Effectiveness, safety, and retreatment outcomes in GEP-NET patients undergoing ¹⁷⁷Lu-based PRRT: a ten-year...

Peptide receptor radionuclide therapy (PRRT) using ¹⁷⁷Lu-labeled somatostatin analogues is an established and increasingly applied treatment for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We report results focusing on effectiveness, short-term safety, and retreatment outcomes, based on ten years of clinical experience from an Austrian center of expertise, including patients referred for retreatment after prior therapy elsewhere.

This retrospective study included 49 patients treated with ¹⁷⁷Lu-DOTATATE or ¹⁷⁷Lu-DOTATOC between 2014 and 2023. Subgroups included patients receiving their first PRRT course at our center (n = 45). Of this initial-treatment cohort, 9 patients subsequently underwent PRRT retreatment at our center. Additionally, 4 external patients previously treated with ⁹⁰Y-PRRT at another institution were referred for ¹⁷⁷Lu-based retreatment, resulting in a total retreatment subgroup of 13 patients. Overall survival (OS), progression-free survival (PFS), and selected laboratory toxicity parameters were evaluated according to CTCAE v5.0.

In the GEP-NET group, the median number of PRRT cycles was 4 with a median cumulative activity of 27.9 GBq. Median OS was 54.2 months (95% CI: 33.2-upper bound not reached), and median PFS was 24.1 months (95% CI: 11.8-36.1). PET-CT-based response assessment was available in 36 of 45 patients. Using evaluable patients as denominator, the exploratory visual SSTR-PET-CT-based objective response rate was 30.6%. Considering the entire initial-treatment cohort and assuming patients without follow-up imaging were non-responders, the ORR was 24.4%. Grade 3 or higher hematologic toxicity occurred in 4.4% of patients with one case each of grade 3 anemia and grade 4 leukopenia while no grade 3 or higher renal toxicity was observed. One patient (2%) developed myelodysplastic syndrome (MDS), followed by acute myeloid leukemia (AML). In the retreatment group (median 4 additional cycles), the median PFS was 18.1 months (95% CI: 8.6-24.6) and the ORR was 30.8% (n = 13). No grade ≥3 toxicities or hematologic malignancies were observed.

PRRT at our institution showed clinical outcomes and a favorable short-term safety profile broadly consistent with previously published PRRT studies. These findings support the role of PRRT in routine clinical practice. Retreatment outcomes appeared encouraging in selected patients but should be interpreted as exploratory given the limited cohort size, retrospective design, and absence of formal comparative analysis.