Aim <p>Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [¹⁷⁷Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.</p> Materials and methods <p>A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease. Safety was assessed by renal and haematological parameters at 3 months post R-PRRT (CTCAE v5.0). Molecular imaging response was evaluated on [⁶⁸Ga]Ga-DOTA-Octreotate (GaTate) PET/CT using pre-defined criteria. RECIST 1.1 responses 3 months post R-PRRT were documented when feasible. Progression-free and overall survival analysis were performed.</p> Results <p>A total of 63 patients had R1-PRRT (1–3 cycles). The majority (70%) had Grade 2 NET and small intestinal primary (51%). A second re-treatment course (R2-PRRT) was given in 20 patients and a third course (R3-PRRT) in 6 patients. Glomerular filtration rate (GFR) was stable following R1-PRRT. Following R2-PRRT, worsening GFR from CTCAE G2 to G3 was seen in 10% (2/20) of patients, but none after R3-PRRT. Grade 3 thrombocytopenia occurred in 2 patients after R1-PRRT and in 1 patient after R3-PRRT. Grade 4 thrombocytopenia was observed in 1 patient post R1-PRRT. Following R1-PRRT, RECIST 1.1 responses CR, PR, SD was 0%, 10%, 76%, respectively. Disease control rate on GaTate PET/CT was 52/58 (89%) post R1-PRRT. Median progression free survival (PFS) following R1-PRRT was 1.6 years (95% CI:1.2–2.3).</p> Conclusion <p>R-PRRT is feasible, tolerable and efficacious in achieving disease control in patients with progressive GEP NET.</p>