 mm, or there were central tumors invading the local large vessels, or there were obvious pulmonary cavity or necrotic tumors.
• •Patients with active brain metastasis, cancerous meningitis, spinal cord compression, or with brain or pia mater diseases detected by CT or MRI at screening time (patients with stable symptoms and complete treatment 14 days before enrollment may be admitted to the group, but no symptoms of cerebral hemorrhage should be confirmed by craniocerebral MRI, CT or venography evaluation).
• •Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥ 90 mmHg, despite using the optimal medical treatment;
• •Patients are participating in other clinical studies, or there are less than four weeks before the end of the previous clinical study.
• •Other active malignant tumors requiring concurrent treatment;
• •The patient has a history of malignant tumors. Patients with basal cell carcinoma of skin, superficial bladder cancer, squamous cell carcinoma of skin or carcinoma of cervix in situ who had undergone possible curative treatment and had no disease recurrence within 5 years after the initiation of curative treatment are permitted.
• •Patients had treatment related adverse reactions after previous systemic anti-tumour therapy (except hair loss), but did not recover to NCI-CTCAE ≤ 1 grade.
• •The patient has the coagulation disorders (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or activated partial thromboplastin time (APTT) \> 1.5 ULN), or bleeding tendency, or undergoing thrombolysis or anticoagulation therapy; Note: On the premise that the International Standardized Ratio of Prothrombin Time (INR) is less than 1.5, low doses of heparin (0.6 million to 12,000 U per day for adults) or aspirin (less than 100 mg per day) are allowed for preventive purposes.
• •Renal insufficiency: Urinary routine indicated that urinary protein ≥ ++ or confirmed 24-hour urinary protein ≥ 1.0 g;
• •Subjects who had undergone major surgery or had severe trauma had less than 14 days before enrollment.
• •Severe acute or chronic infections requiring systemic treatment
• •Severe cardiovascular diseases: grade II or above myocardial ischemia or myocardial infarction and poor control arrhythmias (including corrected QT interval (QTc) interval ≥ 450 ms for males and ≥ 470 ms for females); cardiac insufficiency of grade III to IV according to New York Heart Association (NYHA) criteria, or left ventricular ejection fraction (LVEF) \< 50% by color Doppler echocardiography;
• •≥ CTCAE grade 2 peripheral neuropathy, except for trauma.
• •Respiratory syndrome (≥ CTCAE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
• •Long-term unhealed wound or fracture;
• •Decompensated diabetes mellitus or other contraindications of high-dose glucocorticoid therapy;
• •There are obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
• •Three months prior to enrollment, significant hemoptysis (more than 50 ml per day) occurred, or significant clinical hemorrhage symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ or above, or suffering from vasculitis.
• •Arteriovenous thrombosis events occurred within 12 months before enrollment, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism.
• •Patients participated in clinical trials of other antineoplastic drugs within four weeks prior to enrollment, or planned systemic anti-tumor therapy within four weeks prior to enrollment or during the period of the study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or use of mitomycin C within six weeks prior to the treatment of the experimental drugs). Over-extended-field radiotherapy (EF-RT) was performed within four weeks prior to grouping or limited-field radiotherapy to evaluate the tumor lesions was performed within two weeks prior to grouping;
• •Physical and laboratory findings Untreated active hepatitis (hepatitis B: HBsAg positive and hepatitis B virus (HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis C virus (HCV) RNA positive and abnormal liver function); co-infection of hepatitis B and hepatitis C;
• •According to the researcher's judgment, patients may have other factors that may lead to the forced termination of the study, such as other serious diseases or serious abnormal laboratory examinations or other factors that may affect the safety of the subjects, or family or social factors such as test data and sample collection.