Gefitinib Combined With Chemotherapy or Antiangiogensis in Patients With Bim Deletion or Low EGFR Mutation Abundance

Inclusion Criteria:

* Histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer, anti-cancer treatment naiive
* EGFR exon 19 deletion or exon 21 L858R.
* Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than 4.9%, for L858R less than 9.5%.
* ECOG performance status of ≤ 1.
* Patients must have measurable disease according to the RECIST (version 1.1) criteria.
* Life expectancy of at least 12 weeks
* Written (signed) informed Consent to participate in the study.
* Adequate organ function as defined by the following criteria:

Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.

Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl.

Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).

* For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.

Exclusion Criteria:

* Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments.
* Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
* Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.
* Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.
* lactating women
* Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
* Unwilling to write informed consent to participate in the study or unwilling to receive follow-up
* Tumor invade big vessels or close to big vessels (less than 5mm)
* Obvious cavity or necrosis formed in the tumor, Uncontrolled hypertension, Myocardial ischemia or infarction more than stage II, cardiac insufficiency. Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy
* Hemoptysis, more than 2.5ml daily
* Thrombosis in 12 months, including pulmonary thrombosis, stoke, or deep venous thrombosis.
* Unhealed bone fracture or wound for long time