Apatinib in the Treatment of Patients With EGFR T790M-Negative NSCLC

Inclusion Criteria:

* Pathologically confirmed stage IIIB, IV non-squamous non-small cell lung cancer, with measurable lesions (the long axis of tumor lesions ≥ 10mm with CT, the short axis of lymph node lesions ≥ 15mm with CT, the lesions not receive radiotherapy, frozen or other local treatment);
* Patients with slow progression on first-line EGFR TKI(erlotinib / icotinib / gefitinib) treatment;
* No T790M mutation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy;
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
* Life expectancy of more than 3 months;
* Adequate bone marrow function: WBC ≥ 3.0 ×10 E+9/L, neutrophil ≥ 1.5 × 10 E+9/L, platelets ≥ 80 × 10E+9/L,Hb ≥ 10.0g/dL;a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL), a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤3UNL or ≤5UNL in case of liver metastasis, a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault);
* Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug;
* the participants volunteered to join this study should sign the informed consent forms, have better compliance in the follow-up;

Exclusion Criteria:

* Squamous cell carcinoma (including adenosquamous carcinoma); Small cell lung carcinoma (including small cell carcinoma and non-small cell mixed lung carcinoma);
* Active brain metastases, cancerous meningitis, patients with spinal cord compression;
* Rapid progression of the disease or cancer invades vital organs;
* The distance between the tumor lesion and the large blood vessel is less than 5 mm, or there is a central tumor invading local macrovascular;
* obvious pulmonary cavity or tumor necrosis;
* Uncontrollable high blood pressure;
* Grade Ⅱ or above myocardial ischemia or myocardial infarction or arrhythmia control is not good,Ⅲ \~ Ⅳ grade cardiac insufficiency, or cardiac ultrasonography showed left ventricular ejection fraction (LVEF) \<50% according to the NYHA standard;
* Have a history of interstitial lung disease or patients with interstitial lung disease;
* Coagulation abnormalities (INR\> 1.5 or PT\> ULN + 4s or APTT\> 1.5 ULN) with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
* There was significant hemoptysis within 2 months prior to enrollment, or a daily hemoptysis volume is 2.5 ml or above;
* A clinically significant bleeding symptom or bleeding tendencies such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above, or vasculitis that occurred within 3 months prior to enrollment;
* Aneurysm / venous thrombotic events such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
* Arterial / venous thrombotic events such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months prior to enrollment;
* Hereditary or acquired bleeding and thrombophilia, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism；
* Long-term unhealed wounds or fractures;
* Major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;
* Unable to swallow, chronic diarrhea or intestinal obstruction;
* Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months prior to enrollment;
* Urinary protein ≥ ++, 24-hour urinary protein ≥ 1.0 g;
* Active infections require antimicrobial treatment;
* ALK gene abnormalities (gene fusion or mutation occurred);
* Pregnant or lactating women, or women unwilling or unable to take effective contraception;