Meningiomas are the most common type of brain cancer—the American Society of Clinical Oncology estimates that the disease represents approximately 40% of primary brain tumors and will affect 42,260 people in the United States in 2023. 

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 human brain tumors. She notes that the disease arises in the meninges, which are layers of membranes surrounding the spine and brain.

The World Health Organization (WHO) says approximately 80% of these tumors are benign, or grade I. Brastianos says that many low-grade tumors are indolent and can be fully resolved with resection. Some do not require immediate treatment. Tumors that are asymptomatic, small, and slow growing can be “treated” with observation alone.

However, the remaining 20% of tumors are grade II, which are more likely to recur following treatment, or grade III, which are both malignant and more likely to recur. Brastianos says that the WHO has identified molecular biomarkers, including 

 promoter mutations and CDKN2a status, that are associated with high rates of progression and poorer survival in patients with high-grade tumors. Recurrence in grade III meningiomas can be as high as 90%.

The WHO defines high-grade tumors as those that have “20 or more mitosis per 10 high-power field, malignant characteristics resembling carcinoma, sarcoma, or melanoma; or a high-risk molecular feature.”

Prognosis depends on a variety of factors including tumor size, location, and grade, she says. Survival is shorter in those with grade II/III tumors. CDKN2 loss and alterations in 

 promoter are also associated with poorer survival, Brastianos says.

Currently, there is no systemic therapy available for high-grade meningiomas. Brastianos said treatment consists of multidisciplinary teams including surgery and radiation. Patient factors such as age and comorbidities play a role in treatment decisions, she concludes.

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Priscilla K. Brastianos, MD, explains the differences between low-grade meningiomas and aggressive high-grade tumors.

Dr Brastianos Breaks Down the Basics of 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 

 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 

 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.

Priscilla K. Brastianos, MD, reviews recent findings in high-grade meningiomas, including data generated in her laboratory.

Priscilla K. Brastianos, MD

Articles

Dr Brastianos Breaks Down the Basics of Meningiomas

Dr. Brastianos on Recent Data in High-Grade Meningiomas