title: Incidence and risk of proteinuria with aflibercept in cancer patients: a meta-analysis.
abstract: BACKGROUND
  Aflibercept is a human recombinant fusion protein with antiangiogenic effects that functions as a decoy receptor to bind vascular endothelial growth factor A. Proteinuria is one of its major adverse effects with a substantial variation in the incidence rate, and the overall risk of proteinuria has not been systematically studied. We performed a meta-analysis of published clinical trials to quantify the incidence and relative risk of proteinuria in cancer patients treated with aflibercept.
  
  
  METHODS
  The electronic databases were searched, including PubMed, Embase, Cochrane databases, and ASCO (American Society of Clinical Oncology) abstracts. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity data on proteinuria. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies.
  
  
  RESULTS
  A total of 4,596 patients with a variety of solid tumors from 16 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade proteinuria in cancer patients were 33.9% (95% CI: 27.3-42.1%) and 7.9% (95% CI: 6.1-10.2%). The relative risks of proteinuria of aflibercept compared to control were increased for all-grade (RR = 1.41, 95% CI: 1.13-1.77) and high-grade (RR = 6.18, 95% CI: 3.78-10.12) proteinuria. The risk of developing all-grade and high-grade proteinuria with aflibercept was substantially higher than that of bevacizumab (all-grade: RR 1.85, 95% CI: 1.63-2.11; high-grade: RR 2.37, 95% CI: 1.84-3.05).
  
  
  CONCLUSIONS
  Aflibercept is associated with an increased risk of developing proteinuria. Appropriate monitoring and treatment is strongly recommended to prevent potential renal damage. Future studies are still needed to investigate the risk reduction and possible use of aflibercept in cancer patients.
authors.affiliation: Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Radiation, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Ye
authors.affiliation: Zhejiang Food and Drug Administration, Hangzhou, Zhejiang Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Danna
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D011507:Proteinuria / Q000139:chemically induced* / Q000453:epidemiology* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor