Adverse Events Associated With Dabrafenib, Trametinib, and Their Combination Therapy: A Disproportionality Analysis of the FDA Adverse Event Reporting System (FAERS) Database.

Abstract

Objective: Based on the FAERS database, this study aims to compare the safety of dabrafenib, trametinib, and their combination therapy, providing a reference for clinically safe medication.

Methods: Adverse event data for dabrafenib, trametinib, and their combination were extracted from the FAERS database. Descriptive statistical analysis was performed, and adverse event signals were mined using the Reporting Odds Ratio (ROR) method and the Bayesian Confidence Propagation Neural Network (BCPNN) method.

Results: The dabrafenib group yielded 11 048 adverse event reports with 311 positive signals across 22 organ systems. The trametinib group had 7848 reports with 249 positive signals across 21 organ systems. The combination therapy group had 13 544 reports with 418 positive signals across 23 organ systems. Signals were primarily concentrated in investigations, while adverse event reports mainly focused on general disorders and administration site conditions. The distribution of adverse events within System Organ Classes (SOCs) differed among the three groups.

Conclusion: Dabrafenib was associated with stronger reporting signals for adverse events such as fever, hyperpyrexia, and tumor progression. Trametinib was associated with skin-related or infectious adverse events like rash, acneiform dermatitis, and paronychia. The combination therapy increased the risk of ocular and cardiovascular adverse events. These signals indicate potential risks but require clinical confirmation. Clinical practice should prioritize monitoring different adverse events based on patient characteristics and drug type.