Cardiac safety profile of type II kinase inhibitors: Analysis of post-marketing reports from databases of European Medicine Agency & World Health Organization.

Background: Targeted therapy with type II kinase inhibitors (KIs) is one of the preferred choices in cancer treatment. However, type II KI therapy can be associated to serious cardiac risks.

Objectives: This study aimed to assess the occurrence of cardiac events reported with type II KIs in Eudravigilance (EV) and VigiAccess databases.

Methods: To evaluate reporting frequency of individual case safety reports (ICSRs) related to cardiac events, we referred EV and VigiAccess databases. The data was retrieved for the period from date of marketing authorization of respective type II KI till 30 July 2022. Computational analysis was conducted with data from EV and VigiAccess using reporting odds ratio (ROR) along with its 95% confidence interval (CI) under Microsoft excel.

Results: In total, 14429 ICSRs in EV and 11522 ICSRs from VigiAccess were retrieved concerning cardiac events with at least one type II KI as the suspected drug. In both databases, most of the ICSRs were reported for Imatinib, Nilotinib, and Sunitinib, while most reported cardiac events were myocardial infarction/acute myocardial infarction, cardiac failure/congestive heart failure and atrial fibrillation. As per EV, 98.8% ICSRs with cardiac ADRs were assessed as serious and of which, 17.4% ICSRs were associated with fatal outcomes and approximately 47% included patient's recovery as a favorable outcome. Nilotinib (ROR 2.87, 95% CI 3.01-2.74) and Nintedanib (ROR 2.17, 95% CI 2.3-2.04) were associated with a significant increase in reporting frequency of ICSRs related to cardiac events.

Conclusions: Type II KI related cardiac events were serious and associated with unfavorable outcomes. A significant increase in ICSRs reporting frequency was observed with Nilotinib and Nintedanib. These results insist for a consideration of revision of cardiac safety profile of Nilotinib and Nintedanib, specifically for risks of myocardial infarction and atrial fibrillation. Additionally, the need for other ad-hoc studies is indicated.