smahmood@progenics.com

There is an unmet medical need for the treatment of iobenguane scan positive cancers, and especially in patients with advanced pheochromocytoma/paraganglioma (PPGL). High-specific-activity I- 131 meta-iodobenzylguanidine (HSA I-131 MIBG, AZEDRAŽ) is the first and only radioactive therapeutic agent approved for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. Conventional I-131 meta-iodobenzylguanidine (MIBG) therapy has been associated with hematological toxicity in nearly all treated subjects, and up to a 15% incidence of severe acute hypertension including hypertensive crises and tachycardia during or immediately after the infusion. The purpose of this pooled analysis is to characterize the safety and tolerability of HSA I-131 MIBG.

Data from four HSA I-131 MIBG open-label, Phase I and phase II studies (NCT00339131; NCT00458952; NCT00874614; NCT00659984) were pooled for safety analysis with a data cutoff of March 10, 2017. A literature review was conducted on the safety of conventional I-131 MIBG. Demographic and baseline characteristics will be presented with descriptive statistics for continuous variables, and frequencies/percentages for categorical variables. Adverse event (AE) data will be described by disease indication, age, gender, race, treatment with prior conventional I-131 MIBG, number of HSA I-131 MIBG doses, vital signs, electrocardiogram (ECG), laboratory values, reasons for treatment or study discontinuation, and long-term AEs.

The pooled safety population included 118 patients (age range: 3-76 years) who received any dose of HSA I-131 MIBG. Few AEs showed a clear association with age. The incidence of most AEs was similar regardless of gender or race. The incidence of AEs was comparatively higher after the second therapeutic dose; however, the incidences of most serious AEs (SAEs) were similar after each therapeutic dose. No clinically significant trend was seen in ECG changes from baseline. 21 patients (18%) experienced hypertensive events of which treatment-related hypertension/increased blood pressure was reported in 7 (5.9%) patients and treatment-related tachycardia was reported in 6 (5.1%) subjects. Within 48 hours of therapeutic dosing, only one possibly related mild increase in blood pressure was reported as an AE; other changes in blood pressure were not deemed clinically significant by the investigators in this time period. The most common reason for discontinuation was occurrence of an AE(s) (n=11, 9.3%), followed by receiving another anticancer therapy (n=8, 6.8%) and progressive disease (n=7, 5.9%). Thirty-four (28.8%) deaths were reported, two of which (myelodysplastic syndrome and acute myeloid leukemia) were related to late radiation toxicity attributed to HSA I-131 MIBG.

HSA I-131 MIBG was safe and well-tolerated across patients with iobenguane scan positive cancers. As with other similar radioactive therapeutic agents, HSA I-131 MIBG is associated with a predictable pattern of AEs. No serious treatment-related hypertensive events were observed suggesting that HSA I-131 MIBG would be less likely than conventional I-131 MIBG (with a 15% reported rate of severe hypertensive events) to cause acute or subacute severe hypertensive events. With proactive toxicity management, health care practitioners can ensure maximum treatment benefit and mitigate unnecessary treatment discontinuation.

Presenters or authors on this event have been recognized as RSNA Honored Educators for participating in multiple qualifying educational activities. Honored Educators are invested in furthering the profession of radiology by delivering high-quality educational content in their field of study. Learn how you can become an honored educator by visiting the website at: https://www.rsna.org/Honored-Educator-Award/ Lale Kostakoglu, MD, MPH - 2012 Honored Educator