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. 2023 Jan 5;30(2):e220236.
doi: 10.1530/ERC-22-0236. Print 2023 Feb 1.

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma

Camilo Jimenez  1 , Bennett B Chin  2 , Richard B Noto  3 , Joseph S Dillon  4 , Lilja Solnes  5 , Nancy Stambler  6 , Vincent A DiPippo  6 , Daniel A Pryma  7
Affiliations

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma

Camilo Jimenez et al. Endocr Relat Cancer. .

Abstract

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.

Keywords: biomarker response; high-specific-activity I-131 MIBG; paraganglioma; pheochromocytoma.

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Conflict of interest statement

NS and VAD are employees of Progenics Pharmaceuticals, Inc., a Lantheus company. CJ, BBC, RBN, JSD, LS and DAP served as investigators for this clinical study.

Figures

Figure 1
Figure 1
Patient flow diagram for the phase 2 trial.
Figure 2
Figure 2
Best biochemical tumor marker response at any time point for (A) total plasma free metanephrines (normetanephrine + metanephrine); (B) total fractionated urinary metanephrines (normetanephrine + metanephrine); (C) plasma free normetanephrine; (D) urinary normetanephrine; (E) plasma free metanephrine; (F) urinary metanephrine; (G) chromogranin A.
Figure 3
Figure 3
Proportion of patients with a biochemical response (CR + PR) at any time point for all patients receiving a therapeutic dose of HSA I-131 MIBG (blue bars) compared to patients who received two doses (red bars). PNM: plasma normetanephrine; UM: urinary metanephrine; PM: plasma metanephrine; UM: urinary normetanephrine.
Figure 4
Figure 4
Individual biochemical tumor marker responses: percentage of patient responders (complete response plus partial response) over time. CgA: chromogranin A; NM: normetanephrines; NE: norepinephrine.
See this image and copyright information in PMC

References

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