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FDA Approves First Therapy for High-Risk Neuroblastoma
The FDA has approved dinutuximab (Unituxin, United Therapeutics) as part of first-line therapy for pediatric patients with high-risk neuroblastoma, a type of cancer that most often occurs in young children.
Neuroblastoma is a rare cancer that forms from immature nerve cells. It usually begins in the adrenal glands but may also develop in the abdomen, chest, or nerve tissue near the spine. The disease typically occurs in children younger than 5 years of age. According to the National Cancer Institute, neuroblastoma occurs in approximately 1 out of 100,000 children and is slightly more common in boys. An estimated 650 new cases of neuroblastoma are diagnosed in the U.S. each year. Patients with high-risk neuroblastoma have only a 40% to 50% chance of long-term survival despite aggressive therapy.
Dinutuximab is an antibody that binds to the surface of neuroblastoma cells. The drug has been approved for use as part of a multimodality regimen, including surgery, chemotherapy, and radiation therapy, for patients who have achieved at least a partial response to prior first-line multiagent, multimodality therapy.
The FDA had granted dinutuximab both “priority review” and “orphan product” designations. Priority review shortens the timeframe for review of a drug application by 4 months compared with standard reviews and is granted to drugs that, if approved, will provide a significant improvement in safety or efficacy in the treatment of a serious condition. An “orphan product” designation is given to drugs that are intended to treat rare diseases.
The safety and efficacy of dinutuximab were evaluated in a clinical study of 226 pediatric subjects with high-risk neuroblastoma whose tumors shrank or disappeared after treatment with multiple-drug chemotherapy and surgery followed by additional intensive chemotherapy, and who subsequently received bone marrow transplantation support and radiation therapy. The subjects were randomly assigned to receive either dinutuximab in combination with interleukin-2 and granulocyte–macrophage colony-stimulating factor, which are thought to enhance the activity of dinutuximab by stimulating the immune system, or an oral retinoid drug, isotretinoin (RA), alone.
Three years after treatment, 63% of the subjects in the dinutuximab combination group were alive and free of tumor growth or recurrence compared with 46% of the RA group. In an updated analysis of survival, 73% of the subjects who received the dinutuximab combination were alive compared with 58% of those who received RA alone.
The labeling for dinutuximab includes a boxed warning alerting health care professionals and patients that the drug irritates nerve cells, causing severe pain that requires treatment with intravenous narcotics, and can also cause nerve damage and life-threatening infusion reactions, including upper airway swelling, difficulty breathing, and hypotension, during or shortly after the completion of the infusion. Dinutuximab may also cause other serious adverse effects, including infections, eye problems, electrolyte abnormalities, and bone marrow suppression.
The most common adverse effects of dinutuximab in clinical studies included severe pain, fever, low platelet counts, infusion reactions, hypotension, hyponatremia, elevated liver enzymes, anemia, vomiting, diarrhea, low potassium levels in the blood, capillary leak syndrome (which is characterized by a massive leakage of plasma and other blood components from blood vessels into neighboring body cavities and muscles), neutropenia, lymphopenia, hives, and low blood calcium levels.
Source: FDA; March 10, 2015.