Table2_Post-marketing safety of lorlatinib: a real-world study based on the FDA adverse event reporting system.XLSX

BackgroundLorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish the safety profile of lorlatinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsReports from the FAERS between 2019 and 2023 were collected to conduct the disproportionality analysis. Reporting odds ratio (ROR) was employed to detect the potential adverse events (AEs) related to lorlatinib. The clinical characteristics, age and gender differences, time to onset of AEs were also investigated.ResultsA total of 2,941 AE reports were found to be associated with lorlatinib among the 8,818,870 AE reports obtained from the FAERS database. 167 lorlatinib-related AE signals were identified. The frequently reported AEs including hypercholesterolemia, oedema, and cognitive disorder were in line with those observed in clinical trials and drug instruction. However, AEs such as interstitial lung disease and AV block indicated in the drug label require further evaluation. More attention should be paid to the new potential unexpected AEs including pulmonary arterial hypertension and radiation necrosis. Furthermore, we examined the specific high-risk AEs of different ages and genders. In addition, majority of AEs occurred within the first 2 months after lorlatinib initiation with a median onset time of 51 days.ConclusionOur study provides valuable insight into the post-marketing safety profile of lorlatinib, which can potentially benefit the rational and safe administration of lorlatinib in the clinic. Further prospective studies are needed to validate the associations between lorlatinib and the identified AEs.

背景：Lorlatinib在系统性及颅内治疗间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）方面表现出显著疗效。本研究旨在基于食品药品监督管理局不良事件报告系统（FAERS）建立lorlatinib的安全性档案。方法：收集了2019年至2023年FAERS报告，进行不均衡性分析。采用报告比值比（ROR）检测lorlatinib相关的潜在不良事件（AEs）。同时，调查了AEs的临床特征、年龄和性别差异以及AEs的发作时间。结果：在从FAERS数据库获得的8,818,870份AE报告中，共发现2,941份与lorlatinib相关的AE报告。确定了167个lorlatinib相关的AE信号。频繁报告的不良事件，包括高胆固醇血症、水肿和认知障碍，与临床试验和药物说明中观察到的结果一致。然而，药物标签中提及的间质性肺病和房室传导阻滞等AE需要进一步评估。应更加关注包括肺动脉高压和辐射坏死在内的新潜在非预期AEs。此外，我们还考察了不同年龄和性别的高风险AEs。大多数AEs在lorlatinib起始后的前2个月内发生，中位发作时间为51天。结论：本研究为lorlatinib上市后的安全性档案提供了宝贵见解，这有助于lorlatinib在临床上的合理和安全使用。需要进一步的前瞻性研究来验证lorlatinib与所识别的AEs之间的关联。