title: Effect of Combined Therapy Inhibiting EGFR and VEGFR Pathways in Non-Small-cell Lung Cancer on Progression-free and Overall Survival.
abstract: To investigate the effect of combined epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway inhibitors on progression-free survival (PFS) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC).
  
  
  
  We included 15 randomized clinical trials that had compared the combination of EGFR tyrosine kinase inhibitors and anti-VEGF/VEGFR therapy with different control groups. Pooled estimates of treatment efficacy were calculated, and subgroup analyses were conducted according to treatment line and EGFR status.
  
  
  
  Ten of 15 trials involving 3317 NSCLC patients were included. For all settings, the combined regimen demonstrated no PFS (hazard ratio [HR], 0.82; P = .10) or OS (HR, 0.97; P = .54) benefit compared with the control groups. In the first-line setting, combined therapy showed similar PFS (HR, 1.01; P = .99) but poor OS (HR, 1.36; P = .03) compared with the control groups. In the second-line or subsequent settings, combined therapy resulted in significantly longer PFS (HR, 0.75; P < .01) but similar OS (HR, 0.93; P = .16) compared with the control groups. A subgroup analysis stratified by EGFR status suggested that combined treatment substantially improved PFS (HR, 0.57; P = .04) and OS (HR, 0.45; P < .01) in patients with EGFR mutations rather than EGFR wild type.
  
  
  
  EGFR-tyrosine kinase inhibitors plus anti-VEGF/VEGFR therapy significantly prolonged PFS in the second-line treatment of NSCLC patients. An EGFR mutation is a promising indication for this combination treatment. More data are required to confirm this strategy in first-line therapy.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, People's Republic of China. Electronic address: caicunzhou_dr@163.com.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: EGFR mutation; NSCLC; Survival; Tyrosine kinase inhibitor; VEGF