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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
Author(s) -
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.
Publication year - 2020
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32811
Subject(s) - medicine , bevacizumab , clinical endpoint , placebo , progression free survival , phases of clinical research , gliosarcoma , surgery , adverse effect , randomized controlled trial , oncology , glioblastoma , clinical trial , overall survival , chemotherapy , pathology , cancer research , alternative medicine
Background 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. Methods 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). Results 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. Conclusion 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.