@article{1fc6d1ef494147e1b7725f07a32bb3d7,
title = "A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: Results of NRG Oncology RTOG 0913",
abstract = "Background This phase II study was designed to determine the efficacy of the mammalian target of rapamycin (mTOR) inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Methods Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities. Results A total of 171 patients were randomized and deemed eligible for this study. Patients randomized to receive everolimus experienced a significant increase in both grade 4 toxicities, including lymphopenia and thrombocytopenia, and treatment-related deaths. There was no significant difference in PFS between patients randomized to everolimus compared with control (median PFS time: 8.2 vs 10.2 mo, respectively; P = 0.79). OS for patients randomized to receive everolimus was inferior to that for control patients (median survival time: 16.5 vs 21.2 mo, respectively; P = 0.008). A similar trend was observed in both O 6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated tumors. Conclusion Combining everolimus with conventional chemoradiation leads to increased treatment-related toxicities and does not improve PFS in patients with newly diagnosed glioblastoma. Although the median survival time in patients receiving everolimus was comparable to contemporary studies, it was inferior to the control in this randomized study.",
keywords = "everolimus, glioblastoma, mTOR inhibition, phase II trial, radiation sensitizer",
author = "Prakash Chinnaiyan and Minhee Won and Wen, {Patrick Y.} and Rojiani, {Amyn M.} and Maria Werner-Wasik and Shih, {Helen A.} and Ashby, {Lynn S.} and {Michael Yu}, {Hsiang Hsuan} and Stieber, {Volker W.} and Malone, {Shawn C.} and Fiveash, {John B.} and Mohile, {Nimish A.} and Ahluwalia, {Manmeet S.} and Wendland, {Merideth M.} and Stella, {Philip J.} and Kee, {Andrew Y.} and Mehta, {Minesh P.}",
note = "Funding Information: William Beaumont Hospital, Royal Oak, Michigan, USA (P.C.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA (M.W.); Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA (P.Y.W.); Augusta University–Medical College of Georgia, Augusta, Georgia, USA (A.M.R.); Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA (M.W.W.); Massachusetts General Hospital, Boston, Massachusetts, USA (H.A.S.); Barrow Neurological Institute accruals under Arizona Oncology Services Foundation, Phoenix, Arizona, USA (L.S.A.); H. Lee Moffitt Cancer, Tampa, Florida, USA (H-H.M.Y.); Novant Health Forsyth Regional Cancer Center accruals under Southeast Cancer Control Consortium, Inc, CCOP, Goldsboro, North Carolina, USA (V.W.S.); The Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario, Canada (S.C.M.); University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA (J.B.F.); University of Rochester, Rochester, New York, USA (N.A.M.); Cleveland Clinic Foundation, Cleveland, Ohio, USA (M.S.A.); Willamette Valley Cancer Institute, Eugene, Oregon, USA (M.M.W.); Saint Joseph Mercy Hospital accruals under Michigan Cancer Research Consortium CCOP, Ypsilanti, Michigan, USA (P.J.S.); Legacy Health Systems accruals under Mayo Clinic, Portland, Oregon, USA (A.Y.K.); Baptist Hospital of Miami, Miami, Florida, USA (M.P.M.) Funding Information: This work was supported by the National Cancer Institute, NRG Oncology Operations (U10CA180868), NRG Oncology SDMC (U10CA180822), and Novartis. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2018",
month = apr,
day = "9",
doi = "10.1093/neuonc/nox209",
language = "English (US)",
volume = "20",
pages = "666--673",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "5",
}
