Endocrine Abstracts

Introduction: Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with no standardised protocol for treatment. ¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is an emerging treatment option for patients with metastatic and/or inoperable PPGL, and with low toxicity. We present our experience with PRRT in advanced PPGL, treated in a ENETS Centre of Excellence.

Materials and Methods: 165 patients with PPGL were screened retrospectively to identify cases with progressive disease and/or inoperable PPGL, treated with 2 or more cycles of ¹⁷⁷Lu-DOTATATE. Clinical (changes in antihypertensive medications or catecholaminergic features), radiological response rate (assessed by review of radiology reports and a formal RECIST assessment will be completed) and biochemical (plasma free metanephrines) responses were evaluated 8-12weeks after the last cycle of PRRT. Toxicity was assessed according to CTCAE v5.0. Progression Free Survival (PFS) was estimated using Kaplan Meier Survival analysis. Median Overall Survival (OS) was not reached.

Results: A total of 19 patients (4 phaeochromocytoma, 15 paraganglioma) were included (age range: 35-84 years, germline SDHx pathogenic variant found in 53%, elevated normetaphrines in 53% at baseline). Median duration of follow up was 30 months(range: 5-114) from the date of cycle 1 of PRRT. Patients received PRRT due to radiological progression 15(79%) or inoperable disease with metastases at baseline 4(21%) (median cycles: 4; median cumulative dose: 24.5 GBq). Radiological response was evaluable in 17 patients with PPGL, which confirmed stable disease in 11 patients (65%), and progressive disease in 6 patients (35%). Of the total cohort, median PFS from the date of the first cycle of PRRT was 32 months (95% CI, 4.61-59.39). Median PFS for the paraganglioma subgroup and inoperable disease at baseline was 30 months (95% CI, 3.67-56.33), 12 months (95% CI, 9.45-14.55) respectively. Median PFS for the patients with progressive disease at baseline, phaeochromocytoma subgroup and OS could not be assessed due to the relatively small patient numbers. Of patients with elevated metanephrines at baseline (10, 53%), anti-hypertensive doses were unchanged in 6 (60%), increased in 2 (20%), and increased transiently in 1 (10%). No CTCAE grade 3/4 cytopenia or nephrotoxicity was seen. One patient received 2 cycles of half standard dose PRRT due to baseline thrombocytopenia but therapy was then suspended due to progressive disease.

Conclusion: PRRT is an effective treatment option for patients with metastatic PPGL with encouraging PFS and low toxicity. It is a feasible alternative to chemotherapy and ¹³¹I-MIBG but prospective and comparative studies are needed.