title: Implications of bevacizumab discontinuation in adults with recurrent glioblastoma.
abstract: BACKGROUND
  Patients with recurrent glioblastoma benefiting from bevacizumab are often treated indefinitely due to concerns regarding rebound tumor recurrence upon discontinuation. However, treatment is discontinued for reasons other than disease progression in a subset of these patients, the characteristics and outcomes of which are poorly defined.
  
  
  METHODS
  Of 342 adults with recurrent glioblastoma in our database treated with bevacizumab, 82 received treatment for ≥ 6 months; of these, bevacizumab was discontinued for reasons other than tumor progression in 18 patients (Bev-D) and for disease progression in the remainder (Bev-S). The impact of discontinuation on outcome was assessed with discontinuation as a time-dependent covariate in a Cox hazards model for progression-free survival.
  
  
  RESULTS
  There was no difference in hazard rates for progression between Bev-D and Bev-S groups; the adjusted hazard ratio for progression using discontinuation as a time-dependent covariate was 0.91 (95% CI:0.47, 1.78). The median PFS after bevacizumab-discontinuation was 27 weeks (95% CI:15-NR). At progression, a higher proportion of Bev-D patients had local progression compared with the Bev-S patients. Salvage therapy in Bev-D patients yielded a PFS-26 weeks of 47% (95% CI:23%-94%) with a median PFS of 23 weeks (95% CI:12-NR), vs. 5% (95% CI: 1%-21%) and 9 weeks (95% CI: 6-11) in Bev-S patients (HR:0.3;CI, 0.1-0.6) (P = .0007).
  
  
  CONCLUSIONS
  Bevacizumab discontinuation unrelated to disease progression does not appear to cause rebound recurrence or worsen PFS in patients who benefit from bevacizumab. Additionally, Bev-D patients had an improved response to salvage therapy, findings which provide a strong basis for a prospective study.
authors.affiliation: Department of Neuro-Oncology (M.A., M.H., V.P.); Department of Biostatistics (K.H.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Anderson
authors.affiliation: Department of Neuro-Oncology (M.A., M.H., V.P.); Department of Biostatistics (K.H.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Hamza
authors.affiliation: Department of Neuro-Oncology (M.A., M.H., V.P.); Department of Biostatistics (K.H.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.affiliation: Department of Neuro-Oncology (M.A., M.H., V.P.); Department of Biostatistics (K.H.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: bevacizumab; discontinuation; glioblastoma; outcome; recurrence