title: Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab.
abstract: Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a phase II trial that evaluated efficacy of bevacizumab alone or in combination with irinotecan, using the Cox regression models adjusted for age, baseline Karnofsky performance score, first vs second relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between responders and nonresponders were calculated. Additional analyses were performed to test robustness, validity, fit, and accuracy of the models. The relationships between progression-free survival (PFS) and survival and between OR and PFS were also explored. There were 55 responders and 112 nonresponders across the 2 treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically significant predictor of survival (HR ≤ 0.52, P < .01). PFS was also a statistically significant predictor of survival at each landmark (HR ≤ 0.25, P < .0001). The association between OR and PFS was not statistically significant, likely due to inadequate statistical power for the analysis. Clarifying the relationship of OR and survival is important for determining whether OR can be a reliable predictor of the benefit of a therapeutic agent in patients with recurrent GBM.
authors.affiliation: Department of Neurosurgery, University of California-San Francisco, 400 Parnassus Ave., A-808, San Francisco, CA 94143, USA. pradosm@neurosurg.ucsf.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.forename: Meghna
authors.initials: M
authors.lastname: Samant
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Nina
authors.initials: N
authors.lastname: Paleologos
authors.forename: Martin K
authors.initials: MK
authors.lastname: Nicholas
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
authors.forename: James
authors.initials: J
authors.lastname: Vredenburgh
authors.forename: Asha
authors.initials: A
authors.lastname: Das
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab