Outcomes of Peptide Receptor Radionuclide Therapy with 177 Lu-DOTATATE in Patients with Metastatic Pheochromocytoma and Paraganglioma

Peptide receptor radionuclide therapy (PRRT) has emerged as a promising treatment for metastatic pheochromocytoma and paraganglioma (mPPGL). This study aimed to evaluate PRRT outcomes in patients with mPPGL in a single institution. Methods: Records of patients with mPPGL who received PRRT were retrospectively reviewed. The outcomes of interest were objective response rate (ORR), disease control rate (DCR), symptomatic benefit, hypertension control, and treatment-related toxicity. ORR included complete response and partial response, whereas DCR encompassed complete response, partial response, and stable disease, determined using RECIST 1.1. Symptomatic benefit was defined as patient-reported symptom improvement relative to baseline. Hypertension control was assessed on the basis of adjustments in antihypertensive medication requirements. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 5.0. Overall survival and progression-free survival were also evaluated. Results: Of the 15 patients included in our study, 7 (47%) had paraganglioma and 8 (53%) had pheochromocytoma. The mean follow-up duration was 28.4 ± 19.3 mo. PRRT was the initial systemic therapy in 2 patients (13%), and 2 treated with PRRT (13%) underwent retreatment, receiving 8 cycles. Two patients (13%) discontinued PRRT because of disease progression, and the remaining 13 patients (87%) completed all 4 cycles. The ORR was 27%, and the DCR was 73%, including 7 patients with stable disease and 4 with a partial response. The mean PRRT response duration was 16.2 ± 14.2 mo. A reduction in dose or no escalation of antihypertensive therapy was observed in 13 patients (87%). Ten patients (67%) reported symptom improvement. The most common toxicities were grade 1 or 2 anemia and leukopenia (40%). Grade 3 or 4 hematologic toxicities occurred in 2 patients (13%), including 1 with thrombocytopenia (7%) and 1 with myelodysplastic syndrome (7%). No moderate or severe nephrotoxicity was observed. Hypertensive crises occurred in 2 patients (13%), 1 with a prior history of such events. The median overall survival was 54.8 mo (95% CI, 6.8-102.8 mo), and the median progression-free survival was 26.9 mo (95% CI, 13.3-40.5 mo). Conclusion: Our findings suggest that PRRT remains a therapeutic strategy for mPPGL, is well-tolerated, and may improve cancer-related symptoms. Large-scale prospective studies are needed to validate structural responses and durability.