FDA approves first ever non-surgical treatment for rare neuroendocrine cancers

The U.S. Food and Drug Administration (FDA) has approved the first ever non-surgical treatment for the rare neuroendocrine cancers pheochromocytoma and paraganglioma. The approval was based on a multi-center trial led by researchers in the Abramson Cancer Center of the University of Pennsylvania and was granted to Progenics Pharmaceuticals for AZEDRA (iobenguane I131).

"This is a true breakthrough. Until today, there were no anti-tumor therapies available for patients with these tumors who were not candidates for surgery," said the trial's principal investigator Daniel A. Pryma, MD, an associate professor of Radiology and Radiation Oncology, chief of Nuclear Medicine and Clinical Molecular Imaging at Penn's Perelman School of Medicine, and a member of Penn's Abramson Cancer Center.

AZEDRA is a targeted, high-specific-activity radiotherapeutic, indicated for the treatment of adult and pediatric patients (12 years and older) with a positive iobenguane scan, and unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy. AZEDRA is the first and only approved therapy for this indication.

Pheochromocytoma and paraganglioma are neuroendocrine tumors that form from the same type of tissue. Pheochromocytoma forms in the adrenal gland, while paraganglioma forms outside of the gland. There are an estimated 650 to 2,600 new cases in the United States each year, with between 10 and 35 percent of cases metastatic or locally invasive at diagnosis. In addition, when the disease returns, it may not be resectable surgically. The five-year survival rate of unresectable cases can be as low as 12 percent.

AZEDRA is a radiotherapy drug that attacks these tumors with a high, specifically-targeted dose. The FDA gave it an Orphan Drug designation, Fast Track status, and Breakthrough Therapy designation in the U.S.

In the Penn-led trial, 68 patients received at least one therapeutic dose of AZEDRA. Twenty-five percent of patients who received at least one dose met the trial clinical benefit endpoint, and the number jumped to 32 percent in patients who received two doses. That clinical benefit was measured by a 50 percent or greater reduction in the amount of hypertensive medications these patients took for at least 6 months, as high blood pressure and associated cardiovascular side effects are a major cause of harm from these cancers. Additionally, 92 percent of evaluable patients who received at least one dose achieved a partial response or stable disease.

"This therapy not only controls the tumor, but also the debilitating symptoms caused by their excess hormone production, meaning it provides a dual benefit to patients," Pryma said.

Pryma noted that Penn is one of the few academic medical centers in the country that has a dedicated tumor board for these rare cancers, making it an ideal institution to lead the multi-center trial. In fact, this is the second FDA approval in which the center has played a role this year. In January, the FDA approved Lutathera (lutetium Lu 177 dotatate) for the treatment of gastroenteropancreatic neuroendocrine tumors which originate in the pancreas or gastrointestinal tract.

"Penn's multidisciplinary approach draws on our physicians' extensive experience in dealing with rare tumors and brings multiple experts from varying backgrounds together to offer cutting-edge treatments," said David C. Metz, MD, the co-director, with Debbie Cohen, MD, of the Neuroendocrine Tumor Center at Penn.

"This is a very exciting step in bringing a much needed treatment to patients with metastatic pheochromocytomas and paragangliomas where limited treatment options exist," Cohen said.