A national clinical trial led by the Oncology Clinical Trials Alliance found that the CDK 4/6 inhibitor abemaciclib may slow tumor growth in patients with advanced meningioma who carry certain genetic mutations. The primary analysis of Alliance A071401 was Dr. Priscilla Vlastinosand colleagues natural medicine.

Dr. Priscilla Vlastinos

Meningiomas (tumors that grow in the membranes surrounding the brain and spinal cord) are the most common primary brain tumor. Most are benign or treatable, but some meningiomas are aggressive and have mutations in genes such as: NF2 Alterations in the CDK pathway can be fatal. For patients whose meningioma is thought to be cancerous and continues to recur or grow after surgery or radiation therapy, options are very limited.

“Patients with recurrent or progressive high-grade meningiomas have historically had few treatment options, and most previous drug therapy trials have been disappointing,” said Dr. Vlastinos, a neuro-oncologist at Massachusetts General Brigham Cancer Institute and co-chair of the Alliance Neuro-Oncology Committee.

Noting that this trial is the first national study to enroll patients based on mutation testing, Dr. Vlastinos said the study “demonstrates that genome-driven testing for meningioma patients is feasible and that targeted therapies have the potential to improve outcomes for patients with specific genetic mutations.”

of Alliance A071401 The study followed patients with grade 2 or 3 meningioma whose tumors became infected. NF2 Mutations or changes in the CDK pathway. All patients evaluated had previously undergone surgery, radiotherapy, or both. Patients received an average of nine cycles of abemaciclib, a drug currently approved by the U.S. Food and Drug Administration for certain breast cancers.

Of the first 24 patients treated with abemaciclib, 58% had high-grade tumors that did not progress within 6 months of starting treatment. There was no control group in this study because there were no standard treatment options available for patients with high-grade tumors after surgery or radiation therapy. However, these results compare favorably with previous studies in which an average of 0% to 29% of patients with grade 2 or 3 meningioma had cancer that did not progress within 6 months of starting experimental treatment.

In the Alliance A071401 trial, median progression-free survival was 10 months and median overall survival was 29 months. Side effects were similar to those experienced by patients taking CDK inhibitors for other cancers, including diarrhea, fatigue, headache, and nausea/vomiting. Approximately one-quarter of patients experienced grade 3 or grade 4 adverse events that were considered possibly or likely related to treatment.

“While we are encouraged by these exciting results, we still have much work to do to improve treatments for this understudied patient population,” Dr. Brastianos said.

Disclosure: This study was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. This study was led and conducted by the Center for Clinical Trials in Oncology as part of a collaboration with AstraZeneca, Eli Lilly and Company, GSK, Damon Runyon Cancer Research Foundation, and Alexandra Drane, with participation from the NCI-funded National Clinical Trials Network.