PII-189 - EVALUATION OF CARDIOVASCULAR TOXICITY PROFILE OF ALK INHIBITORS USING ADVERSE EVENT REPORTING DATABASE

T. Niimura¹, K. Miyata², K. Yagi¹, F. Aizawa¹, K. Kawada¹, M. Goda¹, Y. Izawa-Ishizawa¹, K. Ishizawa¹; ¹Tokushima University, ²Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences.

Background: In recent years, cases of cardiovascular toxicity, including pericarditis, have been reported with anaplastic lymphoma kinase (ALK) inhibitors, but it is not yet clear how the profile of cardiovascular toxicity differs among the multiple ALK inhibitors on the market. The purpose of this study was to determine the cardiovascular toxicity profile of ALK inhibitors using the adverse event spontaneous reporting database.

Methods: Data from VigiBase, the WHO adverse event reporting database, from 1968 to the time of publication in December 2021 were analyzed. Reported odds ratios were calculated to evaluate the association of ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) with various cardiovascular adverse events. A safety signal was considered detected if the lower limit of the 95% confidence interval for the reported odds ratio was greater than 1. The time from ALK inhibitor administration to the onset of pericarditis was also analyzed for each ALK inhibitor. VigiBase datebase is an anonymized patient information, institutional review board approval and informed consent were not required.

Results: Of the 27,994,584 adverse event reports, 19,911 were related to ALK inhibitors. Among the cardiovascular toxicities studied, safety signals for pericarditis were detected in all five ALK inhibitors; for torsade de pointes/QT prolongation, in crizotinib and ceritinib; for hypertension, in brigatinib; and for heart failure, in alectinib, crizotinib and lorlatinib. signals were detected. Analysis of the time from drug administration to the onset of pericarditis showed a difference in duration between drugs, ranging from 52.5 days for alectinib to 166.5 days for crizotinib.

Conclusion: Systematic evaluation of cardiovascular toxicity associated with ALK inhibitors has revealed differences in cardiovascular toxicity profiles among ALK inhibitors. Understanding the differences in cardiovascular toxicity profiles of each ALK inhibitor is expected to contribute to safe cancer drug therapy.