In the first genomically driven trial for meningioma patients, an oral drug appeared to slow disease progression in patients with few other options 

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 tumour growth in patients with aggressive meningiomas that have specific genetic mutations.

Results are published in Nature Medicine.

Meningiomas, tumours that grow in the membranes that surround the brain and spinal cord, are the most common primary brain tumours.

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 enrol 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 tumours 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 tumours 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 tumours 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 diarrhoea, 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.

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.

Source: Mass General Brigham