5PSQ-060 Leveraging the WHO pharmacovigilance database vigiBase: example of the safety analysis of (¹⁷⁷Lu)Lu-DOTATATE

<h3>Background and Importance</h3> Radioligand therapy, a therapeutic application of the radiotheranostic concept, is based on the use of a therapeutic radiopharmaceutical that targets a biomarker of interest in a given pathology. One example is (¹⁷⁷Lu)Lu-DOTATATE, used in the treatment of metastatic or inoperable, well-differentiated gastroenteropancreatic neuroendocrine tumours expressing somatostatin receptors. Clinical trials used to determine the safety of the drug do not represent a ‘real-life’ population. In order to provide a comprehensive safety analysis, we have used the World Health Organization’s pharmacovigilance database, VigiBase. <h3>Aim and Objectives</h3> This study aims to elucidate a comprehensive safety profile with real-life data of a therapeutic radiopharmaceutical such as (¹⁷⁷Lu)Lu-DOTATATE using VigiBase. <h3>Material and Methods</h3> An extraction of individual safety reports (ICSRs) reported and associated with (¹⁷⁷Lu)Lu-DOTATATE was performed. The general characteristics of the ICSRs were recorded. Adverse drug reactions (ADR) reporter in the ICSRs were sorted to create an ADR dictionary divided into classes and subclasses. A retrospective disproportionality analysis of ICSRs was then performed using the information component (IC, at alpha risk 0.05: IC₀₂₅). The different classes of ADR were described, including the identification of overlaps between classes and the time taken for ADR to appear after initiation of the radiopharmaceutical. <h3>Results</h3> A total of 3,984 ICSRs related to (¹⁷⁷Lu)Lu-DOTATATE were analysed, with the majority of reports originating from the Americas (65%) and reported by physicians (45%). The most commonly co-reported drugs were octreotide (6%), amino acids (6%), ondansetron (6%), and lanreotide (5%). Disproportionality analysis identified significant associations between (¹⁷⁷Lu)Lu-DOTATATE and several ADR classes, including haematologic malignancies (IC₀₂₅=2.48), haematologic disorders (IC₀₂₅=2.15), liver disorders (IC₀₂₅=1.43), renal failure (IC₀₂₅=1.16), infections (IC₀₂₅=0.91), alopecia (IC₀₂₅=0.74), and metabolic disorders (IC₀₂₅=0.17). The overlaps between classes were identified, including an overlap between haematological disorders and infections. The median time to onset of ADRs was also calculated and the longest delay was observed for haematologic malignancies. <h3>Conclusion and Relevance</h3> The VigiBase pharmacovigilance database, offers essential insights into the safety profile of (¹⁷⁷Lu)Lu-DOTATATE and can be leveraged for the evaluation of the safety of other therapeutic radiopharmaceuticals. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest