title: Incidence and risk of hypertension associated with ramucirumab in cancer patients: A systematic review and meta-analysis.
abstract: BACKGROUND
  Ramucirumab, a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), has been approved for the treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma. Hypertension has been described as a common adverse event with ramucirumab, but the incidence and risk have not been well determined. We conduct this meta-analysis to investigate the overall incidence and risk of developing hypertension associated with use of ramucirumab.
  
  
  METHODS
  Databases from PubMed, Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) meeting up to May 31, 2014, were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating ramucirumab in cancer patients with adequate data on hypertension. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% confidence intervals (CIs) by using either random--effect or fixed--effect models according to the heterogeneity of included studies.
  
  
  RESULTS
  A total of 2,649 patients with a variety of solid tumors from eight prospective clinical trials were included in our analysis. The incidence of all--grade and high-grade hypertension associated with ramucirumab was 16.4% (95%CI: 11.9-22.3%) and 9.8% (95%CI: 7.2-13.0%), respectively. Patients treated with ramucirumab had a significantly increased risk of developing all-grade (RR: 2.28, 95%CI: 1.61-3.24, P < 0.001) and high-grade (RR: 3.59, 95%CI: 2.32-5.53, P < 0.001) hypertension compared with patients treated with control medication. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  The use of ramucirumab is associated with a significantly increased risk of developing hypertension when compared with controls. Close monitoring and appropriate managements are recommended during the therapy.
authors.affiliation: Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Pudong New District, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.affiliation: Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Pudong New District; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Pudong New District, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Pudong New District; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Guo
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D015994:Incidence; D009369:Neoplasms / Q000150:complications*; D016017:Odds Ratio; D017594:Publication Bias; D012306:Risk; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000096662:Ramucirumab