A Real-World Pharmacovigilance Analysis of Lorlatinib-Associated Metabolic Effects Using the FDA Adverse Events Reporting System (FAERS) Database From 2013 to 2024.

Objective: The advent of anaplastic lymphoma kinase (ALK) inhibitors, including lorlatinib, has transformed the treatment of ALK-rearranged malignancies. While lorlatinib effectively overcomes resistance mutations and penetrates the central nervous system, its use is associated with metabolic adverse events, including hypercholesterolemia, hypertriglyceridemia, and weight gain. These complications increase cardiovascular risks, disrupt metabolic homeostasis, and may affect therapy adherence.

Methods: This study utilizes data from the FDA Adverse Event Reporting System and employs disproportionality analysis to investigate the prevalence and nature of lorlatinib-associated metabolic adverse events.

Results: Significant associations were identified between lorlatinib and lipid-related adverse events, including hypercholesterolemia (reporting odds ratio [ROR] = 98.46; 95% CI: 79.28-122.29), hypertriglyceridemia (ROR = 66.10; 95% CI: 49.60-88.11), increased body mass index (ROR = 81.57; 95% CI: 48.87-136.14), and increased blood cholesterol (ROR = 23.42; 95% CI: 19.69-27.86). Additional associations were noted for increased blood triglycerides (ROR = 28.14; 95% CI: 22.15-35.75) and dyslipidemia (ROR = 53.60; 95% CI: 38.51-74.60).

Conclusion: These findings highlight the need for proactive monitoring and management of metabolic side effects in patients receiving lorlatinib. A multidisciplinary approach-incorporating pharmacologic interventions, lifestyle modifications, and regular monitoring-is essential to mitigate metabolic risks. This study enhances the understanding of lorlatinib's safety profile and informs clinical strategies to balance efficacy and tolerability in ALK inhibitor therapy.