Efficacy and Safety of High-Specific-Activity ¹³¹I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma

Abstract

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 131 I-meta-iodobenzylguanidine (HSA 131 I-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 131 I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131 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. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131 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 131 I-MIBG. Conclusion: HSA 131 I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

Phase 2 study of pembrolizumab in patients with advanced rare cancers

“…33 High-specific-activity meta-iodine benzyl guanidine (MIBG) is the only FDA-approved systemic therapy for the treatment of these patients, and it is only effective for the roughly half of patients with MIBG-avid Open access tumors. 34 Treatment with the chemotherapeutic agents cyclophosphamide, vincristine, and dacarbazine is at best palliative and is associated with a clinical benefit in approximately 37% of patients. 35 Several antiangiogenic agents, such as sunitinib, pazopanib, axitinib, and cabozantinib, are under investigation.…”

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

“…Pandit-Taskar and Modak (2017) have presented an overview of NET as a target for theranostics, with a particular focus on the current role and broader application of MIBG and its analogues in neuroendocrine tumors. Very recently, based on the clinical study MIP-IB12B (NCT00874614), the Food and Drug Administration of the US has approved 131 I-MIBG (AZEDRA, Progenics Pharmaceuticals, Inc.) for the anticancer therapy of adult and pediatric patients (12 years and older) with pheochromocytoma (PCC) or paraganglioma (PGL) (Pryma et al 2019 (Chen et al 2015. b The CNS NET tracers derived from antidepressants.…”

Analysis of quantitative [I-123] mIBG SPECT/CT in a phantom and in patients with neuroblastoma

“…Additionally, quantitative SPECT may be useful in the evaluation of recurrent or metastatic phaeochromocytoma, conditions with limited therapeutic options. High specific activity [I-131]-mIBG (Azedra) has received FDA approval for treatment of patients 12 and older with mIBG positive unresectable, locally advanced or metastatic phaeochromocytoma or paraganglioma [24,25]. This treatment may result in reduction in antihypertensive medications and objective tumor response by radiographic criteria.…”