Fibroblast activation protein (FAP)-targeted radioligand therapy may be safe and effective in patients with progressive metastatic tumors, particularly advanced sarcomas, according to new findings presented by Lanzafame et al at the 2024 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting (Abstract 242169).
Background
FAP is known to be highly expressed on the cancer-associated fibroblasts of several malignant solid tumors and sarcomas. As a result, FAP may demonstrate the potential to be used as a theranostic target for radioligand imaging and therapy.
“FAP-targeted radioligand therapy represents a groundbreaking approach in cancer treatment. Its ability to selectively target electively to FAP-expressing cells and deliver localized radiation, minimizing off-target effects, has the potential to offer significant advantages over traditional therapies,” emphasized lead study author Helena Lanzafame, MD, a researcher in the Department of Nuclear Medicine at University Hospital Essen in Germany.
Study Methods and Results
In the new study, researchers assigned 30 patients with advanced sarcomas; or advanced metastatic pancreatic cancer, prostate cancer, gastric cancer, squamous cell carcinoma, or cholangiocarcinoma to receive a total of 77 cycles of yttrium (Y)-90–FAPI-46 radioligand therapy between June 2020 and December 2023. Following treatment, they assessed adverse events of any grade as well as imaging responses on the basis of RECIST or PERCIST guidelines.
The researchers found that Y-90–FAPI-46 radioligand therapy controlled disease progression in nearly 50% of patients—almost exclusively among those with advanced sarcomas. The treatment was well tolerated, and the critical organ radiation dose levels were not reached during treatment. Imaging control of disease by RECIST was obtained in 44% of the patients—35% of whom had advanced sarcomas. Further, a PERCIST response was noted in 55% of the patients.
Conclusions
“The results of our study have demonstrated good tolerance and promising efficacy, particularly in controlling disease progression in patients with advanced sarcomas,” underscored Dr. Lanzafame. “This indicates a specific benefit for this patient group, who often have limited treatment options [because of] the aggressive nature and poor prognosis associated with metastatic-stage disease. Y-90–FAPI-46 radioligand therapy represents a promising approach for these patients, potentially improving survival rates and quality of life,” she concluded.
Disclosure: For full disclosures of the study authors, visit xcdsystem.com.
