WASHINGTON -- The on Friday for the treatment of plexiform neurofibromas in children with neurofibromatosis type 1 (NF1).
NF1 is a genetic condition that leads to the growth of tumors throughout the body, that while benign can affect patients' organs and be painful and debilitating. Selumetinib, a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, is indicated for children 2 years and older with symptomatic and inoperable plexiform neurofibromas, tumors of the nerve sheaths.
"[I]n this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life threatening diseases, and their unique needs, a top priority," Richard Pazdur, MD, the FDA's top oncology/hematology official, said in a statement. "For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1."
Approval was based on a phase II study of 50 NF1 patients with inoperable plexiform neurofibromas who received the drug's recommended oral dose (25 mg/m2 twice daily) until disease progression or unacceptable toxicity. Two-thirds of patients achieved a partial response to selumetinib, defined as a 20% reduction in tumor volume on MRI at 6 months, and 82% of these patients had responses lasting a year or more.
Patient-reported quality-of-life scores also improved for 29 patients during treatment, as did parent-reported scores for 45 patients.
NF1 is rare, diagnosed in approximately 1 of every 3,000 children, and anywhere from 30% to 50% go on to develop plexiform neurofibromas.
In its approval announcement, FDA noted that common toxicities in selumetinib trials included gastrointestinal events (nausea and vomiting, abdominal pain, diarrhea), skin and nail reactions (rash, pruritus, dry skin, paronychia), as well as fatigue, fever, headache, musculoskeletal pain, and stomatitis.
The agency also warned on risks of severe side effects such as heart failure, ocular toxicities, increased creatinine phosphokinase (which can lead to rhabdomyolysis), and bleeding.