BRAF/MEK Inhibitors Show Promise in Pediatric Astrocytoma


Targeted MAPK-pathway inhibitor therapies appear to have reduced tumor sizes in four children’s inoperable astrocytomas-tumors that had progressed despite chemotherapy.

Targeted MAPK-pathway inhibitor therapies appear to have reduced tumor sizes in four inoperable pediatric astrocytomas-brain tumors that had progressed despite chemotherapy, a researcher reported at the 20th Annual Scientific Meeting of the Society for Neuro-Oncology, held November 19–22 in San Antonio, Texas.

All four children “stabilized or improved clinically” on inhibitor therapy, said Catherine Miller, MD, of the department of neurosurgery at the University of Minnesota in Minneapolis. Inhibitor therapies were “safe, with minimal adverse reactions,” she reported.

“MEK inhibitors and BRAF inhibitors in tumors with BRAF mutations are effective in decreasing tumor volume,” said Miller. “Tumor volume measurement is a reasonable method for documenting response.”

Brain tumors are the most common type of solid tumor in children, and astrocytomas represent the largest pediatric brain cancer population. BRAF gene mutations are “prevalent” in pediatric astrocytomas, Dr. Miller noted.

“Surgery is often the treatment of choice, but complete surgical resection is not always possible,” she noted.

Dr. Miller described four children with inoperable astrocytomas, who had tested positive for MAPK-pathway mutations and were prescribed either vemurafenib or trametinib. After 105 to 805 days on inhibitor treatment, radiographic tumor-volume declines had ranged from 18% to 50%, she reported, with a direct correlation between time on inhibitor therapy and the percentage of decline in tumor volume.

“The longer the patient is on inhibitor therapy, the greater the decrease in tumor volume,” she said.

The patient on therapy for the longest has seen “near complete” radiographic resolution of his brain lesion. That patient, a 23-month-old boy whose tumor harbored a BRAF V600E 1799A point mutation, was administered the BRAF inhibitor vemurafenib. The three other children’s tumors harbored BRAF 7q34 duplication mutations and were prescribed the MEK inhibitor trametinib.

BRAF and MEK inhibitors have been studied for numerous cancers but there is only one ongoing clinical trial for each inhibitor in childhood cancers, she said.

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