Targeted Therapy Abemaciclib Shows Activity in Aggressive Meningiomas

A national clinical trial led by the Alliance for Clinical Trials in Oncology has found that the CDK 4/6 inhibitor abemaciclib may slow tumor growth in patients with aggressive meningiomas that have specific genetic mutations. The primary analysis of Alliance A071401 was published by Priscilla Brastianos, MD, and colleagues in Nature Medicine. Priscilla Brastianos, MD Meningiomas—tumors that grow in the membranes that surround the brain and spinal cord—are the most common primary brain tumors. While most are benign or treatable, aggressive meningiomas with mutations in genes like NF2 and alterations in the CDK pathway can be fatal. Options are extremely limited for patients whose meningiomas are considered cancerous and return or continue to grow after surgery and radiation therapy. “Patients with recurrent or progressive high-grade meningiomas have historically had very few treatment options, and most prior trials of medical therapy have been disappointing,” said Dr. Brastianos, a neuro-oncologist with the Mass General Brigham Cancer Institute and co-chair of the Alliance Neuro-Oncology Committee. Noting that the trial was the first national study to enroll patients based on mutational testing, Dr. Brastianos said that the research “shows that genomically driven trials for patients with meningioma are feasible and that targeted therapy may improve outcomes for patients with specific genetic mutations.” The Alliance A071401 trial followed patients with grade 2 or 3 meningiomas whose tumors carried NF2 mutations or CDK pathway alterations. All patients evaluated had previously received surgery, radiation therapy, or both. Patients received an average number of nine cycles of abemaciclib, an agent which is 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 the 6 months after they started therapy. There was no control arm in the study, due to the lack of standard treatment options available for patients with high-grade tumors after surgery and radiation. However, these results compare favorably to previous studies that found that, on average, 0% to 29% of patients with grade 2 or 3 meningiomas had cancer that wasn’t progressing within 6 months from the time they started their experimental treatment. In the Alliance A071401 trial, the median progression-free survival was 10 months and the median overall survival was 29 months. Side effects were similar to what patients taking CDK inhibitors for other cancers experience: diarrhea, fatigue, headache, and nausea/vomiting. About a quarter of patients had grade 3 or grade 4 adverse events that were deemed possibly or likely related to treatment. “We are encouraged by these exciting results, but we still have more work ahead of us to improve treatments for this understudied patient population,” said Dr. Brastianos.