Efficacy and safety of [177Lu]Lu-DOTAGA.FAPi dimer radionuclide therapy in patients with advanced-stage breast cancer

Introduction: Fibroblast activation protein (FAP) expression is markedly upregulated in various cancers and small molecule inhibitors for theranostic applications have gained interest recently. Cancer associated fibroblasts have a direct involvement in the progression of metastatic breast carcinoma with decreased sensitivity to chemotherapy and hormonal therapy [1-7]. The study aimed to assess the safety and efficacy data of [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer radionuclide therapy in patients with advanced-stage breast cancer.

Methods: In this retrospective study from November 2020 to October 2022, heavily pretreated end-stage breast cancer patients were offered [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer radionuclide therapy on compassionate grounds. All patients underwent a prior [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT scan to conform avid FAP expression. A total of 11 metastatic breast cancer patients (10 females, 1 male) with a mean age of 55.6 years (range: 30 - 70 years) were enrolled in the study and underwent [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer. Treatment was repeated every 8 to 12 weekly intervals over a median follow-up duration of 11 months (mo) (range: 4 to 16 mo). The primary endpoint included molecular response assessment by [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT scans according to PERCIST 1 criteria. Safety assessment was conducted according to Common Terminology Criteria for Adverse Events (CTCAEV5.0).

Results: 85% of patients had invasive ductal carcinoma, and 15% had invasive lobular carcinoma. All patients presented with distant metastases on baseline [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT scan. A total of 31 cycles of [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer with a median of 3 cycles (range: 2 - 6) and median administered activity per cycle of 5.5 GBq (range: 2.0 – 9.0 GBq) were used. [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT imaging-based molecular response assessment in 7 patients revealed partial response in 28.5% (2/7), stable disease in 43% (3/7), and disease progression in 28.5% (2/7). 27% (3/11) of deaths occurred during the median follow-up duration of 11 months. Grade III pancytopenia occurred in only one patient. Grade III/IV renal or hepatotoxicities were not observed.

Conclusions: [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer therapy is well-tolerated, safe, and effective in the treatment of end-stage metastatic breast cancer.