Rh-Endostatin in Combination With Icotinib for Advanced NSCLC With EGFR Mutations

Inclusion Criteria:

* Histologic documentation of non small cell lung cancer, with activating epidermal growth factor receptor (defined as deletion 19 or exon 21 L858R mutation).
* Stage IV disease according to the 7th Edition of the American Joint Committee on Cancer staging system -Measureable disease
* Life expectancy of \>= 12 months
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* Absolute neutrophil count (ANC) \>= 1, 500/mm\^3, platelet count \>= 100,000/mm\^3, hemoglobin \>= 9.0 g/dL.
* Total bilirubin =\< 1.5 x upper limit of normal (ULN), serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN in patients without liver or bone metastases; \< 5 x ULN in patients with liver or bone metastases, cockcroft-Gault calculated creatinine clearance of \>= 45 ml/min or creatinine =\< 1.5 x ULN.
* Prothrombin time (PT) =\< 1.5 x ULN, partial thromboplastin time (PTT) =\< ULN
* Urine dipstick proteinuria \< 2+. Patients discovered to have \>= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours.
* Negative pregnancy test done =\< 7 days prior to randomization, for women of childbearing potential only.
* Provide informed written consent.
* Willing to return to enrolling institution for follow-up.
* Willing to provide tissue and blood samples for correlative research purposes.

Exclusion Criteria:

* Evidence of bleeding diathesis or coagulopathy.
* Evidence of central nervous system involvement or brain metastases confirmed by head CT or brain MRI within 28 days prior to being registered for protocol therapy.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for protocol therapy.
* Anticipation of need for major surgical procedure during the course of the study.
* Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to registration for protocol therapy.
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration for protocol therapy.
* Serious, non-healing wound, ulcer, or bone fracture.
* History of hemoptysis.
* Clinically significant infections as judged by the treating investigator.
* Other active malignancy