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Age 18 years old, gender unlimited |
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NSCLC was confirmed by histology or cytology, and it was evaluated as stage IIIB-IV local advanced, recurrent or metastatic patients who could not be treated surgically. Note: the diagnosis result of NSCLC based on sputum cytology needs to be confirmed by immunohistochemistry; the current disease should be treated by radiotherapy as the first choice The subjects whose treatment strategy or follow-up target focus judged by the researchers should take radiotherapy as the first treatment strategy should not be selected |
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No systemic anti-tumor therapy was received for locally advanced, recurrent or metastatic NSCLC |
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According to the method of second-generation sequencing, L858R point mutation in exon 21 of EGFR gene was found in primary NSCLC with or without any other coexisting mutations |
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Within 28 days before randomization, at least one measurable lesion was selected according to the RECIST v1.1 standard (see Appendix 1); for the lesions that had previously received radiotherapy, only when there was clear disease progression 3 months after the end of radiotherapy, can they be selected as target lesions |
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ECoG general condition score is 0-1 (see Appendix 2) |
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Expected survival 12 weeks |
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Patients receiving radiotherapy can be included in the group if they meet the following conditions |
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There was no history of lung disease radiotherapy within 28 days before |
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randomization; L. for radiotherapy outside the chest area, the interval from |
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the end of final radiotherapy to at least 28 days before randomization, and |
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all toxic reactions have recovered |
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\. Good blood function within 14 days before randomization |
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L. the absolute neutrophil count (ANC) was 1.5 109 / L (without the support of |
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granulocyte colony stimulating factor) and; L lymphocyte count 0.5 109 / L |
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and; 1. Platelet count 100 109 / L and; Hemoglobin 9 g / dl (in order to reach |
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this standard, patients can receive blood transfusion) |
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\. Good liver function within 14 days before randomization: L) total |
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bilirubin 1.5 upper normal limit (ULN) and |
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Ast, ALT and ALP of patients without liver metastasis were less than 2.5 ULN; ast, ALT and ALP of patients with liver metastasis were less than 5 ULN |
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Good renal function within 14 days before randomization |
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Serum creatinine 1.5 ULN or calculated creatinine clearance 45 ml / min and; The urine test paper of urine protein was less than 2 +. If the baseline urine analysis of proteinuria patients is 2 +, 24-hour urine sample collection must be completed, and 24-hour urine protein 1 g; serum albumin 25 g / L |
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Within 14 days before randomization, INR 1.5 ULN, APTT 1.5 ULN. 13. Heart function meets the requirement of left ventricular ejection fraction (LVEF) 50% |
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Fertile women: during the treatment period and within 6 months after the last administration, they agreed to abstinence (no heterosexual sexual intercourse) or use contraceptive methods (contraceptive methods with a failure rate of less than 1%). If a postmenopausal woman has not reached the postmenopausal state (menopausal time 12 months, no other reason except menopause) and has not undergone sterilization (removal of ovaries and / or uterus), she is defined as a woman with fertility |
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Male: for male patients with fertility of female partners or pregnancy of female partners, they agree to abstinence (no heterosexual sexual intercourse) or use condoms within 6 months after the last administration, and agree not to donate sperm |
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Sign the informed consent voluntarily. 17. The researchers judged that they could comply with the research plan |
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\- |
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Histology or cytology confirmed mixed adenocarcinoma with squamous cells as the main component (the proportion of squamous cells 10%)
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There was a history of malignancy (except NSCLC) in the first 5 years before randomization, except for malignancies with negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as cervical carcinoma in situ, non melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ or stage I uterine cancer, which were treated appropriately
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Previous hypertensive crisis, hypertensive encephalopathy, or uncontrolled hypertension (blood pressure: systolic pressure > 150 mmHg and / or diastolic pressure > 100 mmHg)
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The tumor invades the main blood vessels. Researchers or local radiologists must rule out evidence that the tumor is completely adjacent to, surrounding, or extending into the lumen of a major artery, such as the pulmonary artery or superior vena cava
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Any other disease, neurological or metabolic dysfunction; medical examination or laboratory finding that a disease or condition is suspected, which prohibits the use of the test drug or exposes the patient to a high risk of treatment-related complications
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It is highly suspected that there are patients with idiopathic pulmonary fibrosis, organic pneumonia, drug-related pneumonia, idiopathic pneumonia, active pneumonia or active tuberculosis
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Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently) allows patients to retain catheters
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History of hereditary bleeding constitution or coagulation disorder or other evidence of increased bleeding risk
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There are non healing wounds, active ulcers or fractures
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Patients with tracheoesophageal fistula, gastrointestinal perforation or gastrointestinal fistula, and intraperitoneal abscess in the first 6 months were randomly assigned
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Cardiovascular diseases with clinical significance (such as active), including but not limited to TIA (within 6 months before screening), myocardial infarction (within 6 months before screening), unstable angina, congestive heart failure with New York Heart Association classification level II (see Appendix 3), and serious arrhythmias beyond the control of drugs
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Within 3 months before randomization, there was a history of hemoptysis 2 levels, that is, the blood volume of each bleeding event was > 2.5ml
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Evidence of central nervous system metastasis, except for patients without any symptoms or patients with symptoms but stable condition, at least 28 days after treatment of central nervous system metastasis
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Major surgery (including open biopsy) or severe trauma was performed within 28 days prior to randomization, or was expected to be performed during study treatment
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Severe infections occurring within 28 days prior to randomization, including
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but not limited to hospitalization for complications of infection, bacteremia
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or severe pneumonia
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aspirin (325 mg / day) or other non steroidal anti-inflammatory drugs known
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to inhibit platelet function are currently or recently used (within 10 days
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before bevacizumab was first used)
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full dose oral or parenteral anticoagulants or thrombolytic agents are
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currently or recently used (within 10 days prior to the first use of
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bevacizumab). Preventive use of anticoagulants is permitted
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\. Core biopsies or other minor operations were performed within 7 days
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prior to randomization, but vascular access devices were not included
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Vascular access devices should be placed at least 2 days before the start of
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study treatment
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\. Those who are known to be allergic to bevacizumab, gefitinib and their
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excipients, or to Chinese hamster ovarian cell products or other recombinant
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human or humanized antibodies
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\. Those who were confirmed to be HCV positive, HIV positive, syphilis
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positive, or HBsAg positive during the screening period, and whose HBV DNA
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titer in the peripheral blood was 1000 copies / L
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\. Pregnancy or lactation, or pregnancy planning during the study. 22. Those
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who participated in any other clinical trial and took the trial drug treatment
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within 30 days before randomization
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\. The investigator determined that the risk of the subject was greater than
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any other benefit
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