ABSTRACT: Abstract Introduction: Iobenguane scan positive cancers including pheochromocytoma/paraganglioma (PPGL), neuroblastoma, and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous tumors that arise from neuroendocrine cells. Recently, high-specific-activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG, AZEDRA®) was approved in the US for treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL. We present a pooled analysis of all available clinical trials to further assess the safety profile of HSA I-131 MIBG. Methods: 118 patients from four HSA I-131 MIBG clinical trials (NCT00339131; NCT00458952; NCT00874614; NCT00659984) were included in a pooled analysis for safety assessments. Adverse events (AEs), laboratory tests, number and quantity of HSA I-131 MIBG doses, hypertensive events, blood pressure (BP), heart rate, ECG, and AEs of special interest (AESI) were analyzed using descriptive statistics. Results: Gastrointestinal (GI) toxicities, especially nausea and vomiting, were the most common AEs associated with HSA I-131 MIBG. GI toxicities were not reported after dosimetry doses. GI, blood and lymphatic system, and vascular disorders were higher in PPGL than in neuroblastoma after therapeutic dose 1 when compared to therapeutic dose 2. The incidence of potentially clinically significant changes in BP was similar following dosimetric and therapeutic doses and are consistent with the underlying hypertension associated with PPGL. No spike in systolic and diastolic BP was observed within the first 4 hours of HSA I-131 MIBG administration, and there were no acute hypertensive crises following dosing. A possibly drug-related mild increase in BP within 48 hours of therapeutic dosing was observed in 1 subject with PPGL. Variations in heart rate (>20 beats/min) were higher after therapeutic dose 1 than after other doses. No clinically significant trends were seen in mean ECG results or mean changes from baseline. All patients received at least one concomitant medication. About 40% of patients received ?-blockers, 39% ?-blockers, and about 27% other peripheral vasodilators. 87.3% of patients reported an AESI, defined as AEs that are related to the acute and/or chronic effects of radiation toxicity seen any time post dosing. The most common AESIs were nausea (66.1%), thrombocytopenia (50.0%), fatigue (50.0%), neutropenia (42.4%), and diarrhea (22.9%). The incidence of most AESIs were similar after each therapeutic dose. Conclusions: HSA I-131 MIBG demonstrated a favorable safety profile in iobenguane scan positive cancers. AEs followed an expected pattern comparable to other radioactive therapeutic agents. Most cardiovascular events, including hypertensive events mostly commonly observed in PPGL, were not considered related to HSA I-131 MIBG.
