title: Bevacizumab-induced hypertension is a predictive marker for improved outcomes in patients with recurrent glioblastoma treated with bevacizumab.
abstract: BACKGROUND
  Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor and is approved for the treatment of patients with recurrent glioblastoma (GBM). Previous authors have reported differential response to bevacizumab on an individual basis. Bevacizumab-induced hypertension is a well-documented side effect, and some reports have suggested this occurrence to be related to treatment outcome in other cancers. In the current study, the authors analyzed patients with recurrent GBM who were treated with bevacizumab based on whether the patients developed drug-induced hypertension.
  
  
  METHODS
  All patients with GBM treated within the Emory Healthcare system from 2007 through 2012 were reviewed. A total of 82 patients were identified who received bevacizumab for the treatment of recurrent GBM and were included in the current study. Patients were classified as normotensive or hypertensive depending on whether hypertension developed that was attributable to therapy. Progression-free survival (PFS) and overall survival (OS) were graphed by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards method.
  
  
  RESULTS
  The median follow-up was 19.7 months. Of the 82 patients with recurrent GBM who were treated with bevacizumab, 30 developed drug-induced hypertension. The median time to the development of hypertension was 21 days. The median PFS for the normotensive and hypertensive groups were 2.5 months (95% confidence interval [95% CI], 1.6-3.0 months) and 6.7 months (95% CI, 4.6-10.0 months), respectively (P<.001). The median OS times for the normotensive and hypertensive groups were 4.9 months (95% CI, 4.4-6.8 months) and 11.7 months (95% CI, 9.0-20.5 months), respectively (P<.001).
  
  
  CONCLUSIONS
  Patients with recurrent GBM who developed bevacizumab-induced hypertension demonstrated significantly better PFS and OS compared with normotensive individuals. Bevacizumab-induced hypertension may be a physiologic marker of outcome in patients with recurrent GBM.
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Jim
authors.initials: J
authors.lastname: Zhong
authors.forename: Arif N
authors.initials: AN
authors.lastname: Ali
authors.forename: Alfredo D
authors.initials: AD
authors.lastname: Voloschin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.forename: Ian R
authors.initials: IR
authors.lastname: Crocker
authors.forename: Hui-Kuo G
authors.initials: HK
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: Avastin; bevacizumab; differential survival; glioblastoma; hypertension