Preliminary results and clinical experiences of [177Lu]Lu-FAP-2286 for brain metastases in advanced lung cancer

Brain metastases in advanced lung cancer present a therapeutic challenge with limited effective options. Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts within brain metastatic lesions, making it a promising target for radionuclide therapy. This prospective study evaluated the intracranial efficacy and safety of peptide-targeted radionuclide therapy (PTRT) with [ 177 Lu]Lu-FAP-2286 in 14 patients with FAP-expressing advanced lung cancer and radiologically confirmed brain metastases who had failed prior treatments. Patients received [ 177 Lu]Lu-FAP-2286 (7.4 GBq/cycle, ≥ 2 cycles). Intracranial objective response rate was 57.1% and disease control rate was 92.9% by RECIST 1.1, with a metabolic response rate of 64.3% by PERCIST 1.0. Median overall survival was 11.0 months and median progression-free survival was 8.0 months. Patients achieving metabolic response had significantly longer survival. Neurological symptoms and brain-specific quality of life improved significantly, and no grade III/IV adverse events occurred. These findings suggest that systemic [ 177 Lu]Lu-FAP-2286 PTRT is safe and effective for brain metastases in FAP-expressing advanced lung cancer, achieving intracranial tumor regression, symptom relief, and improved quality of life, thereby offering a promising therapeutic option for this refractory population.