Postmarketing safety of [177Lu]Lu-PSMA-617 radioligand therapy for prostate cancer: a disproportionality analysis of the FDA adverse event reporting system

Background [Lu-177]Lu-PSMA-617 (Pluvicto), a new radioligand therapy that targets prostate-specific membrane antigen (PSMA), has been approved to treat metastatic castration-resistant prostate cancer (mCRPC). However, the real-world safety profile of [Lu-177]Lu-PSMA-617 has not been systemically evaluated. Research design and methods Adverse event reports for [Lu-177]Lu-PSMA-617 were retrieved from April 2022 to June 2024 from The Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted by four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Multi-Item Gamma Poisson Shrinker (MGPS) and Bayesian Confidence Propagation Neural Network (BCPNN). Subgroup analysis, time-to-onset and sensitivity analysis were also employed. Results 384,2712 adverse event reports were retrieved, of which 870 were associated with [Lu-177]Lu-PSMA-617 in prostate cancer patients. We identified known adverse events (fatigue/asthenia, anemia, thrombocytopenia and nausea) and discovered adverse events not specified on the label (loss of libido, hydronephrosis, supraventricular tachycardia, tumor lysis syndrome, and tumor flare). Subgroup analysis revealed high-risk signals included stomatitis, pneumonia, leukopenia, and sepsis for patients aged over 85. The median onset time was 55 days (interquartile range 24-124 days). Conclusions The findings provide new insights into the adverse events of [Lu-177]Lu-PSMA-617 and valuable references for clinical applications of radioligand therapy for mCRPC.