177Lu-FAP-2286 Radioligand Therapy in End-Stage Metastatic Cancer: a promising theranostic approach

<title>Abstract</title> <p> <bold>Purpose:</bold> This study aimed to evaluate the efficacy, safety, and prognostic value of fibroblast activation protein (FAP)-targeted radioligand therapy (RLT) using ¹⁷⁷ Lu-FAP-2286 in patients with end-stage metastatic cancer. <bold>Patients and Methods:</bold> In this single-center retrospective study, 31 patients with end-stage metastatic cancer who had exhausted standard therapies were enrolled. All patients underwent baseline ⁶⁸ Ga-FAP-2286 and ¹⁸ F-FDG PET/CT imaging within a two-week interval. Patients received 2–5 cycles of ¹⁷⁷ Lu-FAP-2286 RLT (7.4 GBq per cycle). Treatment response was assessed using RECIST 1.1 criteria. Safety was evaluated via CTCAE v5.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. <bold>Results:</bold> The disease control rate (DCR) was 38.7% (9.7% partial response, 29.0% stable disease). The median PFS was 5.1 months (95% CI: 2.9–7.3), and median OS was 14.2 months (95% CI: 10.2–13.8). Patients achieving disease control had significantly longer OS compared to those with progressive disease (21.1 vs. 12.0 months, <italic>P</italic> =0.015). Baseline ⁶⁸ Ga-FAP-2286 PET parameters, including FAP-avid tumor volume (FTV) and total lesion FAP expression (TLF), were independent prognostic factors for OS. Hematologic toxicities were most common (anemia: 74.2%, all grades), with a low incidence of grade ≥ 3/4 adverse events (12%). No treatment-related deaths occurred. <bold>Conclusions:</bold> ¹⁷⁷ Lu-FAP-2286 RLT is a feasible and relatively safe therapeutic option for end-stage metastatic cancer, demonstrating meaningful disease control and survival benefits in a heavily pretreated cohort. Baseline ⁶⁸ Ga-FAP-2286 PET/CT parameters (FTV, TLF) hold prognostic value and may aid in patient selection for FAP-targeted therapy. </p>