Efficacy and safety of high-specific-activity ¹³¹I-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 ¹³¹I-meta-iodobenzyl-guanidine (HSA ¹³¹I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA ¹³¹I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA ¹³¹I-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. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA ¹³¹I-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 ¹³¹I-MIBG. Conclusion: HSA ¹³¹I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.