Abstract
Objective Lorlatinib,as a third-generation anaplastic lymphoma kinase(ALK)inhibitor,demonstrates sig-nificant antitumor activity;however,its long-term safety profile and adverse events warrant further investigation and analy-sis.Methods Based on the U.S.FDA Adverse Event Reporting System(FAERS)and the Japanese Adverse Drug Event Re-porting System(JADER),adverse event reports related to lorlatinib between 2018 and 2024 were retrieved and extracted.The reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods were employed for statistical analysis and signal mining of the reported data.Results At the preferred term(PT)level,in the FAERS database,the strongest signals were ranked as follows:mean arterial pressure increased(ROR=311,PRR=310.89),very low density lipoprotein increased(ROR=239.35,PRR=239.15),brain radiation necrosis(ROR=233.23,PRR=233.17),body surface area increased(ROR=197.13,PRR=197),and lipid abnormality(ROR=142.79,PRR=142.57).In the JADER database,the strongest signals were:hypercholesterolaemia(ROR=1 755.18,PRR=1 699.4),affective disorder(ROR=397.45,PRR=394.73),hyperlipidaemia(ROR=330.68,PRR=323.7),blood cholesterol increased(ROR=271.98,PRR=266.57),and low density lipoprotein increased(ROR=156.86,PRR=155.5).At the system organ class(SOC)level,in the FAERS database,significant signals were identified for investigations(ROR=2.64,PRR=2.41)and metabolism and nutrition disorders(ROR=2.41,PRR=2.34).In the JADER da-tabase,significant signals were identified for psychiatric disorders(ROR=10.05,PRR=8.73),benign,malignant and unspeci-fied neoplasms(including cysts and polyps)(ROR=2.77,PRR=2.54),and metabolism and nutrition disorders(ROR=2.62,PRR=2.45).Time-to-onset analysis revealed that in both the FAERS and JADER databases,60.08％and 78.88％of lorlati-nib-related adverse events occurred within the first two months of treatment,respectively.Conclusion The signal mining re-sults based on the two databases suggest that adverse events already documented in the drug label,such as interstitial lung dis-ease(ILD)and atrioventricular block,warrant continued monitoring and evaluation.At the same time,increased attention should be given to newly identified potential adverse events,including pulmonary hypertension and radiation necrosis.关键词
洛拉替尼/FAERS数据库/JADER数据库/药品不良事件/报告比值比/比例报告比值比Key words
Lorlatinib/FAERS database/JADER database/Adverse drug events/Reporting odds ratio/Proportional re-porting ratio分类
医药卫生
