Targeted Therapy Shows Promise for Patients with Aggressive Meningiomas

A national clinical trial led by investigators at Mass General Brigham Cancer Institute through the Alliance for Clinical Trials in Oncology, a leading NCI National Clinical Trials Network group, has found that abemaciclib, an oral cancer drug, may slow tumor growth in patients with aggressive meningiomas that have specific genetic mutations. Results are 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 Mass General Brigham Cancer Institute. Noting that the trial was the first national study to enroll patients based on mutational testing, 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,” says Brastianos.

Authorship: In addition to Brastianos, Mass General Brigham authors include Elizabeth R. Gerstner, A. John Iafrate, Maria Martinez-Lage, Stefan Kaluziak, Elizabeth Codd, Daniel P. Cahill, Sandro Santagata, and Frederick G. Barker II. Additional authors include Katharine Dooley, Susan Geyer, Timothy J. Kaufmann, Mohammed Milhem, Mary Roberta Welch, Thomas J. Kaley, Jan Drappatz, Amy Chan, Priya Kumthekar, Carlos Kamiya Matsuoka, Roy E. Strowd, Adam L. Cohen, Kurt Jaeckle, Lindsay Robell, Rajiv S. Magge, Joo Yeon Nam, Nicholas Blondin, Nawal Shaikh, Ian Rabinowitz, Alissa A. Thomas, David E. Piccioni, Paul Brown, and Evanthia Galanis.

Disclosures: Brastianos has consulted for Voyager Therapeutics, Tesaro, SK Life Science, Sintetica, Pfizer, Merck, ElevateBio, Dantari, Angiochem, MPM, Medscape, Kazia, InCephalo, Genentech, Eli Lilly, CraniUS, Axiom, Atavistik and Advise Connect Inspire, serves on the Scientific Advisory Board for Kazia, Selectin Therapeutics (with equity) and CraniUS, and has received Speaker’s Honoraria from Genentech and Pfizer. She has received institutional research support (to MGH) from Kinnate, Mirati, Merck and Eli Lilly. Additional authors' disclosures can be found in the paper.

Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA189960, UG1CA189824, UG1CA232760, UG1CA233180, UG1CA233184, UG1CA233290, UG1CA233329, UG1CA189816, UG1CA189856, UG1CA233160, UG1CA233323, UG1CA233337; U10CA180868 and UG1CA189867 (NRG Oncology); and U10CA180888. Also supported in part by funds from AstraZeneca, Eli Lilly and Company, GSK, Damon Runyon Cancer Research Foundation and a philanthropic grant from Alexandra Drane. Brastianos receives funding from the NIH, America Association for Cancer Research, Terry and Jean de Gunzburg MGH Research Scholar Award, Breast Cancer Research Foundation, National Brain Tumor Society, the Hellenic Women’s Club (Demetra Fund) and Alexandra Drane. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. https://acknowledgments.alliancefound.org

Paper cited: Brastianos PK et al. “Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial” Nature Medicine DOI: 10.1038/s41591-025-04141-4