Initial Results and Clinical Experiences of [ ¹⁷⁷ Lu]Lu-FAP-2286 for Pleural Metastases: A Single-Center Retrospective Study

Cancer metastasis, particularly to the pleura, signifies advanced disease and poor prognosis. Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts, is a promising therapeutic target. This retrospective study investigates the efficacy and safety of the FAP-targeting radiopharmaceutical therapy [¹⁷⁷Lu]Lu-FAP-2286 in patients with pleural metastases. <b>Methods:</b> Seventeen patients with FAP-positive pleural metastases from various carcinomas, all previously treated with standard therapies, received a median of 2 cycles of [¹⁷⁷Lu]Lu-FAP-2286. Treatment response was assessed using FAP PET/CT, CT, and qualitative FAP SPECT/CT. Overall survival (OS) and progression-free survival were analyzed, and adverse events (AEs) were reported. <b>Results:</b> The disease control rate (nonprogressive disease) was 59%. Median OS was 17.3 mo, and median progression-free survival was 4.1 mo. Patients achieving disease control had a significantly longer OS (20.3 mo) compared with those with progressive disease (6.4 mo, <i>P</i> = 0.004). Response assessments using FAP PERCIST 1.0 and RECIST 1.1 showed a high concordance rate of 86.7%. Treatment was well-tolerated, with no grade 3-4 AEs reported. The most common AEs were manageable grade 1-2 hematologic toxicities. <b>Conclusion:</b> [¹⁷⁷Lu]Lu-FAP-2286 therapy demonstrates promising preliminary efficacy and a favorable safety profile in patients with pleural metastases, achieving notable disease control and survival outcomes. This study provides real-world evidence supporting FAP-targeted radiopharmaceutical therapy as a treatment option for this patient population and suggests FAP-based imaging is useful for response monitoring. Larger, prospective studies are warranted to confirm these findings.