A Study of Gefitinib With or Without Apatinib in Patients With Advanced Non-squamous Non-Small-Cell Lung Cancer Harboring EGFR Mutations

Inclusion Criteria:

1. ≥ 18 and ≤ 70 years of age
2. Eastern Cooperative Oncology Group(ECOG)performance scale 0 - 1.
3. Life expectancy of more than 3 weeks.
4. Histologically or cytologic confirmed，locally advanced and/or metastatic non-squamous NSCLC of stage IIIB (unsuitable for radiotherapy) or IV or recurrent NSCLC; At least one measurable lesion according to RECIST 1.1 which has not received radiotherapy or cryotherapy.
5. Documented evidence of tumor harboring an activating EGFR mutation (Example 19 del and L858R) .
6. None previous chemotherapy or targeted therapy. NOTE: neoadjuvant and/or adjuvant therapy is allowed which is completed before 6 months.
7. Prior radiation therapy is allowed if: 25% or less of total bone marrow had been irradiated,pelvis and chest had not been irradiated; at least 4 weeks have elapsed from the completion of radiation treatment, and the acute toxicity from radiation treatment had been recover; irradiated lesion is not including measurable lesions unless documented progress after radiation.
8. Adequate hepatic, renal, heart, and hematologic functions (Absolute Neutrophil Count(ANC) ≥ 1.5×109/L, Platelet (PLT) ≥ 100×109/L, Hemoglobin(HB) ≥ 100 g/L, total bilirubin within 1.5×the upper limit of normal(ULN), and serum transaminase≤2.5×the Upper Limit Of Normal(ULN), serum creatine ≤ 1 x Upper Limit Of Normal(ULN), creatinine clearance rate ≥ 50ml/min,
9. For women of child-bearing age, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative. They will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men (previous surgical sterilization accepted), will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug.
10. Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

1. Squamous cell carcinoma (including adenosquamous carcinoma, undifferentiated carcinoma); small cell lung cancer (including small cell and non-small cell mixed lung cancer)
2. Symptomatic brain metastases (Patients who have no symptoms and is not needed to receive therapy before 21 days may participate in this trial, but need to be confirmed by MRI\\CT or venography that no hematencephalon symptom);
3. Radiologically documented evidence of major blood vessel invasion or encasement by cancer; Obvious cavity or necrosis formed in the tumor.
4. Uncontrolled hypertension(systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mm Hg) even though two or more than two hypotensive agents application.
5. Patients who suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade III-IV cardiac insufficiency according to New York Heart Association(NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)\<50%;
6. History of pulmonary interstitial diseases or concurrent pulmonary interstitial diseases.
7. Coagulation disfunction（INR\>1.5 o rPT\>Upper Limit Of Normal(ULN)+4s or Activated Partial Thromboplastin Time (APTT) \>1.5 Upper Limit Of Normal(ULN)）, hemorrhagic tendency or receiving the therapy of thrombolysis or anticoagulation.
8. History of clinically significant haemoptysis =\< 2 months (more than 2.5ml or half of one tea spoon of fresh blood per day) prior to registration.
9. History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage, bleeding gastric ulcer, occult blood test ≥ (++), and vasculitis ;
10. Within 6 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack(TIA), hematencephalon, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
11. Known inherited and acquired hemorrhagic and thromboplastic possibility (such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.)
12. Long-term untreated wounds or fractures.
13. Within 4 weeks of major surgery and/or injures, fractures , ulceration.
14. Significant factors that influence the ingestion and absorption of medicine, (e.g. unable swallow, chronic diarrhea and intestinal obstruction);
15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months.
16. Urine protein≥++, or 24h urine protein quantitation≥1.0g;
17. Symptomatic serous effusion requiring treatment .(including hydrothorax, ascites, hydropericardium);
18. Active infection need antimicrobial treatments;
19. History of psychiatric drugs abuse and not be abstinent, or dysphrenia;
20. Less than 4 weeks from the last clinical trial
21. History or concomitant other malignancy except cured basal cell skin cancer, or carcinoma in situ of the cervix, or superficial bladder cancer;
22. Administration of strong/potent cytochrome P450 (CYP)3A4 inhibitors within 7 days, or inducers within 12 days;
23. Pregnant or breastfeeding women;
24. Other conditions regimented at investigators' discretion.