title: Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma.
abstract: BACKGROUND
  Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically.
  
  
  METHODS
  We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease.
  
  
  RESULTS
  There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%.
  
  
  CONCLUSIONS
  Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Iwamoto
authors.forename: L E
authors.initials: LE
authors.lastname: Abrey
authors.forename: K
authors.initials: K
authors.lastname: Beal
authors.forename: P H
authors.initials: PH
authors.lastname: Gutin
authors.forename: M K
authors.initials: MK
authors.lastname: Rosenblum
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
authors.forename: L M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: A B
authors.initials: AB
authors.lastname: Lassman
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012189:Retrospective Studies; D016879:Salvage Therapy; D017211:Treatment Failure
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab