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FDA Approves Selumetinib for Pediatric Patients With NF1 and Symptomatic Inoperable Plexiform Neurofibromas


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On April 10, the U.S. Food and Drug Administration (FDA) approved selumetinib (Koselugo) for pediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic inoperable plexiform neurofibromas.

Selumetinib, a kinase inhibitor, is the first therapy approved for pediatric patients who have this rare disease. 

SPRINT Trial
Efficacy of selumetinib was investigated in SPRINT, a National Cancer Institute (NCI)-sponsored, open-label, multicenter, single-arm trial in pediatric patients with NF1 and a measurable target plexiform neurofibroma that could not be surgically removed without risk of substantial morbidity. Patients in the efficacy population (n = 50) were also required to have at least one significant morbidity related to the target plexiform neurofibroma. Morbidities present in ≥ 20% of patients included disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction.

Patients received oral selumetinib at 25 mg/m2 twice a day until disease progression or unacceptable toxicity. The primary efficacy outcome measure was overall response rate as assessed by the NCI and defined as the percentage of patients who experienced ≥ 20% reduction in tumor volume on magnetic resonance imaging (MRI) confirmed on a subsequent MRI within 3 to 6 months.

Results

The overall response rate was 66% (n = 33; 95% confidence interval [CI] = 51–79). All patients had a partial response, and 82% of responders had sustained responses lasting at least 12 months. An independent central review of overall response rate was performed using the same response criteria and demonstrated an overall response rate of 44% (95% CI = 30–59).

The primary safety data were from 74 pediatric patients with NF1 and plexiform neurofibromas who received selumetinib during SPRINT. The most common adverse reactions (≥ 40% of patients) were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, fever, acne, stomatitis, headache, paronychia, and pruritus.

Selumetinib can also cause cardiomyopathy, ocular toxicity including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision, and increased creatinine phosphokinase. Selumetinib should be withheld, dosage reduced, or permanently discontinued based on the severity of adverse reactions.

The recommended selumetinib dose is 25 mg/m2 orally twice a day on an empty stomach until disease progression or unacceptable toxicity.

Richard Pazdur, MD

Richard Pazdur, MD

“Everyone’s daily lives have been disrupted during the COVID-19 pandemic, and in 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. We continue to expedite product development for these patients,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

“We are committed to regulatory flexibility and providing extensive guidance to industry in an effort to bring drugs forward that fulfill unmet medical needs. Selumetinib represents this commitment,” noted Dr. Pazdur. “For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1.”


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