Impact of Proton Pump Inhibitors on Osimertinib-Induced Cardiotoxicity in NSCLC Patients

Abstract

There is a lack of comprehensive research investigating the relationship between proton pump inhibitors (PPIs) and osimertinib combination therapy concerning cardiotoxicity. We conducted a retrospective analysis of adverse event reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS). In this analysis, we used patients with non-small cell lung cancer (NSCLC) who did not receive osimertinib or PPIs as a control group to assess the association between cardiotoxicity occurrence in patients receiving osimertinib with PPIs and those without PPIs. We employed disproportionality analysis along with both additive and multiplicative models. The reporting odds ratios (ROR) for cardiac events, including torsade de pointes/QT prolongation, cardiomyopathy, cardiac arrhythmias, cardiac failure, ischaemic heart disease, and embolic and thrombotic events, were significantly higher in patients using PPIs with osimertinib (14.11, 9.04–22.04; 4.67, 2.67–8.16; 4.43, 3.17–6.20; 3.67, 2.53–5.34; 2.24, 1.31–3.84; 1.92, 1.43–2.56, respectively) compared to osimertinib alone (4.87, 3.91–6.07; 2.50, 2.02–3.09; 1.59, 1.37–1.84; 2.00, 1.74–2.29; 0.65, 0.50–0.84; 1.01, 0.91–1.11). Our investigation unveiled an elevated risk of cardiotoxicity in NSCLC patients when osimertinib was combined with PPIs, compared to osimertinib monotherapy. Therefore, vigilant monitoring for cardiotoxicity is paramount in NSCLC patients undergoing these combined treatments.