title: The effect of anti-angiogenic agents on overall survival in metastatic oesophago-gastric cancer: A systematic review and meta-analysis.
abstract: BACKGROUND
  Studies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed outcomes. We undertook systematic review and meta-analysis to determine their overall benefits and harms.
  
  
  METHODS
  Randomized controlled trials in mOGC were sought investigating the addition of AAs to standard therapy (best supportive care or chemo). The primary endpoint was overall survival (OS) with secondary endpoints progression-free survival (PFS), overall response rate (ORR) and toxicity. Estimates of treatment effect from individual trials were combined using standard techniques. Subgroup analyses were performed by line of therapy, region, age, performance status, histological type, number of metastatic sites, primary site, mechanism of action and HER2 status.
  
  
  RESULTS
  Fifteen trials evaluating 3502 patients were included in quantitative analysis. The addition of AAs was associated with improved OS: HR 0·81 (95% CI 0·75-0·88, p<0·00001) and improved PFS: HR 0·68 (95% CI 0·63-0·74, p<0·00001). Subgroup analyses favoured greater benefit for OS in 2nd/3rd line settings (HR 0·74) compared to 1st-line settings (HR 0·91) (X2 = 6·00, p = 0·01). OS benefit was seen across all regions-Asia (HR 0·83) and rest of world (HR 0·75)-without significant subgroup interaction. Results from 8 trials evaluating 2602 patients were pooled for toxicity > = Grade 3: with OR 1·39 (95% CI 1·17-1·65).
  
  
  CONCLUSIONS
  The addition of AAs to standard therapy in mOGC improves OS. Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting. Consistent OS benefit was present across all geographical regions. This benefit is at the expense of increased overall toxicity.
authors.affiliation: Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: David L
authors.identifier: http://orcid.org/0000-0002-7773-3144
authors.initials: DL
authors.lastname: Chan
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.|Department of Medical Oncology, Cancer Care Centre, St George Hospital, Sydney, New South Wales, Australia.
authors.forename: Katrin M
authors.initials: KM
authors.lastname: Sjoquist
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Department of Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Martin
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.affiliation: Department of Oncology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.affiliation: Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018734:Genes, erbB-2; D006801:Humans; D017594:Publication Bias; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents