Due to the enrollment was slow and exceeded the expected enrollment time

Apatinib, a novel targeted inhibitor of VEGF receptor 2 (VEGFR2), shows significant antitumor activity in the patients with GC. The purpose of this study is to determine whether apatinib plus chemotherapy drug can improve progression free survival compared with chemotherapy drug in patients with metastatic the non-small cell lung cancer who failed one lines of chemotherapy.

Lung cancer is the leading cause of cancer death in world wild, especially non-small cell lung cancer (NSCLC). Detection and early intervention are difficult because pathogenesis of NSCLC is not yet entirely clear.Most of them are advanced or metastatic patients, so approach 3/4 NSCLC undergo chemotherapy. Fewer treatment options exist on NSCLC whom is wild type of EGFR. The patient did not benefit from the existing treatment regimen after first-line treatment. There is currently no effective drug to treat this group of patients.

Apatinib, a novel targeted inhibitor of VEGF receptor 2 (VEGFR2), shows significant antitumor activity in the patients with GC. The purpose of this study is to determine whether apatinib plus chemotherapy drug can improve progression free survival compared with chemotherapy drug in patients with metastatic the non-small cell lung cancer who failed one lines of chemotherapy.

Inclusion Criteria:

1. Age：18~75 years;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
3. Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC who have previously received no more than one lines treatment before participating；
4. Subjects with at least one measurable lesion as defined by RECIST (version 1.1),which is confirmed by computed tomography (CT) scan or MRI .
5. EGFRˉ,and ALK mutation in the negative or unknown；
6. Subjects without brain metastases or asymptomatic brain metastases, and not needing for dehydrating agents or corticosteroids to control intracranial symptoms;
7. Survival expectation≥ 3 months;
8. The main organ function is normal;
9. Females of childbearing potential must be a pregnancy test in 7 days before participating ( including serum or urine), and the results were negative.
10. Subjects provided written informed consent before participating,Willing and able to comply with all aspects of the protocol

Exclusion Criteria:

1. Small Cell Lung Cancer;

2. Subjects with symptomatic brain metastases;

3. Survival expectation < 3 months;

4. Blood transfusion is required in the first dose of drug treatment within 14 days ;

5. The interval of subjects had received chemotherapy, biotherapy, radiotherapy or other anticancer therapies in the first dose of drug treatment within 21 days(excluding palliative radiotherapy);

6. The risk of active bleeding;

7. Subjects with uncontrolled blood pressure with medication (140/90 mmHg)

8. Laboratory values and organ functions ： （1）Hematologic insufficiency:

   1. Hemoglobin (Hb)<8.5 g/dL，
   2. Absolute neutrophil count (ANC)≤1.5×109/L，
   3. Platelet count (PLT)< 100×109/L； （2）Insufficient liver function:
   1. Bilirubin > 1.5×the upper limit of normal (ULN)
   2. Alanine aminotransferase (ALT), or Aspartate aminotransferase (AST) >3.0×(ULN), When liver metastases,Bilirubin > 1.5×ULN, ALT or AST >5.0×(ULN.
   3. serum creatinine ≤1.0×（ULN）, or creatinine clearance > 50 mL/min( calculated per the Cockcroft and Gault formula) (3) Subjects with positive for HBV surfaceantigen ( HBsAg)or anti-hcv (4)Subjects with Interstitial lung disease (5)Insufficient renal function: serum creatinine≥ 1.5×（ULN）, or creatinine clearance <60 mL/min

9. impairment of heart function: (1)Left ventricular ejection fraction (LVEF) <45% (LVEF evaluation is not required for subjects have no history of congestive heart failure), (2)Unstable angina, (3)Severe arrhythmia, (4)NYHA III or IVgrade of congestive heart failure, (5) Subjects with miocardial infarction within the last 12 months before entering the trial, (6)Pericardial effusion,

10. Subjects with liver fibrosis or hepatic cirrhosis

11. (1)Subjects with other active malignancy (except for definitively treated non melanoma skin cancer,carcinoma in-situ of the cervix,or other cancers that are treated with curative treatment and have no signs of recurrence for at least 5 years ) , (2)Subjects with dysphagia,malabsorption,chronic gastrointestinal diseases,or other medical history may hinder compliance and / or experimental drug absorption,

12. Subjects with major surgery in the first dose of drug treatment within 28 days,

13. Subjects with positive foknown human immunodeficiency virus。