Osimertinib induced cardio-toxicity: A retrospective review of FDA adverse events reporting system (FAERS).

Abstract

9044 Background: Osimertinib is an oral third generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). In the FLAURA trial (a Phase III randomized-control trial) Osimertinib arm had higher rate of cardio-toxicity compared to standard EGFR-TKIs. We queried FAERS database to find out rate of cardio-toxicity caused by Osimertinib compared to other EGFR-TKIs. Methods: We queried FAERS for “Cardiac failure”, “Electrogram QT-prolonged”, “Atrial Fibrillation(A.fib)”, “Myocardial Infarction(MI)”, “Cardiac failure congestive(CFC)” and “Pericardial Effusion(PE)” secondary to “Osimetinib”, “Erlotonib”, “Afatinib” and “Gefitinib” from 2016-2018. Disproportionality signal analysis was done by calculating Reporting Odds Ratio (ROR) with 95% confidence interval (CI). ROR was considered significant when lower limit of 95% CI was > 1. Results: Total AEs from all drugs were 5,138,230. Total AEs from all 4 TKIs were 8450, 2454 due to Osimertinib, 5836 due to other TKIs and 160 due to combination of both Osimertinib plus any of other 3 TKIs. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC due to Osimertinib was 6.4(4.7-8.7), 4(2.8-5.8), 11.2(7.9-15.8), 1.6(0.9-2.6), 8.2(4.8-14) and 3.9(2.4-6.3) respectively. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC on comparing Osimertinib vs other TKIs was 2.1(1.3-3.2), 2.1(1.3-3.5), 6.6(3.4-12.8), 1.2(0.6-2.3), 1.6(0.8-3.3) and 2.3(1.2-4.6) respectively. Findings are summarized in Table. Conclusions: Rate of QT prolongation, cardiac failure, CFC and A.fib were found to be higher due to Osimertinib compared to other TKIs. EKG monitoring for QT prolongation and monitoring for signs/symptoms of heart failure should be considered while using Osimertinib. [Table: see text]