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

• Published in: Cancer 2018-04, Vol.124 (7), p.1438-1448
• Main Authors: Reardon, David A., Lassman, Andrew B., Schiff, David, Yunus, Shakeeb A., Gerstner, Elizabeth R., Cloughesy, Timothy F., Lee, Eudocia Quant, Gaffey, Sarah C., Barrs, Jennifer, Bruno, Jennifer, Muzikansky, Alona, Duda, Daniel G., Jain, Rakesh K., Wen, Patrick Y.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis; Angiopoietin; Angiopoietins - antagonists & inhibitors; Angiopoietins - metabolism; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - administration & dosage; Biomarkers; Biomarkers, Tumor - metabolism; Brain cancer; Cancer; Cohort Studies; Confidence intervals; Female; Follow-Up Studies; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Immunotherapy; Interleukins; Male; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Oncology; Patients; phase 2; Prognosis; Recombinant Fusion Proteins - administration & dosage; Survival; Survival Rate; Targeted cancer therapy; Toxicity; Vascular endothelial growth factor; vascular endothelial growth factor (VEGF)
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31172

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. Glioblastoma is a highly angiogenic cancer, yet therapeutics that block vascular endothelial growth factor have not improved survival, implicating potential compensatory pathways associated with angiogenesis. In this phase 2 study, angiopoietin inhibition using trebananib with or without bevacizumab is ineffective as treatment for patients with recurrent glioblastoma.