Aplastic anemia associated with osimertinib: Analysis of the FDA adverse event reporting system

Objective: Aplastic anemia (AA) is a life-threatening disease, and druginduced AA is rare. Recently, studies on cases that possibly developed AA following osimertinib treatment have been conducted. This study evaluated the association of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including osimertinib, with AA and characterized such registered patients using a large spontaneous adverse event reporting database. Materials and methods: Data from the Food and DrugAdministration'sAdverse Event Reporting System spanning from the first quarter of 2015 to the second quarter of 2023 were used. Disproportionality analyses with reporting odds ratio (ROR) and information component (IC) were performed for signal detection. Furthermore, we described a case series of patients who experienced AA during osimertinib treatment. Results: A signal was detected with osimertinib (ROR: 4.16, 95% confidence interval (CI): 2.54 - 6.80; IC: 1.80, 95% CI: 1.10 - 2.51); however, no signals were detected with other EGFR-TKIs. 16 individuals treated with osimertinib had AA, of whom 14 (87.5%) were registered as suspected drugs. The median age of these individuals was 70.5 years (interquartile range (IQR), 64.8 - 78.3 years), with varying time to onset (IQR, 4 - 210 days) and outcomes, including 3 (18.8%) deaths. Conclusion: Our analyses generated a safety signal for the as sociation between osimertinib and AA. Further studies are required to understand and confirm the role of osimertinib administration in the development of AA.