Therapeutic potential of FAPI RLT in oncology: A systematic review

Rationale: This systematic review aims to examine the safety and efficacy of fibroblast activation protein inhibitor (FAPI) radioligand therapy (RLT) for various epithelial neoplasms. Methods: PubMed, Web of Science, and Scopus databases were searched up to Jan 4, 2025, for studies involving FAPI RLT in various cancers. Data extraction focused on exploring safety and efficacy of FAPI RLT. Results: Overall, 27 studies involving a total of 144 patients who received FAPI RLT were included in this systematic review. [¹⁷⁷Lu]Lu-FAPI was employed in 21 studies, with 225 cycles administered to 95 patients at a median dose of 6.8 GBq/cycle. Six non-randomized clinical investigations using [¹⁷⁷Lu]Lu-FAPI reported disease control rates ranging from 18.2% to 83.3%. Only three studies documented a cumulative total of six patients who experienced grade 3 or 4 toxicity post [¹⁷⁷Lu]Lu-FAPI RLT. Of 16 case reports utilizing [¹⁷⁷Lu]Lu-FAPI, nine achieved disease control across various cancer types, with no reported adverse events. Four studies employed [⁹⁰Y]Y-FAPI, totaling 103 cycles in 42 patients at a median dose of 6.7 GBq/cycle. Three non-randomized clinical investigations reported disease control rates of 50% to 82%, with two studies documenting eight high-grade toxicity events. Furthermore, a successful administration of [⁹⁰Y]Y-FAPI was employed in a single reported case involving multiple primary neoplasms with no reported adverse events. However, the patient did not achieve disease control post [⁹⁰Y]Y-FAPI. A cohort study utilized 53 [²¹³Bi]Bi-FAPI-46 injections following a fractionated dose regimen in six cancer patients, achieving a 33.3% disease control rate without reported adverse events. One case report described dual radionuclide therapy using two cycles with a cumulative 20 GBq [¹⁵³Sm]Sm-FAPI and a third 8 GBq [⁹⁰Y]Y-FAPI cycle in a lung cancer patient, resulting in stable disease for eight months. Conclusion: FAPI RLT is a promising and safe therapeutic agent in oncology, with potential benefits achieved on short-term basis. However, its long-term efficacy and safety require further research with larger, controlled studies, considering the currently observed variations in patient populations, cancer types, and methodologies within reviewed studies.