The FDA has approved selumetinib (Koselugo, AstraZeneca) for adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

Selumetinib, an oral kinase inhibitor that targets the mitogen-activated protein kinase (MEK) 1 and MEK2 enzymes, was originally approved in 2020 for children aged 2 years or older with NF1-PN. That approval was expanded in September to pediatric patients aged 1 year or older.

With the new regulatory decision, selumetinib joins another oral MEK inhibitor, mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.), as an option for adults. Mirdametinib was approved by the FDA in February for treating adult and pediatric patients aged 2 years or older who have symptomatic NF1-PN that cannot be completely resected.

In the US, there are 30,000-50,000 people living with NF1-PN, according to SpringWorks.

NF1 is a rare, progressive genetic disorder usually diagnosed in childhood that typically causes soft lumps to form on and under the skin. Patients also commonly develop PNs — nonmalignant nerve sheath tumors — that can cause pain, disfigurement, muscle weakness, and other debilitating symptoms. In a small number of cases, PNs become malignant.

NF1 involves overactivity in the MEK1 and MEK2 enzymes, which stimulate cell growth, and inhibiting them can slow PN growth, according to AstraZeneca.

Selumetinib’s label expansion to adults was based on the KOMET trial involving 145 adults who were randomly assigned equally to receive selumetinib 25 mg/m² twice daily or placebo. After 12 28-day cycles, patients in the placebo group were switched to selumetinib, and patients in the selumetinib remained on treatment for an additional 12 cycles.

At the end of cycle 16, the confirmed overall response rate was 20% in the selumetinib arm vs 5% in the placebo arm, with 86% of selumetinib-treated patients having a duration of response of at least 6 months.

There was also evidence of a greater reduction in chronic pain scores with selumetinib by cycle 12 than with placebo, but the difference did not reach statistical significance (P = .07).

Selumetinib labeling includes warnings and precautions for left ventricular dysfunction; increased creatine phosphokinase; increased levels of vitamin E and heightened bleeding risk; and ocular, gastrointestinal, and skin toxicity.

The recommended selumetinib dose is the same as in KOMET, 25 mg/m² orally twice daily, until disease progression or unacceptable toxicity.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com