Phase 2 and biomarker study of trebananib, an angiopoietin-blocking peptibody, with and without bevacizumab for patients with recurrent glioblastoma

Cancer. 2018 Apr 1;124(7):1438-1448. doi: 10.1002/cncr.31172. Epub 2017 Dec 19.

Abstract

Background: Angiopoietins contribute to tumor angiogenesis and may be upregulated as a compensatory factor after vascular endothelial growth factor (VEGF) blockade. The authors performed a phase 2 and biomarker study to evaluate trebananib, an angiopoietin 1 and angiopoietin 2 blocking peptibody, with and without bevacizumab in patients with recurrent glioblastoma.

Methods: Forty-eight patients who had bevacizumab-naive, recurrent glioblastoma were treated with trebananib (30 mg/kg weekly) as single agent (n = 11) or combined with bevacizumab (n = 37). The primary endpoint was 6-month progression-free survival rate as determined by investigator review. Circulating biomarker levels were assessed before and after study therapy.

Results: Trebananib was well tolerated as monotherapy and did not enhance bevacizumab-associated toxicity. Trebananib had no single-agent activity, and all treated patients exhibited progressive disease within 2 months. The 6-month progression-free survival rate for trebananib plus bevacizumab was 24.3% (95% confidence interval [CI], 12.1%-38.8%); whereas the median overall survival was 9.5 months (95% CI, 7.5-4.7 months), and the 12-month overall survival rate was 37.8% (95% CI, 22.6%-53.0%). Baseline and post-treatment changes in circulating vascular VEGF and interleukin-8 levels were correlated with survival among patients who received trebananib plus bevacizumab.

Conclusions: Angiopoietin 1 and angiopoietin 2 inhibition with trebananib was ineffective as monotherapy and did not enhance the ability of VEGF blockade with bevacizumab to improve the outcomes of patients with recurrent glioblastoma. Cancer 2018;124:1438-48. © 2017 American Cancer Society.

Keywords: angiogenesis; angiopoietin; glioblastoma; phase 2; vascular endothelial growth factor (VEGF).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiopoietins / antagonists & inhibitors*
  • Angiopoietins / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Recombinant Fusion Proteins / administration & dosage
  • Survival Rate

Substances

  • Angiopoietins
  • Biomarkers, Tumor
  • Recombinant Fusion Proteins
  • Bevacizumab
  • trebananib