Terapia con radiofármaco ⁹⁰Y-FAPI-46 en sarcoma y otros tumores sólidos: un análisis actualizado de cohortes

Fibroblast activation protein (FAP) is highly expressed in many cancers, especially sarcomas, and represents a promising theranostic target. We present an updated retrospective analysis of ⁹⁰Y-FAP inhibitor (FAPI)-46 treatment in patients with sarcoma or other solid tumors. Methods: We performed monocentric analysis of patients with progressive sarcoma or metastatic cancer who were eligible for ⁹⁰Y-FAPI-46 therapy after approved treatments had been exhausted and who showed high FAP expression (SUV_max, ≥10 in over 50% of lesions on ⁶⁸Ga-FAPI-46 PET). After therapy, ⁹⁰Y-FAPI-46 scintigraphy confirmed distribution and uptake, and serial ⁹⁰Y-FAPI-46 PET/CT scans measured absorbed doses. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. Tumor responses were evaluated using RECIST and PERCIST. Results: Thirty patients-23 (77%) with sarcoma, 3 (10%) with pancreatic cancer, 1 (3%) with prostate cancer, 1 (3%) with gastric cancer, 1 (3%) with nonmelanoma skin cancer, and 1 (3%) with cholangiocarcinoma-received a total of 77 cycles of ⁹⁰Y-FAPI-46 radiopharmaceutical therapy between June 2020 and December 2023 and were followed until death or the last follow-up (April 2024). The median interval between cycles was 5 mo (interquartile range [IQR], 4 mo). Of the 30 patients, 11 (37%) received 4 or more cycles. A median of 3.7 GBq (IQR, 3.7-3.8 GBq) was administered during the first cycle, and a median of 7.4 GBq (IQR, 7.2-7.4 GBq) was administered for subsequent cycles. The mean absorbed dose was 0.48 Gy/GBq (SD, 0.06 Gy/GBq) in the kidneys and 0.04 Gy/GBq (SD, 0.01 Gy/GBq) in the bone marrow. Lesions with the highest uptake absorbed a mean dose of 2.4 Gy/GBq (SD, 1.04 Gy/GBq). After treatment, hematotoxicity of any grade was observed in 20 of 30 (67%) patients. Eight of 30 (27%) patients reached a Common Terminology Criteria for Adverse Events grade of at least 3, experiencing adverse events that included thrombocytopenia in 2 (6%), neutropenia in 2 (6%), anemia in 2 (6%), leukopenia in 1 (3%), and elevated γ-glutamyl transferase in 1 (3%) patient. RECIST (n = 25) and PERCIST (n = 20) responses after treatment were assessed. Disease control according to RECIST was 48% (12/25), including 3 partial responses (12%). Disease control correlated with extended overall survival (median, 14.6 vs. 1.9 mo). Metabolic response per PERCIST was observed in 12 of 20 (60%) patients. Conclusion: With long-term follow-up, the favorable safety profile of ⁹⁰Y-FAPI-46 therapy is confirmed. Nearly half of the patients demonstrated disease stabilization, almost exclusively in sarcomas. Our findings support the role of FAP-directed radiopharmaceutical therapy in patients with metastatic sarcoma.