Efficacy and Safety of [177Lu]Lu-DOTAGA.Glu.(FAPi)2 Therapy in Patients with Sarcoma

The aim of this study was to evaluate the efficacy and safety of [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ therapy in patients with sarcoma, a cohort of individuals with limited treatment options and significant disease burden. Methods: This retrospective analysis involved 10 patients with histologically confirmed sarcoma. Patients received a median cumulative activity of 17.5 GBq (range, 6.3-55.5 GBq) of [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ administered over a median of 3 treatment cycles (range, 1-6 cycles). Patient responses were assessed using PERCIST in 6 patients and RECIST 1.1 in 9 patients. The primary endpoint was the disease control rate, defined as complete response, partial response, or stable disease, evaluated through morphologic, molecular, or clinical criteria. Secondary endpoints included progression-free survival, overall survival, and safety. Results: [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ was generally well tolerated. Response assessment using PERCIST indicated a partial response in 33.3% of patients, whereas no objective response was observed in the response assessed with RECIST. Disease control rates were 50% and 22.3% with PERCIST and RECIST, respectively. Disease progression was documented in 7 patients, 3 of whom succumbed to disease-related complications. The median progression-free survival was approximately 5 mo (95% CI, 2.9-7.1 mo), and the median overall survival was 8 mo (95% CI, 5.5-10.5 mo). Conclusion: [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ demonstrated clinical antitumor activity with a manageable safety profile in patients with sarcoma. Further studies with larger cohorts and combination therapies are warranted to optimize therapeutic efficacy and improve outcomes.