efficacy and safety of use of platinum based doublet chemotherapy plus antiangiogenesis and immune checkpoint inhibitors in patients with advanced non-squamous non-small cell lung cancer

Conditions: Advanced Non-squamous Non-small Cell Lung Cancer

Summary: the purpose of this study is to explore the efficacy and safety of use of platinum based doublet chemotherapy plus antiangiogenesis and immune checkpoint inhibitors in patients with advanced non-squamous non-small cell lung cancer


Eligibility criteria:
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.