Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial

作者：Priscilla K. Brastianos, Katharine Dooley, Susan Geyer, Elizabeth R. Gerstner, Timothy J. Kaufmann, A. John Iafrate, Maria Martinez-Lage, Mohammed Milhem, Mary Welch, Thomas Kaley, Jan Drappatz, Amy Chan, Priya Kumthekar, Carlos Kamiya Matsuoka, Roy E. Strowd, Adam L. Cohen, Kurt Jaeckle, Lindsay Robell, Rajiv S. Magge, Joo Yeon Nam, Nicholas Blondin, Nawal Shaikh, Ian Rabinowitz, Alissa A. Thomas, David Piccioni, Paul Brown, Stefan T. Kaluziak, Elizabeth Codd, Daniel P. Cahill, Sandro Santagata, Frederick G. Barker, Evanthia Galanis · 发表于：Nature Medicine · 年份：2026 · DOI：10.1038/s41591-025-04141-4 · 被引用次数：1 · 研究领域：Meningioma and schwannoma management、Neurofibromatosis and Schwannoma Cases、Brain Metastases and Treatment

Systemic treatments are limited for patients with meningiomas that have progressed after surgery or radiation. Loss of NF2 and CDKN2A/CDKN2B 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 NF2 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 = 37-78%), 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 incl...