Efficacy and Safety of High-Specific-Activity I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity I-meta-iodobenzylguanidine (HSA I-MIBG) in patients with advanced PPGL. In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Of the 68 patients who received at least 1 therapeutic dose of HSA I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA I-MIBG. HSA I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.