{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:07:28Z","timestamp":1767704848496,"version":"3.41.2"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Novel treatments are needed for oligodendroglioma that has recurred following radiotherapy (RT) and chemotherapy. The cyclin D1\u2013CDK4 axis is frequently dysregulated in oligodendroglioma. Abemaciclib is a selective CDK4\/6 inhibitor that achieves pharmacologically relevant concentrations in brain tumor tissue.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a single-arm, phase 2 trial evaluating the efficacy of abemaciclib in patients with recurrent oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant and 1p\/19q-codeleted, WHO grade 3, following prior RT and \u22651 line of alkylating chemotherapy. Patients received abemaciclib 200\u00a0mg twice daily. The primary endpoint was progression-free survival at 6 months (PFS-6).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ten patients were enrolled. The most common treatment-related adverse event was grade 1\u20132 diarrhea, occurring in all patients. Five patients (50%) were alive and progression-free at 6 months, below the minimum required (80%) to meet the primary endpoint. In patients with enhancing tumor (n\u2005=\u20059), best response was partial response in 2 patients (objective radiographic response = 22.2%; duration of response [DOR] 13.1 and 7.7 months), stable disease (SD) in 3 patients (33.3%; duration of SD 17.0, 6.7, and 2.5 months), progressive disease in 3 patients (33.3%), and nonevaluable in 1 patient (11.1%). The patient with nonenhancing tumor showed SD lasting 10.2 months. Median PFS was 7.7 months (95% CI, 1.7\u201313.1 months); median overall survival was not reached (median follow-up 17 months).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The efficacy of abemaciclib in recurrent grade 3 oligodendroglioma was inadequate to warrant further evaluation as monotherapy in unselected patients. However, given the objective responses and durable disease control observed in a subset of patients, further studies are warranted to identify subgroups that may benefit.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdaf011","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T12:29:27Z","timestamp":1737116967000},"source":"Crossref","is-referenced-by-count":1,"title":["A single-arm phase 2 study of abemaciclib in adult patients with recurrent grade 3 oligodendroglioma"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-3071","authenticated-orcid":false,"given":"Carson A","family":"Wills","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suyash","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-4552","authenticated-orcid":false,"given":"Ali","family":"Nabavizadeh","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thara","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Prior","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maikel","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"McCoy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivani","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Angeloni","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Frangos","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Blessing","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah","family":"Coghlan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Maloney","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-1128","authenticated-orcid":false,"given":"E Paul","family":"Wileyto","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arati S","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]},{"name":"Abramson Cancer Center, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-0539","authenticated-orcid":false,"given":"Stephen J","family":"Bagley","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]},{"name":"Abramson Cancer Center, University of Pennsylvania , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"issue":"8","key":"2025021210172418900_CIT0001","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol"},{"issue":"1","key":"2025021210172418900_CIT0002","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/cas.13878","article-title":"Amino acid metabolism-related gene expression-based risk signature can better predict overall survival for glioma","volume":"110","author":"Liu","year":"2019","journal-title":"Cancer Sci."},{"issue":"1","key":"2025021210172418900_CIT0003","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-024-00516-y","article-title":"Glioma","volume":"10","author":"Weller","year":"2024","journal-title":"Nat Rev Dis Primers."},{"issue":"2","key":"2025021210172418900_CIT0004","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10014-024-00480-1","article-title":"Oligodendroglioma, IDH-mutant and 1p\/19q-codeleted-prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy","volume":"41","author":"Sasaki","year":"2024","journal-title":"Brain Tumor Pathol."},{"issue":"7","key":"2025021210172418900_CIT0005","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1056\/NEJMoa2304194","article-title":"Vorasidenib in IDH1- or IDH2-mutant low-grade glioma","volume":"389","author":"Mellinghoff","year":"2023","journal-title":"N Engl J Med."},{"issue":"2","key":"2025021210172418900_CIT0006","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/neup.12789","article-title":"Recurrent oligodendroglioma with changed 1p\/19q status","volume":"42","author":"Barresi","year":"2022","journal-title":"Neuropathology"},{"issue":"7","key":"2025021210172418900_CIT0007","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12032-023-02071-0","article-title":"Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target","volume":"40","author":"Darabi","year":"2023","journal-title":"Med Oncol."},{"issue":"15","key":"2025021210172418900_CIT0008","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1158\/0008-5472.CAN-18-0342","article-title":"The tumor suppressor CIC directly regulates MAPK pathway genes via histone deacetylation","volume":"78","author":"Weissmann","year":"2018","journal-title":"Cancer Res."},{"issue":"6","key":"2025021210172418900_CIT0009","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00401-015-1424-1","article-title":"Oligodendroglioma: pathology, molecular mechanisms and markers","volume":"129","author":"Wesseling","year":"2015","journal-title":"Acta Neuropathol."},{"issue":"19","key":"2025021210172418900_CIT0010","doi-asserted-by":"crossref","first-page":"6174","DOI":"10.1158\/0008-5472.CAN-11-1031","article-title":"Cyclin D1 and cdk4 mediate development of neurologically destructive oligodendroglioma","volume":"71","author":"Ciznadija","year":"2011","journal-title":"Cancer Res."},{"issue":"3","key":"2025021210172418900_CIT0011","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/modpathol.2013.165","article-title":"Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors","volume":"27","author":"Chan","year":"2014","journal-title":"Mod Pathol."},{"issue":"6048","key":"2025021210172418900_CIT0012","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1126\/science.1210557","article-title":"Mutations in CIC and FUBP1 contribute to human oligodendroglioma","volume":"333","author":"Bettegowda","year":"2011","journal-title":"Science."},{"issue":"4","key":"2025021210172418900_CIT0013","first-page":"839","article-title":"Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis","volume":"7","author":"Ino","year":"2001","journal-title":"Clin Cancer Res."},{"issue":"8","key":"2025021210172418900_CIT0014","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/cam4.762","article-title":"Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors","volume":"5","author":"Kuo","year":"2016","journal-title":"Cancer Med"},{"issue":"12","key":"2025021210172418900_CIT0015","first-page":"1519","article-title":"CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas","volume":"21","author":"Appay","year":"2019","journal-title":"Neuro Oncol"},{"issue":"12","key":"2025021210172418900_CIT0016","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1007\/s40262-020-00930-x","article-title":"Clinical pharmacokinetics and pharmacodynamics of the cyclin-dependent kinase 4 and 6 inhibitors palbociclib, ribociclib, and abemaciclib","volume":"59","author":"Groenland","year":"2020","journal-title":"Clin Pharmacokinet."},{"issue":"20","key":"2025021210172418900_CIT0017","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1158\/1078-0432.CCR-20-1764","article-title":"A phase II study of abemaciclib in patients with brain metastases secondary to hormone receptor-positive breast cancer","volume":"26","author":"Tolaney","year":"2020","journal-title":"Clin Cancer Res."},{"issue":"14","key":"2025021210172418900_CIT0018","doi-asserted-by":"crossref","first-page":"OF1","DOI":"10.1158\/1078-0432.CCR-24-0562","article-title":"CDKN2A\/B homozygous deletion sensitizes IDH-mutant glioma to CDK4\/6 inhibition","volume":"30","author":"Nasser","year":"2024","journal-title":"Clin Cancer Res."},{"issue":"2","key":"2025021210172418900_CIT0019","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s13311-016-0507-6","article-title":"Modified criteria for radiographic response assessment in glioblastoma clinical trials","volume":"14","author":"Ellingson","year":"2017","journal-title":"Neurotherapeutics"},{"issue":"6","key":"2025021210172418900_CIT0020","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S1470-2045(11)70057-2","article-title":"Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas","volume":"12","author":"van den Bent","year":"2011","journal-title":"Lancet Oncol."},{"issue":"9","key":"2025021210172418900_CIT0021","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1200\/JCO.2001.19.9.2449","article-title":"Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy","volume":"19","author":"Chinot","year":"2001","journal-title":"J Clin Oncol."},{"issue":"5","key":"2025021210172418900_CIT0022","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1212\/01.WNL.0000137049.65631.DB","article-title":"Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas","volume":"63","author":"Triebels","year":"2004","journal-title":"Neurology."},{"issue":"20","key":"2025021210172418900_CIT0023","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.1002\/cncr.24524","article-title":"Temozolomide for recurrent intracranial supratentorial platinum-refractory ependymoma","volume":"115","author":"Chamberlain","year":"2009","journal-title":"Cancer."},{"issue":"1","key":"2025021210172418900_CIT0024","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ccell.2018.03.023","article-title":"CDK4\/6 inhibitors: the mechanism of action may not be as simple as once thought","volume":"34","author":"Klein","year":"2018","journal-title":"Cancer Cell"},{"issue":"5","key":"2025021210172418900_CIT0025","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s11523-020-00754-6","article-title":"Phase II trial of palbociclib in recurrent retinoblastoma-positive anaplastic oligodendroglioma: a study from the spanish group for research in neuro-oncology (GEINO)","volume":"15","author":"Sep\u00falveda-S\u00e1nchez","year":"2020","journal-title":"Target Oncol"},{"issue":"7804","key":"2025021210172418900_CIT0026","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41586-020-2209-9","article-title":"Mechanisms and therapeutic implications of hypermutation in gliomas","volume":"580","author":"Touat","year":"2020","journal-title":"Nature."},{"issue":"1","key":"2025021210172418900_CIT0027","doi-asserted-by":"crossref","first-page":"2094583","DOI":"10.1080\/2162402X.2022.2094583","article-title":"CDK4\/6 blockade provides an alternative approach for treatment of mismatch-repair deficient tumors","volume":"11","author":"Salewski","year":"2022","journal-title":"Oncoimmunology"},{"issue":"2","key":"2025021210172418900_CIT0028","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1148\/radiology.217.2.r00nv36377","article-title":"Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment","volume":"217","author":"Kumar","year":"2000","journal-title":"Radiology."}],"container-title":["Neuro-Oncology Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/noa\/advance-article-pdf\/doi\/10.1093\/noajnl\/vdaf011\/61484109\/vdaf011.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/7\/1\/vdaf011\/61484109\/vdaf011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/7\/1\/vdaf011\/61484109\/vdaf011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:18:02Z","timestamp":1739355482000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/noa\/article\/doi\/10.1093\/noajnl\/vdaf011\/7959396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/noajnl\/vdaf011","relation":{},"ISSN":["2632-2498"],"issn-type":[{"type":"electronic","value":"2632-2498"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2025,1]]},"article-number":"vdaf011"}}