{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:24:40Z","timestamp":1793316280892,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ\/RT\u2192TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood\u2013brain barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>European Organisation for Research and Treatment of Cancer 1709\/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age\u2005&amp;gt;\u200518 years and Karnofsky performance status\u2005&amp;gt;\u200570. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ\/RT\u2192TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR\u2005=\u20051.04; P\u2005=\u2005.64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR\u2005=\u20050.97; P\u2005=\u2005.67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR\u2005=\u20051.13; P\u2005=\u2005.27). More CTCAE grade 3\/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noae053","type":"journal-article","created":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T19:07:13Z","timestamp":1710702433000},"page":"1670-1682","source":"Crossref","is-referenced-by-count":56,"title":["Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-214X","authenticated-orcid":false,"given":"Patrick","family":"Roth","sequence":"first","affiliation":[{"name":"Department of Neurology and Brain Tumor Center, University Hospital Zurich , Zurich , Switzerland"},{"name":"Department of Neurology,\u00a0University of Zurich , Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Gorlia","sequence":"additional","affiliation":[{"name":"European Organisation for Research and Treatment of Cancer (EORTC) , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap C","family":"Reijneveld","sequence":"additional","affiliation":[{"name":"Department of Neurology & Brain Tumor Center, Amsterdam University Medical Centers , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"de Vos","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht, University Utrecht , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-1204","authenticated-orcid":false,"given":"Ahmed","family":"Idbaih","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, AP-HP, Institut du Cerveau \u2013 Paris Brain Institute \u2013 ICM, Inserm, CNRS, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re \u2013 Charles Foix, DMU Neurosciences, Service de Neurologie 2-Mazarin , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-S\u00e9bastien","family":"Frenel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut de Cancerologie de L\u2019Ouest , Saint-Herblain , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-3278","authenticated-orcid":false,"given":"Emilie","family":"Le Rhun","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de neurochirurgie , Lille , France"},{"name":"Univ. Lille, Inserm, CHU Lille, U1192, Laboratoire Prot\u00e9omique, R\u00e9ponse Inflammatoire et Spectrom\u00e9trie de Masse (PRISM) , Lille , France"},{"name":"Department of Neurosurgery & Clinical Neuroscience Center, University Hospital and University of Zurich , Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Sepulveda","sequence":"additional","affiliation":[{"name":"Neuro-Oncology Unit, Department of Medical Oncology, Instituto de Investigaci\u00f3n Hospital 12 de Octubre , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Perry","sequence":"additional","affiliation":[{"name":"Division of Neurology, Sunnybrook HSC, University of Toronto , Toronto, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G Laura","family":"Masucci","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Centre Hospitalier de 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