@article{d0500242ad364925aa125d0030b9278d,
title = "NRG/RTOG 1122: A phase 2, double-blinded, placebo-controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma",
abstract = "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.",
keywords = "angiogenesis, angiopoietin, bevacizumab, glioblastoma, trebananib",
author = "Lee, {Eudocia Q.} and Peixin Zhang and Wen, {Patrick Y.} and Gerstner, {Elizabeth R.} and Reardon, {David A.} and Aldape, {Kenneth D.} and deGroot, {John F.} and Edward Pan and Raizer, {Jeffrey J.} and Kim, {Lyndon J.} and Chmura, {Steven J.} and Robins, {H. Ian} and Connelly, {Jennifer M.} and Battiste, {James D.} and Villano, {John L.} and Naveed Wagle and Merrell, {Ryan T.} and Wendland, {Merideth M.} and Mehta, {Minesh P.}",
note = "Funding Information: This study was supported by the National Cancer Institute (grants U10CA180868, U10CA180822, and UG1CA189867) and Amgen. Funding Information: Eudocia Q. Lee has been a consultant for Eli Lilly and has received royalties from Up to Date, Inc. Peixin Zhang is an employee of Jazz Pharmaceuticals. Patrick Y. Wen has received grant/research/clinical trial support from Lilly USA, Agios, AstraZeneca, Beigene, Eli Lily, ImmunocellularTherapeutics, Kazia, Kadmon, Karyopharm, Merck, Novartis, Oncoceutics, Sanofi‐Aventis, Vascular Biogenics, and VBI Vaccines; is on the speaker's bureau for Merck; has received speaker fees from Prime Oncology; has been a consultant for Roche, Taiho Oncology, Novartis, and Agios Pharmaceuticals; and has served on the advisory board for Merck, Puma, Abbvie, Astra Zeneca, Bayer, Blue Earth Diagnostics, Eli Lilly, Deciphera, Genentech/Roche, GW Pharmaceuticals, Immunomic Therapeutics, Kadmon, Kiyatec, Vascular Biogenics, VBI Vaccines, Ziopharm, Taiho Oncology, DSMB Monteris, and Tocagen. David A. Reardon has received grants from Agenus, Celldex, EMD Serono, Inovio, Acerta Pharmaceuticals, Incyte, Inocia, Midatech, Omniox, and Tragara and has received personal fees from Agenus, Celldex, EMD Serono, Inovio, Abbvie, Advantagene, Amgen, Bayer, Bristol‐Myers Squibb, DelMar, Genentech/Roche, Merck, Merck KGaA, Monteris, Novocure, Oncorus, Oxigene, Regeneron, Stemline, and Taiho Oncology. Jeffrey J. Raizer owns stock in Celldex and Agenus, owns stock options in Astra‐Zeneca, and is employed by Astellas. Minesh P. Mehta has received grants from Novocure; has received personal fees from Karyopharm, Insys, Remedy, IBA, Varian, Celgene, Abbvie, AstraZeneca, Tocagen, and Blue Earth Diagnostics; and is on the Board of Directors for Oncoceutics. The other authors made no disclosures. Publisher Copyright: {\textcopyright} 2020 American Cancer Society",
year = "2020",
month = jun,
day = "15",
doi = "10.1002/cncr.32811",
language = "English (US)",
volume = "126",
pages = "2821--2828",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "12",
}