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A Real-World Pharmacovigilance Analysis of Lorlatinib-Associated Metabolic Effects Using the FDA Adverse Events

Connor Frey1

  • 1Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
|April 26, 2025
PubMed
Abstract

Insights

Lorlatinib, an anaplastic lymphoma kinase (ALK) inhibitor, is linked to significant metabolic adverse events like hypercholesterolemia and weight gain. Proactive monitoring and management are crucial for patients receiving this therapy.

Area of Science:

  • Oncology
  • Pharmacovigilance
  • Metabolic Medicine

Background:

  • Anaplastic lymphoma kinase (ALK) inhibitors, including lorlatinib, have revolutionized ALK-rearranged cancer treatment.
  • Lorlatinib demonstrates efficacy in overcoming resistance and CNS penetration but is associated with metabolic adverse events.
  • These events, such as hypercholesterolemia, hypertriglyceridemia, and weight gain, pose risks to cardiovascular health and treatment adherence.

Purpose of the Study:

  • To investigate the prevalence and characteristics of metabolic adverse events associated with lorlatinib.
  • To analyze the safety profile of lorlatinib concerning metabolic disturbances.

Main Methods:

  • Utilized data from the FDA Adverse Event Reporting System (FAERS).
  • Employed disproportionality analysis, specifically reporting odds ratios (ROR) with 95% confidence intervals (CI), to assess adverse event associations.

Main Results:

  • Identified significant associations between lorlatinib and hypercholesterolemia (ROR = 98.46), hypertriglyceridemia (ROR = 66.10), and increased body mass index (ROR = 81.57).
  • Further associations noted for increased blood cholesterol (ROR = 23.42), increased blood triglycerides (ROR = 28.14), and dyslipidemia (ROR = 53.60).

Conclusions:

  • Lorlatinib is significantly associated with a range of metabolic and lipid-related adverse events.
  • Emphasizes the critical need for proactive monitoring and management of these side effects in clinical practice.
  • A multidisciplinary approach is essential to mitigate risks and optimize patient outcomes while maintaining therapeutic efficacy.
Keywords:
ALKanaplastic lymphoma kinasedyslipidemialorlatinibmetabolic syndromeweight Gain

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