Long-Term Outcomes in Radioiodine-Resistant Follicular Cell-Derived Thyroid Cancers Treated with [ <sup>177</sup> Lu]Lu-DOTAGA.FAPi Dimer Therapy
Sanjana Ballal, Madhav Prasad Yadav, Swayamjeet Satapathy, Frank Roesch, Kunal Ramesh Chandekar, Marcel Martin, Mohammad Shakir, Shipra Agarwal, Sameer Rastogi, Euy Sung Moon, Chandrasekhar Bal
Abstract
Aim: The study aimed to analyze the long-term outcomes of [ 177 Lu]Lu-DOTAGA.FAPi dimer therapy in individuals diagnosed with radioiodine-resistant (RAI-R) follicular cell-derived thyroid cancer. Materials and Methods: In this retrospective study, 73 patients with RAI-R follicular thyroid carcinoma who had undergone multiple lines of previous treatments were included. Following [ 68 Ga]Ga-DOTA.SA.FAPi positron emission tomography–computed tomography scan, among the 73 patients, 65 received [ 177 Lu]Lu-DOTAGA.FAPi dimer monotherapy with a median activity of 5.5 GBq per cycle at 8-week intervals. The remaining eight patients underwent tandem [ 177 Lu]Lu/[ 225 Ac]Ac-DOTAGA.FAPi dimer therapy, consisting of a median of two cycles of [ 177 Lu]Lu-DOTAGA.FAPi dimer followed by one cycle of [ 225 Ac]Ac-DOTAGA.FAPi dimer, also at 8-week intervals. The primary endpoint included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included PERCIST criteria response assessment and safety assessment according to Common Terminology Criteria for Adverse Events (V5.0). Results: We enrolled 37 female and 36 male patients, with a mean age of 54.3 years (range: 27 − 80 years). The patients received a median cumulative activity of 22.2 GBq (range, 4 GBq–55.5 GBq) of [ 177 Lu]Lu-DOTAGA-FAPi dimer over one to nine cycles, with a median of three cycles. Among 73 patients, 20 died and 16 deaths were due to thyroid cancer. Nineteen patients experienced disease progression, with an estimated median PFS of 29 months [CI 14–34 months]. The estimated median OS was 32 months [CI 21–40 months]. Four patients (5.4%) encountered grade III anemia, primarily linked to bone metastasis in three cases and neck tumor mass bleed in one. Grade III thrombocytopenia occurred in three patients (4%). No grade III renal or hepatotoxicity was observed. Conclusion: In this study, [ 177 Lu]Lu-DOTAGA.FAPi dimer therapy showed promising safety and efficacy in aggressive, radioiodine-resistant thyroid cancer, achieving a median PFS and OS of 29 and 32 months, respectively, with manageable adverse events. Confirmation of our findings is needed from prospective clinical trials comparing [ 177 Lu]Lu-DOTAGA.FAPi dimer therapy to other treatments.