A multicenter phase I clinical trial of the oral drug selumetinib has shown some early promising results in children diagnosed with neurofibromatosis type 1 (NF1), a common genetic disorder that results in plexiform neurofibromas up to 50 percent of the time.

Plexiform neurofibromas are tumors of the peripheral nerves, which often cause pain, disfigurement and disability.

Early results show that selumetinib was well tolerated and partial tumor shrinkage was seen in over 70 percent of patients.

While a number of trials with other drugs targeting these types of tumors have overall been negative, the new results were a pleasant surprise for researchers led by Brigitte C. Widemann, M.D., of the Pediatric Oncology Branch at the NCI Center for Cancer Research.

In a video about the work Widemann said that even though researchers were hopeful, “we didn’t really, to be perfectly honest, expect it.”

The tumors seen in NF1 are often inoperable, and there is no current treatment that is considered effective.

“Some may say that a 20 percent volume reduction is too small to be meaningful, but to me, just stopping the growth of these devastating tumors is an important achievement,” Widemann said in a statement. “The difference we see in these patients is truly unprecedented.”

The study involved 24 children, 11 girls and 13 boys, who had inoperable plexiform neurofibromas that were growing at a rate of more than 20 percent per year.

After taking selumetinib twice a day for an average of 30 months, most patients experienced tumor shrinkage, which lasted long term, for about two years.

As of 2016 there was no disease progression for any of the participants. Most of the patients are still on the medication, some for a five-year period, with no observable adverse effects. The primary goal the study was to identify the maximum tolerated dose that could be given to the children over a long period of time, and found that most side effects were mild.

The drug, provided by AstraZeneca, is a selective inhibitor of the MEK protein, which is part of RAS signaling pathways. 

Widemann said the long history of work at NCI dedicated to studying these tumors has enabled the researchers to really understand what is going on when new agents are given to patients.

“We’ve developed criteria for how to measure these tumors, so we can sensitively measure changes over time and we’re able to implement meaningful clinical trial designs,” she said in a video about the study.

After dose reductions, some participants experienced a loss of response to selumetinib, so the researchers suggest more studies are needed to understand tumors that stop responding to the drug.

A phase II study is currently enrolling patients to study efficacy of the therapy in children.

“In the future, we may wish to look at intermittent dosing in patients to minimize toxicity and retain maximal outcomes,” Widemann said in a statement.

Results of the study were published Dec. 29 in the New England Journal of Medicine.

Contributing Editor/Science Writer