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Loss of\n                    <jats:italic>NF2<\/jats:italic>\n                    and\n                    <jats:italic>CDKN2A\/<\/jats:italic>\n                    <jats:italic>CDKN2B<\/jats:italic>\n                    is common in higher-grade meningiomas and promotes progression in preclinical models. We evaluated the efficacy of abemaciclib, a cyclin-dependent kinase 4\/6 inhibitor, as one arm of the Alliance umbrella trial A071401, a genomically driven phase 2 study in recurrent and progressive meningiomas. Eligible patients with grade 2 or 3 tumors and\n                    <jats:italic>NF2<\/jats:italic>\n                    mutations or CDK pathway alterations were treated with abemaciclib. Two co-primary endpoints were used: progression-free survival at 6 months (PFS6) and response rate as defined by local review; the trial would be declared positive if either endpoint was met. The success threshold for PFS6 was 8 or more of 24 patients; for the response rate, it was 3 or more of 24 patients. Ninety-six patients were screened and 36 patients received treatment. The mean number of treatment cycles was nine and the median follow-up was 21 months. The first 24 patients who met the eligibility criteria and began treatment could be evaluated for the primary endpoint. The observed PFS6 rate was 58% (14 of 24 patients, 95% confidence interval\u2009=\u200937\u201378%), thus meeting the PFS6 criteria for promising activity. The best response was stable disease in 16 of 24 patients. Of the 36 patients who started treatment, nine had a grade 3 and two had grade 4 adverse events at least possibly related to treatment. Grade 4 toxicities included alanine aminotransferase elevation (1), aspartate aminotransferase elevation (1) and vomiting (1). The trial met its primary endpoint. Abemaciclib was well tolerated and resulted in improved PFS6. Abemaciclib warrants further investigation for patients with progressive grade 2 or 3 meningiomas harboring\n                    <jats:italic>NF2<\/jats:italic>\n                    or CDK pathway alterations. ClinicalTrials.gov registration no.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/study\/NCT02523014?term=brastianos&amp;rank=2\" ext-link-type=\"uri\">NCT02523014<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-04141-4","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:02:49Z","timestamp":1768557769000},"page":"717-724","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4470-8425","authenticated-orcid":false,"given":"Priscilla K.","family":"Brastianos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-5767","authenticated-orcid":false,"given":"Katharine","family":"Dooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5649-6909","authenticated-orcid":false,"given":"Susan","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Gerstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Iafrate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-7562","authenticated-orcid":false,"given":"Maria","family":"Martinez-Lage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Milhem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Roberta","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kaley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Drappatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-0677","authenticated-orcid":false,"given":"Priya","family":"Kumthekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-2728","authenticated-orcid":false,"given":"Carlos Kamiya","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy E.","family":"Strowd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-463X","authenticated-orcid":false,"given":"Kurt","family":"Jaeckle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Robell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv S.","family":"Magge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-0484","authenticated-orcid":false,"given":"Joo Yeon","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Blondin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-4865","authenticated-orcid":false,"given":"Ian","family":"Rabinowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa A.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Piccioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kaluziak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Codd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Cahill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Santagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Frederick G.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-786X","authenticated-orcid":false,"given":"Evanthia","family":"Galanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"4141_CR1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/neuonc\/not330","volume":"16","author":"T Kaley","year":"2014","unstructured":"Kaley, T. et al. 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A.L.C. has institutional grants and contracts from Chimerix, BPGbio, Nuvox, the University of Utah and Novocure. A.T. serves as site principal investigator for two industry-supported studies with Novocure and ONO Pharmaceuticals. D.P.C. has received financial compensation from Servier (2023), Boston Scientific (2025), Incephalo (2023), Pyramid Biosciences (equity options 2021), Lilly (2020), GlaxoSmithKline (2021) and Boston Pharmaceuticals (2020) for advisory input. He has also received financial compensation and travel reimbursement from Merck for invited lectures (2016), and from the US National Institutes of Health and Department of Defense for clinical trial and grant review (2025). E.G. serves on the advisory board for Kiyatec (personal compensation), Karyopharm Therapeutics, Boston Scientific, Servier Pharmaceuticals, Boehringer Ingelheim and Modifi Biosciences (compensation to employer), and has received grant, research and clinical trial funding (to Mayo) from Servier Pharmaceuticals and Denovo Biopharma. P.K. has received grants from Genentech and Novocure, consulted for Belay Diagnostics, FYR Diagnostics, Plus Therapeutics, Enclear Therapeutics, Affinia Therapeutics, Biocept, Janssen, Bioclinical, Mirati, Novocure, Servier, Telix Pharmaceuticals and Biodexa, received payments and honoraria from Seagen, and participated in data safety monitoring board or advisory board for BPGBio and In8Bio. P.K.B. has consulted for Voyager Therapeutics, Tesaro, SK Life Science, Sintetica, Pfizer, Merck, ElevateBio, Dantari, Angiochem, MPM, Medscape, Kazia, InCephalo, Genentech, Eli Lilly, CraniUS, Axiom, Atavistik and Advise Connect Inspire, serves on the scientific advisory board for Kazia, Selectin Therapeutics (with equity) and CraniUS, and has received speaker\u2019s honoraria from the International Academy for Advanced Oncology, Genentech and Pfizer. She has received institutional research support (to MGH) from Kinnate, Mirati, Merck and Eli Lilly. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}