Abemaciclib Improves PFS in Tough-to-Treat Meningiomas

Findings from the phase 2 Alliance A071401 trial (NCT02523014) showed that the CDK4/6 inhibitor abemaciclib (Verzenio) yielded improvements in progression-free survival at 6 months (PFS6) in patients with recurrent or progressive grade 2 or 3 meningiomas harboring a somatic NF2 or CDK pathway alteration.

Data published in Nature Medicine showed that the PFS6 was 58% (95% CI, 36.6%-77.9%; 90% CI, 39.7%-75.4%) in the primary analysis cohort (n = 14/24), significantly exceeding the prespecified success threshold and meeting the primary end point. While no objective tumor responses were observed, the best response was stable disease in 67% (95% CI, 44.7%-84.4%) of patients, a clinically meaningful outcome for tumors that were previously progressing.

The median PFS was 10.1 months (95% CI, 3.6-20.2) for the first 24 evaluable patients and 7.6 months (95% CI, 3.6-17.1) for all 35 evaluable patients. In the 23 patients who achieved stable disease, the median PFS was 11.1 months (95% CI, 8.1-20.6). The median overall survival was 29.1 months (95% CI, 26.3-not evaluable) in both the primary analysis cohort of 24 patients and full evaluable cohort of 35 patients.

Exploratory analysis revealed that patients with NF2 alterations alone experienced a significantly longer PFS of 12.1 months compared with those with CDK pathway alterations. The treatment was well tolerated, with a safety profile consistent with prior studies of abemaciclib. The trial validates the feasibility of genomically driven studies for meningioma and establishes abemaciclib as a therapy warranting further investigation.

In an interview with Targeted Oncology, senior author Priscilla Brastianos, MD, neuro-oncologist with the Mass General Brigham Cancer Institute and co-chair of the Alliance Neuro-Oncology Committee, discussed the findings and their implications for this patient population, for whom effective systemic treatments are severely limited.

Targeted Oncology: What are the unmet needs in this patient population that inspired this research?

Priscilla Brastianos, MD: Patients with meningiomas that recur or progress after surgery and radiation have very limited systemic treatment options, and there is no established standard therapy in that setting. This is particularly true for higher-grade disease, where recurrence rates are higher and outcomes are poorer, making the need for effective, biology-driven therapies urgent.

How does the design of this study vary from previous studies in this disease state?

This study differs from prior meningioma trials in that it was a genomically driven, national cooperative group phase 2 study that enrolled patients based on defined tumor alterations, specifically NF2 or CDK pathway changes, rather than treating an unselected meningioma population. It also used prespecified co-primary end points, [PFS6] and response rate, to rigorously evaluate clinical activity in a disease where durable disease control is often more informative than tumor shrinkage.

Were any of the findings particularly surprising?

What was most encouraging was that we observed clear clinical activity in a molecularly defined subset of meningiomas, a disease where systemic therapies have historically shown very limited benefit. In particular, patients with NF2-altered tumors experienced meaningful disease control and favorable [PFS], reinforcing the importance of molecular selection in this disease.

What do you see as the next step in this line of research?

The next step is to build on this signal by refining which molecular subsets benefit most from CDK4/6 inhibition and identifying predictive biomarkers of response. In parallel, we need to explore rational combination strategies and test these approaches prospectively.

What would be your key takeaways for practicing oncologists based on these findings?

First, genomically selected trials in meningioma are feasible and can identify meaningful clinical activity in a space where systemic options are scarce. Second, in progressive grade 2/3 meningiomas with NF2 or CDK pathway alterations, abemaciclib was well tolerated and was associated with encouraging progression-free outcomes driven largely by durable disease control, supporting continued investigation of CDK4/6 inhibition in this population.

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. 2026 Jan 16. doi: 10.1038/s41591-025-04141-4. Epub ahead of print. PMID: 41545592.