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01-03-2016 | Clinical Study

A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas

Authors: Yazmin Odia, Fabio M. Iwamoto, Argirios Moustakas, Tyler J. Fraum, Carlos A. Salgado, Aiguo Li, Teri N. Kreisl, Joohee Sul, John A. Butman, Howard A. Fine

Published in: Journal of Neuro-Oncology | Issue 1/2016

Abstract

We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10 mg/kg intravenously biweekly. Clinical evaluations were repeated every 4 weeks. Magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4 months, respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 (22 %) had partial or complete response and 20/37 (54 %) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7–9/24 (29.2–37.5 %). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.

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Title: A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas
Authors: Yazmin Odia
Fabio M. Iwamoto
Argirios Moustakas
Tyler J. Fraum
Carlos A. Salgado
Aiguo Li
Teri N. Kreisl
Joohee Sul
John A. Butman
Howard A. Fine
Publication date: 01-03-2016
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-015-2020-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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