The US Food and Drug Administration (FDA) today approved iobenguane I 131 (Azedra, Progenics Pharmaceuticals) for the treatment of pheochromocytoma or paraganglioma, which are rare neuroendocrine tumors of the adrenal gland and other tissue areas.
The approval is for locally advanced, unresectable tumors as well as metastatic disease, in both adults and adolescents (≥ age 12) who need systemic therapy.
The radioactive systemic agent or radiopharmaceutical is administered by intravenous injection and is the first FDA-approved drug in this setting.
Arising in the adrenal gland, pheochromocytomas increase the gland's production of the stress hormones epinephrines and norepinephrines, leading to hypertension and a variety of other symptoms such as headaches, irritability, and sweating. Paragangliomas are the same type of neuroendocrine tumor but occur outside the gland.
The efficacy of iobenguane I 131 was demonstrated in a single-group, open-label, phase 2 clinical trial with 68 patients who were ineligible for curative surgery, failed prior therapy, or were not candidates for chemotherapy. A total of 17 patients (25%) experienced a 50% or more reduction of all antihypertensive medications lasting for at least 6 months or longer, which was the primary endpoint.
The FDA also reports that 15 patients (22%) had an objective response, as measured by imaging and RECIST criteria, which was the secondary endpoint.
Most of the study patients (71%) had pheochromocytomas.
Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, placed the drug and its use in context.
"Many patients with these ultra-rare cancers can be treated with surgery or local therapies, but there are no effective systemic treatments for patients who experience tumor-related symptoms such as high blood pressure," Pazdur said in a press statement.
"Patients will now have an approved therapy that has been shown to decrease the need for blood pressure medication and reduce tumor size in some patients," he said.
The most common severe adverse effects reported in clinical trials include lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased international normalized ratio, nausea, dizziness, hypertension, and vomiting.
In the study, iobenguane I-131 was given at an initial dosimetric dose of 111 to 222 MBq at the time of enrollment, which was followed by a therapeutic dose of 296 MBq/kg.
More information about the approval can be found on the FDA website.
Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc
Cite this: FDA Approves Iobenguane I 131 (Azedra) for Rare Neuroendocrine Tumors - Medscape - Jul 30, 2018.