177Lu-FAP-2286 Targeted Radionuclide Therapy in Advanced Pancreatic Cancer

PURPOSE: To evaluate the efficacy, safety, and survival outcomes of 177Lu-FAP-2286 targeted radionuclide therapy (TRT) in patients with refractory or treatment-ineligible pancreatic cancer. PATIENTS AND METHODS: This retrospective single-center study included 22 patients with pancreatic malignancies treated with 177Lu-FAP-2286 between September 2023 and April 2025. Endpoints included safety (CTCAE v5.0), symptom scores, performance status, EORTC QLQ-C30, radiologic response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 34 treatment cycles (median: 1; range: 1-4) were administered. The therapy exhibited a favorable safety profile; the patient-level incidence of treatment-emergent bone marrow suppression and hepatotoxicity was 18.2% and 27.3%, respectively. Grade 3 hematological toxicity occurred in only 9.1% (2/22) of patients with severely compromised baseline reserves, with no grade 4 events observed for any toxicity type. Significant improvements were documented in NRS pain scores (P<0.001), KPS (P<0.001), and multiple EORTC QLQ-C30 functional domains. In the intent-to-treat population, the disease control rate (DCR) was 40.9% (9/22), whereas a higher DCR of 75% (9/12) was observed in the evaluable subgroup. The median OS and PFS for the entire cohort were 127 days (95% CI: 95-254) and 109 days (95% CI: 66-210), respectively. Univariate analysis showed that post-treatment KPS improvement was associated with OS (HR=0.30, P=0.018) and PFS (HR=0.35, P=0.043). CONCLUSIONS: 177Lu-FAP-2286 demonstrated favorable safety and meaningful symptom palliation in refractory pancreatic cancer, supporting further clinical investigation as a salvage therapeutic option.