title: Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study.
abstract: OBJECTIVE
  Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma.
  
  
  METHODS
  Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle.
  
  
  RESULTS
  The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance.
  
  
  CONCLUSIONS
  Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.
authors: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jdegroot@mdanderson.org
authors: John F
authors: JF
authors: de Groot
authors: Kathleen R
authors: KR
authors: Lamborn
authors: Susan M
authors: SM
authors: Chang
authors: Mark R
authors: MR
authors: Gilbert
authors: Timothy F
authors: TF
authors: Cloughesy
authors: Kenneth
authors: K
authors: Aldape
authors: Jun
authors: J
authors: Yao
authors: Edward F
authors: EF
authors: Jackson
authors: Frank
authors: F
authors: Lieberman
authors: H Ian
authors: HI
authors: Robins
authors: Minesh P
authors: MP
authors: Mehta
authors: Andrew B
authors: AB
authors: Lassman
authors: Lisa M
authors: LM
authors: Deangelis
authors: W K Alfred
authors: WK
authors: Yung
authors: Alice
authors: A
authors: Chen
authors: Michael D
authors: MD
authors: Prados
authors: Patrick Y
authors: PY
authors: Wen
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