David A Reardon1, Andrew B Lassman2, David Schiff3, Shakeeb A Yunus4, Elizabeth R Gerstner5, Timothy F Cloughesy6, Eudocia Quant Lee1, Sarah C Gaffey1, Jennifer Barrs1, Jennifer Bruno1, Alona Muzikansky7, Daniel G Duda8, Rakesh K Jain8, Patrick Y Wen1. 1. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 2. Department of Neurology, Columbia University Medical Center, New York, New York. 3. Department of Neurology, University of Virginia Medical Center, Charlottesville, Virginia. 4. Hematology/Oncology, University of Massachusetts Memorial Medical Center, Worchester, Massachusetts. 5. Department of Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts. 6. Department of Neurology, University of California, Los Angeles, Los Angeles, California. 7. Biostatistics, Massachusetts General Hospital, Boston, Massachusetts. 8. Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
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.
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.
Authors: Eudocia Q Lee; Peixin Zhang; Patrick Y Wen; Elizabeth R Gerstner; David A Reardon; Kenneth D Aldape; John F deGroot; Edward Pan; Jeffrey J Raizer; Lyndon J Kim; Steven J Chmura; H Ian Robins; Jennifer M Connelly; James D Battiste; John L Villano; Naveed Wagle; Ryan T Merrell; Merideth M Wendland; Minesh P Mehta Journal: Cancer Date: 2020-03-10 Impact factor: 6.860
Authors: Elizabeth A Kuczynski; Peter B Vermeulen; Francesco Pezzella; Robert S Kerbel; Andrew R Reynolds Journal: Nat Rev Clin Oncol Date: 2019-08 Impact factor: 66.675
Authors: Lakshmi Nayak; Annette M Molinaro; Katherine Peters; Jennifer L Clarke; Justin T Jordan; John de Groot; Leia Nghiemphu; Thomas Kaley; Howard Colman; Christine McCluskey; Sarah Gaffey; Timothy R Smith; David J Cote; Mariano Severgnini; Jennifer H Yearley; Qing Zhao; Wendy M Blumenschein; Dan G Duda; Alona Muzikansky; Rakesh K Jain; Patrick Y Wen; David A Reardon Journal: Clin Cancer Res Date: 2020-11-16 Impact factor: 12.531