Abstract
Lapatinib is a clinically important component of the treatment for HER2-positive metastatic breast cancer and has an acceptable safety profile. Lapatinib-associated Hy's Law cases have been characterized using human leukocyte antigen (HLA) DQA1*02:01/DRB1*07:01 and Gilbert's syndrome UGT1A1*28/*28 genotypes. The HLA-positive cases had higher alanine aminotransferase (ALT) elevation, whereas the HLA-negative cases had a higher incidence of Gilbert's syndrome. The findings of our study, which extend this HLA association to lapatinib-associated serious liver injury, emphasize the importance of Gilbert's syndrome in the interpretation of Hy's Law and may lead to methods for enhancing patient safety.
Publication types
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Clinical Trial
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Comparative Study
MeSH terms
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Alanine Transaminase / biosynthesis
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Alanine Transaminase / genetics
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Chemical and Drug Induced Liver Injury / epidemiology
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Chemical and Drug Induced Liver Injury / genetics*
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Chemical and Drug Induced Liver Injury / immunology
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Genotype
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Gilbert Disease / drug therapy
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Gilbert Disease / genetics*
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Gilbert Disease / immunology
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Glucuronosyltransferase / biosynthesis
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Glucuronosyltransferase / genetics*
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HLA-DQ alpha-Chains / biosynthesis
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HLA-DQ alpha-Chains / genetics*
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HLA-DRB1 Chains / biosynthesis
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HLA-DRB1 Chains / genetics*
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Humans
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Incidence
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Lapatinib
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Quinazolines / adverse effects*
Substances
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HLA-DQ alpha-Chains
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HLA-DQA1 antigen
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HLA-DRB1 Chains
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HLA-DRB1*07:01:01 antigen
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Quinazolines
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Lapatinib
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UGT1A1 enzyme
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Glucuronosyltransferase
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Alanine Transaminase