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