Lu-177 FAP-2286 radiopharmaceutical therapy shows promising effectiveness for treating brain metastases in advanced lung cancer patients who have failed prior treatments, with a 57.1% objective response rate and 92.9% disease control rate in a recent clinical study.
- Lu-177 FAP-2286 achieved a 57.1% objective response rate and 92.9% disease control rate in patients with lung cancer brain metastases
- Median overall survival was 11.0 months and median progression-free survival was 8.0 months, with responders showing significantly longer survival
- The therapy targets fibroblast activation protein (FAP), which is overexpressed on cancer-associated fibroblasts in brain metastatic lesions but negligible in normal brain tissue
- Patients experienced improved neurological symptoms and better quality of life, with no grade III/IV adverse events reported
- Study enrolled 14 advanced lung cancer patients who had failed at least one prior line of radiotherapy, chemotherapy, or targeted therapy
Lutetium-177 (Lu-177) FAP-2286 radiopharmaceutical therapy appears effective for controlling brain metastases in patients with advanced lung cancer, according to a study published November 3 in Scientific Reports.
A group from the Affiliated Hospital of Southwest Medical University in Luzhou, China, prospectively evaluated the intracranial efficacy and safety of systemic Lu-177 FAP-2286 in patients who had failed prior treatments, with findings suggesting the approach offers a promising therapeutic option for this refractory population.
"Brain metastasis from advanced lung cancer represents a formidable clinical challenge, primarily due to the protective [blood brain barrier], the limited efficacy of conventional therapies, and the high risk of debilitating neurological symptoms," the researchers wrote.
Fibroblast activation protein (FAP) is overexpressed on cancer-associated fibroblasts in brain metastatic lesions and expressed negligibly in normal brain tissue, making it an ideal molecular target, according to the authors. In prior work, the group established that Lu-177 FAP-2286 is safe and effective in advanced lung cancer broadly, while outcomes specifically against brain metastases remain insufficiently studied.
To bridge the gap, the researchers enrolled 14 patients with advanced lung cancer with radiologically confirmed brain metastases who had failed at least one prior line of radiotherapy, chemotherapy, or targeted therapy. Patients received Lu-177 FAP-2286 at 7.4 GBq per cycle for a minimum of two cycles (mean, 3.1 cycles). Intracranial short-term efficacy was assessed by RECIST 1.1 and PERCIST 1.0 four weeks after the second cycle, with all brain metastatic lesions designated as target lesions.
Lu-177 FAP-2286 metabolism activity response pre-treatment and post-treatment in patient 2. Pretreatment Ga-68 FAP-2286 PET/CT imaging showed tracer uptake in the right frontal lobe lesion (SUVmax = 3.86, SULpeak = 2.01) (A–D). Pretreatment F-18 FDG-PET/CT imaging showed intense tracer uptake in the right frontal lobe lesion and perilesional edema (E–H). After 2 cycles of Lu-177 FAP-2286 treatment, the lesion significantly resolved, meeting intracranial CMR criteria (I–L). Scientific Reports
Median overall survival (OS) was 11.0 months and median progression-free survival (PFS) was 8.0 months. Patients achieving metabolic response had significantly longer median PFS (9.0 vs. 6.0 months) and OS (13.0 vs. 9.0 months) than non-responders. In secondary results, neurological symptoms and brain-specific quality of life improved significantly, as measured by the EORTC QLQ-BN20 questionnaire, and no grade III/IV adverse events occurred, the researchers reported.
"This integrative approach offers a novel and promising strategy for managing both systemic and intracranial disease burden, particularly for patients with refractory brain metastases who have failed multiple prior therapies and lack effective treatment options," the authors wrote.
Traditionally, brain metastases in these patients have often been viewed as terminal events, with treatment primarily focused on palliative symptom relief, the group noted. However, with advances in systemic and local therapies, growing evidence suggests that active intervention against brain metastases can translate into survival benefits, they added.
The authors called for multicenter randomized controlled trials directly comparing Lu-177 FAP-2286 to standard brain-directed therapies, suggesting that dose-escalation studies may help optimize intracranial dosing regimens and that combinations with immunotherapy nay offer a promising avenue for more durable responses.
The full study is available here.
