Objective Fibroblast activation protein (FAP) is a promising cancer theranostic target. While FAP-based diagnostics have proven highly accurate, the efficacy and safety of FAP-targeted radioligand therapy (FAP-RLT) for advanced, treatment-refractory solid tumours are poorly characterized. Methods We performed a systematic review and meta-analysis of clinical trials reporting therapeutic outcomes and adverse events of FAP-RLT up to 25 January 2025 (PubMed, ClinicalTrials.gov, Cochrane Library, Web of Science/MEDLINE). Primary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of grade ≥ 3 adverse events. Results The objective response rate of FAP-RLT treatment was 11.7% (95%CI: 3.2%-23.2%; p < 0.001), and the disease control rate reached 44.4% (95%CI: 25.2%-64.5%; p = 0.004). Specifically, peptide ligands demonstrated superior therapeutic efficacy compared to small molecule ligands. Among radionuclides, 177 Lu exhibited better outcomes than 90 Y. In specific tumour types, patients with iodine-refractory thyroid cancer derived the greatest benefit from FAP-RLT, followed by those with lung cancer, sarcomas, and breast cancer. Conversely, patients with colorectal cancer and pancreatic cancer exhibited limited therapeutic responses. The pooled median overall survival was 7.26 months, while the median progression-free survival was 4.77 months. Grade ≥ 3 adverse reactions were observed in 2.2% (95%CI: 0.1%-6.0%; p = 0.018) of the cases, 11 out of 222 patients, mostly caused by hematotoxicity. Conclusion FAP-RLT has demonstrated significant disease control in multiple advanced solid tumours while maintaining a favourable safety profile. These findings can contribute to clinical treatment expectations and support informed policy decision-making in oncology.
Zhang et al. (Wed,) studied this question.