Safety of selinexor as the only exportin 1 (XPO1) inhibitor so far: a post-marketing study based on the world Health Organization pharmacovigilance database (Vigibase)

ABSTRACTBackground Exportin 1 (XPO1) inhibitors are being developed as a new agent for anti-cancer therapies. This study aimed to broadly portray the adverse event (AE) profile of selinexor, an XPO1 inhibitor, in actual clinical practice.Research design and methods Disproportionality analyses were conducted by calculating the information component and reporting odds ratio in VigiBase over different reporting periods. All selinexor-related AEs were classified by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities.Results A total of 116,443 AEs were identified in 2,608 patients that received selinexor. Patients with cardiac disorders had a higher propensity for death. Thirteen SOCs and 125 PTs were identified as having a potential connection with selinexor. Notably, 29 suspected signals detected in our study were defined as significant AEs by the European Medicines Agency, including febrile neutropenia, pancytopenia, and acute kidney injury. Attention should be paid to these AEs, despite most toxicities being manageable and reversible.Conclusions This study highlights a number of AEs associated with selinexor. Most toxicities are reversible but require careful management. The benefit of selinexor still outweighs the potential risks, indicating XPO1 inhibitors as promising agents.KEYWORDS: Disproportionality analysispharmacovigilanceselinexorSINEVigiBaseXPO1 Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contribution statementC Chen and X Guo conceptualized and designed the study, carried out the initial analysis, drafted the initial manuscript, and reviewed and revised the manuscript. X Miao reviewed and revised the manuscript from the perspective of clinical practice, conceptualized and designed the study, improved the language and clarity of the article. J Xu designed the data collection instruments, supervised data collection, Y Zheng, L Chi and X Chen checked all the data analysis and reviewed and revised the manuscript. J Liang, H Zhang and L Wei collected data, coordinated the initial data analysis, and reviewed and revised the manuscript. X Ye, and J He conceptualized and designed the study, coordinated, and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.AcknowledgmentsThe data provided by VigiBase come from a variety of sources. In all reports, the likelihood of causality is different. This information does not represent the opinion of the WHO. At the same time, the authors would like to thank the research department of Uppsala Monitoring Center (Uppsala, Sweden) for their help in data extraction.Data availability statementData is available on request from the Uppsala Monitoring Centre of the WHO Program for International Drug Monitoring (https://www.who-umc.org/vigibase/vigibase/).Additional informationFundingThis paper was funded by the National Nature Science Foundation of China (No. 82073671), the Big Data and Artificial Intelligence Application and the Military Key Discipline Construction Project (Health Service Naval Health Service Organization and Command, No. 03).