Best Children's Hospitals US News & World Report 2025-26
World's Best Specialized Hospitals Newsweek 2026

BOSTON, MA [March 26, 2025] — Pediatric high-grade gliomas, particularly H3K27M diffuse midline gliomas (DMG), are aggressive malignant brain tumors with a poor prognosis. Previous research suggests that platelet-derived growth factor receptor alpha (PDGFRA) appears to play a multifaceted role in the pathogenesis of both adult and pediatric high-grade gliomas. Not only are genetic alterations of PDGFRA common in patients with pediatric high-grade gliomas, but elevated PDGFRA expression has been shown to be key in driving growth of DMG tumors.

Now, findings of a recent multicenter study led by Mariella Filbin, MD, PhD, co-director of the Brain Tumor Center at Boston Children’s Hospital and Dana-Farber Cancer Institute, suggest that PDGFRA could be a potential therapeutic target for pediatric high-grade gliomas. Filbin and her team — including collaborators at the University of Michigan Medical School and the Medical University of Vienna — also provide the first real-world clinical data to support the use of a PDGFRA inhibitor in the treatment of certain pediatric patients with high-grade gliomas.

Pinpointing a potential treatment target

To determine the frequency of PDGFRA alterations in pediatric high-grade gliomas, Filbin and her colleagues analyzed genomic data from 217 pediatric high-grade glioma samples. They identified PDGFRA alterations in nearly 15 percent of patients. Using transcriptomic data, they also found significantly elevated PDGFRA expression in tumors with PDGFRA mutation or amplification.

Next, the team tested the activity of four PDGFRA inhibitors (dasatinib, crenolanib, axitinib, and avapritinib) against a panel of glioma cell lines with PDGFRA alterations. Of these drugs, avapritinib exhibited the highest potency. Additional pre-clinical testing found that avapritinib also had the least amount of off-target kinase activity, suggesting drug is less likely to cause unintended side effects.

Promising early clinical data

Finally, following additional testing in mouse models, the researchers treated eight pediatric and young adult patients who had high-grade gliomas with avapritinib through a compassionate use program. Most of the patients had DMGs, and seven of the eight had PDGFRA alterations. All had previously undergone surgical biopsy or resection and radiation, and four had also received chemotherapy or other treatment approaches.

After being treated with avapritinib once daily for an average of four months, three of the patients demonstrated a radiographic response. The drug was also well tolerated. These three patients also survived roughly twice as long as those who didn’t respond to avapritinib, although their disease ultimately metastasized.

This early data suggests that avapritinib is generally safe and may trigger an initial clinical response in a small group of patients who have pediatric high-grade gliomas with PDGFRA amplification.

“Our research now provides the basis for a clinical trial for avapritinib in newly diagnosed pediatric patients,” says Filbin. “Our follow-up work focuses on genetic markers for personalized treatment and developing combination therapies with FDA-approved drugs to enhance efficacy.”