Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma

Abstract

Introduction: The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [¹⁷⁷Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.

Patients and methods: Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [¹⁷⁷Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [⁶⁸Ga]Ga-FAPI-2286 PET/CT.

Results: After four cycles of PTRT with [¹⁷⁷Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUV_max and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients.

Conclusion: [¹⁷⁷Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.

Keywords: 177 lutetium; FAP-2286; Fibroblast activation protein (FAP); Radionuclide therapy; Sarcoma.