Pediatric Neurofibromatosis: What's Next for the Rare Tumor Syndrome?

Two researchers spoke about the recent FDA approval for this patient population, and what more needs to be done in the space.

Until recently, there was no FDA-approved therapy for pediatric patients with neurofibromatosis type 1 (NF1), a genetic disorder that causes tumor growth — which could become cancerous – in young children.

On April 10, the FDA approved selumetinib (Koselugo) for children over the age of 2 who have inoperable or symptomatic plexiform (PNs) — tumors on nerve sheaths. NF1-related tumors can drastically impair a patient’s daily function, be incredibly painful, and turn into cancerous tumors as well.

“This is a tumor predisposition syndrome, so it puts kids at risk for development of lots of different kinds of tumors,” Andrea Gross, MD, assistant research physician at the National Cancer Institute (NCI) said. “Some of them are cancer-type tumors, and some of them are not.”

Gross and Brigitte C. Widemann, MD, chief, pediatric oncology branch, immune deficiency and experimental therapeutics section at the NCI, discussed NF1 with Oncology Nursing News in a recent interview.

Selumetinib Brings Landmark Change

Prior to the FDA’s approval of selumetinib, treatment for pediatric NF1 with PNs was purely symptomatic. Patients were given opioids or neuropathic medications to manage their pain, and recommended to participate in physical therapy and other services to help deal with the other issues that the tumors could cause.

Surgery was also an option, but depending on where the tumor is located, it could be difficult or even impossible to get to and runs risks of further complications.

“We’re so excited that for the first time, we actually have a medicine that can help these patients that is now based on clinical trials that we conducted and is FDA approved,” Widemann said, explaining that the approval was based on 2 clinical trials that proved not only that selumetinib is safe to take, but it also shrinks tumors in the majority of patients enrolled.

An Overview of NF1 and the New Drug to Treat It

The disease, which occurs in occurs in about 1 in every 3,000 infants, is brought on by a mutation in the NF1 gene, which acts as a tumor suppressor. When NF1 is not working properly, cells continue to grow and survive and can become tumors.

“Patients with NF1 can either have an inherited mutation from their mom or dad, or a spontaneous mutation in the NF1 gene,” Widemann explained.

But this newly approved agent can now stop the over-production of cells.

“What this medicine does is act like an off switch to the pathway that is overactive,” Gross said. “It plugs the pathway that is too active in that one patient with NF1 so that it is more like a person who doesn’t have NF1.”

More Work Is Needed

While selumetinib is a landmark advance for patients with this rare tumor syndrome, it is not curative. There is still much more work to be done, such as figuring out who may develop PNs.

“If we could start earlier with treatment, I think that would be a major advance for patients. That’s one area we’d like to look at,” Widemann said. “We’re also looking at — and other researchers are too – if we can give other medications or if we can combine medications safely to shrink the tumors more and prevent these tumors.”