Abemaciclib Shows Encouraging Activity in Recurrent/Progressive Meningioma

Abemaciclib (Verzenio) demonstrated clinical activity in patients with recurrent or progressive meningiomas harboring somatic NF2 or CDK pathway alterations, according to data from the phase 2 Alliance A071401 trial (NCT02523014) published in Nature Medicine. The study represents a milestone as the first national investigation of precision medicine in genetically defined subclasses of meningioma, a disease with historically limited systemic treatment options once surgery and radiation have failed.

Clinical Efficacy

The trial met its primary end point of progression-free survival (PFS) at 6 months. Among the first 24 evaluable patients, the observed PFS rate at 6 months was 58.3% (95% CI, 36.6%-77.9%), which significantly exceeded the prespecified success threshold of 8 patients. No complete or partial responses were observed; however, the best response was stable disease in 16 of 24 patients (67%; 95% CI, 44.7%-84.4%).

The median overall survival (OS) reached 29.1 months (95% CI, 26.3-not evaluable) in the primary evaluation cohort. Among the first 24 evaluable patients, the median PFS was 10.1 months (95% CI, 3.6-20.2). Exploratory analyses revealed that patients with NF2 alterations alone experienced a significantly longer median PFS of 12.1 months (95% CI, 7.6-20.6) compared with 2.4 months (95% CI, 1.6-not evaluable) in those with CDK pathway alterations alone and 2.0 months (95% CI, 1.5-not evaluable) in those with both alterations (P = .0094). Additionally, higher levels of p16 expression by immunohistochemistry were associated with clinical benefit with abemaciclib.

Expert Commentary

“In conclusion, we demonstrate that genomically driven trials for patients with meningiomas are feasible,” wrote lead study author Priscilla K. Brastianos, MD, of Massachusetts General Hospital Cancer Center, and coauthors in the paper. “Abemaciclib was well tolerated and showed encouraging activity in patients with recurrent or progressive high-grade meningioma with CDK pathway or NF2 alterations.”

Trial Breakdown

The Alliance A071401 trial was a genomically driven umbrella study evaluating targeted therapies in patients with recurrent or progressive meningiomas. The abemaciclib arm specifically enrolled patients with World Health Organization (WHO) grade 2 or 3 tumors. The treatment regimen consisted of abemaciclib administered as an oral continuous dose at 200 mg twice daily. Patients received a mean of 9 treatment cycles, with 33% requiring a treatment delay in at least 1 cycle.

Eligibility criteria required patients to have intracranial grade 2 or 3 meningioma, measurable disease, and documented somatic NF2 mutations or alterations in the CDK pathway. Patients must have had progressive or residual disease, defined as residual measurable disease immediately following surgery for grade 2 or 3 tumors, or an increase in lesion size by 25% or more over 25 months. Most enrolled patients had an ECOG performance status of 0 or 1 (88%) and had previously undergone at least 2 prior treatment modalities (96%), including surgery and radiation.

Safety Results

The safety analysis included 36 patients who received at least 1 dose of abemaciclib. Overall, the toxicity profile was consistent with the known safety patterns of CDK4/6 inhibitors. Treatment-related adverse events (TRAEs) of grade 3 occurred in 9 patients, while grade 4 TRAEs were reported in 2 patients. The specific grade 4 toxicities included aspartate aminotransferase elevation/alanine aminotransferase elevation and vomiting. Additionally, seven patients discontinued treatment due to AEs or complications. Other notable grade 3 TRAEs included anemia, decreased neutrophil count, and diarrhea. A treatment delay in at least 1 cycle was noted in 12 patients (33%).

Reference

Brastianos PK, Dooley K, Geyer S, et al. Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial. Nat Med. Published online January 16, 2026. doi:10.1038/s41591-025-04141-4