The FDA approved dinutuximab (Unituxin; United Therapeutics), an antibody that binds to the surface of neuroblastoma cells, as part of first-line therapy for pediatric patients with high-risk neuroblastoma. This rare cancer occurs mainly in children aged ?5 years; they have a 40% to 50% chance of long-term survival despite therapy.
The FDA approved dinutuximab to be used as part of a multimodality regimen that includes surgery, chemotherapy, and radiation therapy in patients who had at least a partial response to previous first-line multimodality therapy.
“Unituxin marks the first approval for a therapy aimed specifically for the treatment of patients with high-risk neuroblastoma,” said Richard Pazdur, MD, Director of the FDA’s Office of Hematology and Oncology Products. “Unituxin fulfills a critical need by providing a treatment option that prolongs survival in children with high-risk neuroblastoma.”
Dinutuximab was approved under the FDA’s priority review process and was designated as an orphan drug. Furthermore, the FDA issued a rare pediatric disease priority review voucher to the manufacturer for a subsequent drug application for this drug. This is the second rare pediatric disease priority review voucher granted by the FDA since the inception of this voucher program, which is designed to encourage the development of new therapies for rare pediatric diseases.
The safety and efficacy of dinutuximab were demonstrated in a clinical trial of 226 pediatric patients with high-risk neuroblastoma. The patients were randomized to the oral retinoid drug isotretinoin or to dinutuximab in combination with interleukin-2 and granulocyte-macrophage colony-stimulating factor, which enhance the activity of dinutuximab. After 3 years of treatment, 63% of patients receiving the dinutuximab combination were free of tumor growth or disease recurrence compared with 46% of patients receiving isotretinoin. In addition, the survival rate was 73% versus 58%, respectively, in an updated analysis.
The most common side effects associated with dinutuximab were severe pain, fever, low platelet counts, infusion reactions, hypotension, hyponatremia, elevated liver enzymes, anemia, vomiting, diarrhea, low potassium levels, capillary leak syndrome, neutropenia, lymphopenia, hives, and low blood calcium levels. Dinutuximab is associated with serious adverse events; it was approved with a boxed warning about its potential for irritating nerve cells, causing severe pain, as well as nerve damage and life-threatening infusion reactions. (March 15, 2015)
The FDA granted a breakthrough therapy designation for rindopepimut (Celldex Therapeutics), an investigational immunotherapy vaccine, for the treatment of adults with glioblastoma and the epidermal growth factor receptor (EGFR) variant III (EGFRvIII), which promotes cancer growth. The EGFRvIII mutation occurs in 25% to 40% of glioblastoma cases; the presence of this mutation is associated with poorer prognosis than glioblastoma without the mutation.
The FDA’s designation was based on data from 3 phase 2 clinical trials of patients with newly diagnosed or recurrent EGFRvIII-positive glioblastoma. In these trials, rindopepimut prolonged overall survival beyond what has been achieved in this difficult-to-treat patient population with other treatments. One of these trials was the ACT III phase 2 clinical trial. In ACT III, the overall survival was 21.8 months in patients receiving the vaccine compared with 16 months in the arm of historical control patients. Furthermore, the results of the 3 phase 2 trials showed that rindopepimut is also well-tolerated. The results of ACT III have shown that immunotherapy may be effective in targeting the brain.
Discussing this vaccine, David A. Reardon, MD, Coinvestigator of ACT III and Clinical Director of the Center for Neuro-oncology at the Dana-Farber Cancer Institute in Boston, MA, said, “The bottom line is that patients survive longer….This is the first vaccine that has actually shown a survival benefit for patients.” Dr Reardon added, “Six months may not sound like a big improvement, but for people who are familiar with this type of cancer, people who’ve been doing research and trying to come up with a better treatment, 6 months is a huge improvement.” (February 23, 2015)
