A radiotherapy drug that treats the rare neuroendocrine cancers, pheochromocytoma and paraganglioma, can be both effective and safe for patients, according to the findings of a multicenter trial led by researchers in the Abramson Cancer Center of the University of Pennsylvania. The study showed AZEDRA (ultratrace iobenguane I131) led to a significant reduction in the cardiovascular side effects that are associated with these cancers, while also stopping tumor growth. The drug is designed to treat malignant, recurrent, or unresectable forms of the cancers—cases for which there are currently no approved nonsurgical treatments. Progenics Pharmaceuticals, which manufactures AZEDRA, recently submitted the findings of this trial as part of an application for approval to the US Food and Drug Administration.

The study’s principal investigator Daniel A. Pryma, MD, an associate professor of radiology and radiation oncology, and chief of nuclear medicine and clinical molecular imaging at Penn’s Perelman School of Medicine, will present the results at the American Society of Clinical Oncology 2018 Annual Meeting in Chicago.

“This represents real hope for patients, since as of right now, there are no antitumor therapies available for patients with these tumors who are not candidates for surgery,” Pryma said.

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% of cases metastatic or locally invasive at diagnosis. In addition, when the disease returns, it may not be resectable surgically. The 5-year survival rate of unresectable cases can be as low as 12%.

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 US.

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% in patients who received two doses. That clinical benefit was measured by a 50% or greater reduction in the amount of hypertensive medications these patients took, lasting at least 6 months, as high blood pressure and associated cardiovascular side effects are a major cause of harm from these cancers. Additionally, 92% of evaluable patients who received at least one dose achieved a partial response or stable disease.

“Our data show this therapy provides a dual benefit to patients by not only controlling the tumor, but also the debilitating symptoms caused by their excess hormone production,” Pryma said.

The drug was generally well-tolerated, with the most common side effects being consistent with what a patient would experience with radiation, such as decreased blood counts, fatigue, nausea, and dizziness.

The trial was supported by Progenics Pharmaceuticals, Inc.