A national clinical trial led by the Alliance for Clinical Trials in Oncology has found that abemaciclib, an oral cancer drug, may slow tumor growth in patients with aggressive meningiomas that have specific genetic mutations. This primary analysis of Alliance A071401 is published in Nature Medicine .
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 senior author Priscilla Brastianos, MD, 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, a CDK inhibitor that is currently approved for certain breast cancers.
Of the first 24 patients treated with abemaciclib, 58% had high-grade tumors that didn't progress within the six 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%-29% of patients with grade 2 or 3 meningiomas had cancer that wasn't progressing within six 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. Common side effects included diarrhea, fatigue, headache, and nausea/vomiting. About a quarter of patients had a severe side effect (grade 3 or grade 4) that was 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.
In addition Mass General Brigham Cancer Institute, investigators for this study included scientists from the Alliance Protocol Operations, Alliance Statistics and Data Management Center, Columbia University Medical Center, Dartmouth Hitchcock Medical Center, Inova Schar Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Rush University Medical Center, Smilow Cancer Hospital Care Center, UC San Diego Health, University of Iowa, University of Michigan Health West, University of Mississippi Medical Center, University of New Medical Cancer Center, University of Vermont Medical Center, UPMC Hillman Cancer Institute, Wake Forest University, and Weill Cornell Medical Center.
This study was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. It was led and conducted by the Alliance for Clinical Trials in Oncology with participation from the National Clinical Trials Network, both funded by NCI, as part of a collaboration with AstraZeneca, Eli Lilly and Company, GSK, Damon Runyon Cancer Research Foundation, and Alexandra Drane.
