| Eligibility |
Inclusion Criteria:
1. Voluntarily sign informed consent;
2. Non-squamous non-small cell lung cancer, newly diagnosed or previously not treated
with systemic chemotherapy and / or epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitors treatment;
3. Aged 18-75 years;
4. Eastern Cooperative Oncology Group (ECOG) score = 2;
5. Survival is expected to exceed 12 weeks ;
6. Patients had a wild-type genotype (WT population; patients with EGFR or ALK genetic
alterations were excluded)
Exclusion Criteria:
If any of the following criteria is met, the subject shall be excluded:
1. Squamous cell carcinoma (including adenosquamous carcinoma) and small cell lung cancer
(including small cell carcinoma and non-small cell mixed lung cancer);
2. In the past 2 weeks, there have been systematic anti-tumor treatment including
chemotherapy (including thoracic chemotherapy), radiotherapy (excluding radiotherapy
of metastatic lesions outside the thoracic radiation field), targeted therapy,
immunotherapy and biotherapy;
3. The subject had received anti-vascular endothelial growth factor (VEGF) small molecule
tyrosine kinase inhibitors or monoclonal antibodies in the past 4 weeks;
4. Laboratory results:
- White blood cell count <3 × 109 / L, neutrophil count <1.5 × 109 / L, platelet
<75 × 109 / L, or hemoglobin <8g / dL;
- Coagulation abnormalities (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds
or activated partial thromboplastin time (APTT) > 1.5 ULN), with bleeding
tendency or being treated with thrombolysis or anticoagulation;
- Serum total bilirubin =1.5 ULN; alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) = 2.5 ULN in the absence of liver metastases; ALT or AST
=5 ULN in liver metastases;
- Serum albumin <30g / L;
- Serum creatinine = 1.5 ULN or creatinine clearance <40ml / min; • Urine routine
urinary protein = ++, or 24 hours urine protein = 1.0 g;
5. Heart disease with significant clinical symptoms, such as: congestive heart failure,
coronary heart disease with symptom, arrhythmia hardly be controlled by drugs,
myocardial infarction in 6 months, or heart failure;
6. Imaging (CT or MRI) showed a tumor lesion 5 mm away from the large vessels, or the
presence of invasive central vasculature of the central tumor; imaging (CT or MRI)
showed significant cavitation or necrosis of the lung tumor; Other diseases that may
cause haemoptysis;
7. Imaging (CT or chest radiograph) showed significant pneumothorax, fluid pneumothorax;
8. Obvious cough blood in 6 months, or daily hemoptysis amounted to half a teaspoon
(2.5ml) or more;
9. Significant bleeding symptoms or with definite bleeding tendency within 12 months
before randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer,
occult blood ++ and above, intracerebral hemorrhage, vasculitis, or with congenital or
acquired coagulopathy disorders;
10. Thrombosis, cancer thrombosis (including arteriovenous thrombosis, tumor thrombus,
pulmonary embolism, transient ischemic attack, etc.) occurred within 12 months;
11. There are gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative
colitis and other gastrointestinal diseases or other diseases may cause
gastrointestinal bleeding or perforation;
12. Severe respiratory diseases, or need long-term oxygen, corticosteroid treatment of
diseases such as chronic obstructive pulmonary disease, interstitial lung disease and
respiratory failure;
13. Patients with uncontrolled central nervous system metastasis;
14. There are serious uncontrolled systemic diseases, such as nephrotic syndrome,
infection, poorly controlled diabetes;
15. Patients with active HIV(human immunodeficiency virus), HBV(hepatitis B virus), or
HCV(hepatitis C virus) infection;
16. Patients had undergone surgery (<28 days) or did not heal completely, or had other
unhealed wounds before the study;
17. Patients known to be allergic to bevacizumab or any of the components of the drug;
18. Pregnant or lactating female patients, or unwilling to take contraceptive measures of
reproductive age patients (including men);
19. There is a serious psychological or mental abnormality, or lack of compliance;
20. The investigator determines other circumstances that may affect the conduct of
clinical studies and the determination of findings;
21. Participants with an active, known or suspected autoimmune disease;
22. Participants with a condition requiring systemic treatment with either corticosteroids
or other immunosuppressive medications within 14 days of first treatment;
23. Participants with interstitial lung disease that is symptomatic or may interfere with
the detection or management of suspected drug related pulmonary toxicity.
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