FDA approved selumetinib (KOSELUGO®, AstraZeneca) for pediatric patients

From the American Society of Clinical Oncology in cooperation with the Food and Drug Administration (FDA) and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields about recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On April 10, 2020, the Food and Drug Administration approved selumetinib (KOSELUGO®, AstraZeneca) for pediatric patients, 2 years of age and older, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

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

Efficacy of selumetinib was investigated in SPRINT (NCT01362803), a National Cancer Institute (NCI) sponsored, open-label, multicenter, single-arm trial in pediatric patients with NF1 and a measurable target PN 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 PN. Morbidities present
in ≥20% of patients included disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction. Patients received selumetinib 25 mg/m2 orally twice a day until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was overall response rate (ORR) as assessed by 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 3-6 months. The ORR was 66% (n=33; 95% 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 ORR was performed using the same response criteria and demonstrated an ORR of 44% (95% CI: 30,59).

The primary safety data were from 74 pediatric patients with NF1 and PN 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.

View full prescribing information for KOSELUGO.

FDA granted this application priority review and Breakthrough Therapy designation. Selumetinib also received fast track and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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