Abstract
An update on overall survival from a multi-center, open-label, pivotal phase 2b study of AZEDRA® (iobenguane I 131) in patients with iobenguane scan positive locally advanced or metastatic pheochromocytoma/paraganglioma (PPGL)
The Journal of nuclear medicine (1978), Vol.60
05/01/2019
Abstract
Background: AZEDRA, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131 MIBG), is indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (PPGL) who require systemic anticancer therapy. Methods: Iobenguane scan positive PPGL patients ineligible for curative surgery, failed prior therapy or not candidates for chemotherapy, and on a stable antihypertensive regimen for tumor-related hypertension, were enrolled. Patients received a dosimetric dose (111-222 MBq) followed by up to two therapeutic doses, each at 296 MBq/kg to a maximum of 18.5 GBq, at least 3 months apart. Patients were followed for 12-months (efficacy period) and an additional 4 years for long-term follow-up. The primary endpoint measured clinical benefit as defined by the proportion of patients with at least 50% reduction of all antihypertensive medications lasting ≥6 months beginning during the efficacy period, including discontinuation. Secondary endpoints included objective tumor response by RECIST and overall survival (OS). Results: Of 81 pts enrolled, 74 pts received a dosimetric dose of AZEDRA. 68 pts received at least one therapeutic dose and 50 received two therapeutic doses. At study entry, 52% (35/68) had prior surgery and systemic therapy (I-131 MIBG and/or chemotherapy) for PPGL. 71% of patients received at least two prior lines of therapy. 50% (32/64) of evaluable pts had lung and/or liver metastases at baseline. The primary endpoint was met by 25% (17/68) (95% CI 16%-37%) of all patients who received at least one therapeutic dose, achieving pre-specified success criteria. The primary endpoint was achieved in 32% (16/50) (95% CI 21%-46%) of patients who received two therapeutic doses. For objective tumor response, patients who received two therapeutic doses achieved partial response and stable disease in 30% and 68% of patients, respectively. As of July 30, 2018, median OS was 41.1 months (95% CI 31.1, 91.2) from time of first therapeutic dose and median survival appeared similar in pts with and without lung/liver metastasis at baseline (43.8 and 41.1 months, respectively) and there are 14 patients in follow up. The most common (≥50%) adverse events were consistent with expected radiation-related risks of nausea, myelosuppression and fatigue. Myelosuppression resolved within 4-8 weeks and without the need for stem cell transplantation. No severe hypertension, hypertensive crises or CV side effects were observed acutely following therapeutic dosing. Conclusions: This study, the largest prospective clinical trial to date. has demonstrated meaningful clinical benefits of AZEDRA treatment in patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy, as measured by reduction in antihypertensive medications and objective tumor response. Greater clinical benefit was observed in patients who received two therapeutic doses.
Details
- Title: Subtitle
- An update on overall survival from a multi-center, open-label, pivotal phase 2b study of AZEDRA® (iobenguane I 131) in patients with iobenguane scan positive locally advanced or metastatic pheochromocytoma/paraganglioma (PPGL)
- Creators
- Daniel PrymaBennett ChinRichard NotoJoseph DillonLilja SolnesJessica JensenTess LinTheresa WhiteNancy StamblerVincent DiPippoSyed MahmoodVivien WongCamilo Jimenez
- Resource Type
- Abstract
- Publication Details
- The Journal of nuclear medicine (1978), Vol.60
- Publisher
- Society of Nuclear Medicine
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984361720902771
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