Dr. Brastianos on Recent Data in High-Grade Meningiomas

Priscilla K. Brastianos, MD, an associate professor of medicine with Harvard Medical School and a physician-scientist at Massachusetts General Hospital Cancer Center, investigates the genomic drivers of brain tumors. She says there is a clear unmet need for systemic treatment options for aggressive, high-grade meningiomas.

Approximately 80% of meningiomas are grade 1 or benign. Many of those are small, asymptomatic, and indolent, and may not require immediate treatment. Surveillance is a viable treatment option for many patients. Those with grade I tumors who do require treatment can often be treated effectively with surgery with or without radiation.

However, the remaining 20% are the more aggressive grade II and grade III tumors. Grade III meningiomas are malignant tumors that infiltrate the brain and are at high risk for recurrence.

Many investigators have produced findings deepening the field’s understanding of the genomics of meningioma. Investigators in Brastianos’ laboratory identified recurrent SMO and ATK1 mutations as oncogenic drivers in the disease. Those findings led to the multicenter, National Cancer Institute Cooperative Group phase 2 Alliance A071401 trial (NCT02523014).

Investigators in the multi-arm study are assessing the efficacy and safety of vismodegib (Erivedge), the focal adhesion kinase (FAK) inhibitor GSK2256098, the investigational AKT inhibitor capivasertib, or abemaciclib (Verzenio) in patients with progressive meningioma.

In January 2023, Brastianos published grade II results from 36 patients with NF2 mutations assigned to GSK2256098. The FAK inhibitor induced a 6-month progression-free survival (PFS) rate of 33% (95% CI, 16%-55%).

The PD-1 inhibitor pembrolizumab (Keytruda) has also produced intriguing results in patients with recurrent/residual high-grade meningiomas. In results from a single-arm, open-label phase 2 analysis (NCT03279692) of 25 evaluable patients published in March 2022, Brastianos and her collaborators observed a 6-month PFS rate of 48% (90% exact CI, 31%-66%) and a median PFS of 7.6 months (90% CI, 3.4-12.9).

Furthermore, those responses were durable, and investigators deemed pembrolizumab to have a tolerable safety profile.