Multicenter phase 2 trial of abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations

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. One arm of the Alliance umbrella trial A071401 evaluated the CDK4/6 inhibitor abemaciclib in patients with grade 2 or 3 meningiomas and NF2 mutations or CDK pathway alterations. Among 36 patients treated, the median follow-up was 21 months. Among the first 24 patients, the best response was stable disease in 16 patients. Progression-free survival at 6 months (PFS6) was seen in 14 patients (58%; 95% CI 37-78), meeting the primary PFS6 endpoint. Of the 36 patients who started treatment, nine had a grade 3 and two had grade 4 events at least possibly related to treatment. The authors conclude that abemaciclib was well tolerated and resulted in improved PFS6.