Postmarketing safety of [177Lu]Lu-PSMA-617 radioligand therapy for prostate cancer: a disproportionality analysis of the FDA adverse event reporting system.
This study highlights the importance of monitoring adverse events associated with [177Lu]Lu-PSMA-617, particularly in older patients who may be at higher risk.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study analyzed adverse event reports associated with [177Lu]Lu-PSMA-617 in prostate cancer patients. A total of 870 adverse events were identified from 384,2712 reports, with known and novel adverse events documented. The median onset time for these events was 55 days.
Abstract
Background [177Lu]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 [177Lu]Lu-PSMA-617 has not been systemically evaluated. Research design and methods Adverse event reports for [177Lu]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 [177Lu]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 [177Lu]Lu-PSMA-617 and valuable references for clinical applications of radioligand therapy for mCRPC.
Background
This paper addresses the safety profile of [177Lu]Lu-PSMA-617, a radioligand therapy approved for metastatic castration-resistant prostate cancer (mCRPC). Prior to this study, the real-world safety of this treatment had not been systematically evaluated, making this analysis significant for understanding potential risks associated with its use.
Methods
Adverse event reports were retrieved from the FDA Adverse Event Reporting System (FAERS) database from April 2022 to June 2024. A total of 384,2712 reports were analyzed, with 870 specifically associated with [177Lu]Lu-PSMA-617. Disproportionality analysis was conducted using four algorithms, and subgroup analyses were performed.
Results
870 adverse events were identified in patients treated with [177Lu]Lu-PSMA-617. Known adverse events included fatigue/asthenia, anemia, thrombocytopenia, and nausea, while novel events included loss of libido and tumor lysis syndrome. The median onset time for adverse events was 55 days (interquartile range 24-124 days).
Interpretation
The findings indicate both known and novel adverse events associated with [177Lu]Lu-PSMA-617, contributing to the understanding of its safety profile. While the statistical significance of the findings is noted, the clinical significance may vary, particularly in older patients. The reliance on adverse event reporting introduces potential confounds such as underreporting or bias.
Key findings
- 870 adverse event reports associated with [177Lu]Lu-PSMA-617 in prostate cancer patients.
- Median onset time was 55 days (interquartile range 24-124 days).
- High-risk signals included stomatitis, pneumonia, leukopenia, and sepsis for patients aged over 85.
Limitations
- Relies on adverse event reporting, which may be subject to underreporting.
- Analysis based on data from the FAERS database, which may not represent the entire patient population.
- Potential bias in reporting may affect the findings.