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NRG/RTOG 1122: A phase 2, double-blinded, placebo-controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma.

Authors :
Lee, Eudocia Q.
Zhang, Peixin
Wen, Patrick Y.
Gerstner, Elizabeth R.
Reardon, David A.
Aldape, Kenneth D.
deGroot, John F.
Pan, Edward
Raizer, Jeffrey J.
Kim, Lyndon J.
Chmura, Steven J.
Robins, H. Ian
Connelly, Jennifer M.
Battiste, James D.
Villano, John L.
Wagle, Naveed
Merrell, Ryan T.
Wendland, Merideth M.
Mehta, Minesh P.
Source :
Cancer (0008543X); Jun2020, Vol. 126 Issue 12, p2821-2828, 8p
Publication Year :
2020

Abstract

<bold>Background: </bold>Targeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)-TIE2 system may play a role in tumor survival under VEGF inhibition. We conducted a phase 2, double-blinded, placebo-controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM.<bold>Methods: </bold>Patients ≥18 years of age with a Karnofsky performance status ≥70 and GBM or variants in first or second relapse were randomized to bevacizumab 10 mg/kg every 2 weeks plus trebananib 15 mg/kg every week or bevacizumab plus placebo. The primary endpoint was 6-month progression-free survival (PFS).<bold>Results: </bold>After an initial 6-patient lead-in cohort confirmed the safety of combining bevacizumab and trebananib, 115 eligible patients were randomized to the control (n = 58) or experimental treatment (n = 57). In the control arm, 6-month PFS was 41.1%, median survival time was 11.5 months (95% CI, 8.4-14.2 months), median PFS was 4.8 months (95% CI, 3.8-7.1 months), and radiographic response (RR) was 5.9%. In the experimental arm, 6-month PFS was 22.6%, median survival time was 7.5 months (95% CI, 6.8-10.1 months), median PFS was 4.2 months (95% CI, 3.7-5.6 months), and RR was 4.2%. The rate of severe toxicities was not significantly different between arms.<bold>Conclusion: </bold>The combination of bevacizumab and trebananib was well tolerated but did not significantly improve 6-month PFS rate, PFS, or OS for patients with rGBM over bevacizumab alone. The shorter PFS in the experimental arm with a hazard ratio of 1.51 (P = .04) suggests that the addition of trebananib to bevacizumab is detrimental. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0008543X
Volume :
126
Issue :
12
Database :
Complementary Index
Journal :
Cancer (0008543X)
Publication Type :
Academic Journal
Accession number :
143380964
Full Text :
https://doi.org/10.1002/cncr.32811