Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)

ESMO Open

article

N.E. Omar¹  A.I. Fahmy Soliman²  M. Eshra²  T. Saeed³  A. Hamad¹  A. Abou-Ali⁴ 

[1] Pharmacy Department, National Center for Cancer Care and Research;Faculty of Pharmacy, Alexandria University;Faculty of Computer Sciences and Information Technology, Cairo University;Astellas Pharma

关键词: ALK inhibitors;    pharmacovigilance;    adverse events;    post-marketing surveillance;    pharmacoepidemiology;    lung cancer;   

DOI  :  10.1016/j.esmoop.2021.100315

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are highly effective treatments for ALK-positive lung cancer. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS).Patients and methods FAERS files from 2012 to 2020 were used. Reports for crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib were filtered. We used the Medical Dictionary for Regulatory Activities (MedDRA version 22.1). Further, we searched for adverse events on the preferred term (PT) level based on case reports in the literature. After filtering duplicate reports, disproportionality analysis was used to detect safety signals by calculating proportional reporting ratios (PRRs), reporting odds ratios (RORs), empirical Bayesian geometric mean, and information component. Reports were considered statistically significant if the 95% confidence interval did not contain the null value.Results Within the system organ classes, significant safety signals were found, including those for crizotinib [eye disorders (PRR 2.09, ROR 2.12)], ceritinib [gastrointestinal disorders (PRR 2.19, ROR 2.41), hepatobiliary disorders (PRR 4.4, ROR 4.52), respiratory disorders (PRR 1.96, ROR 2.08)], alectinib [hepatobiliary disorders (PRR 2.60, ROR 2.63)], brigatinib [respiratory disorders (PRR 2.15, ROR 2.31)], and lorlatinib [metabolism disorders (PRR 3.34, ROR 3.53)]. For adverse events on the PT level, we found several significant signals, including pneumothorax with crizotinib (PRR 3.29, ROR 3.29), ceritinib (PRR 3.13, ROR 3.13), and alectinib (PRR 4.88, ROR 4.89); myasthenia gravis with lorlatinib (PRR 6.05, ROR 6.05); photosensitivity reactions with crizotinib (PRR 2.20, ROR 2.20), ceritinib (PRR 4.30, ROR 4.31), alectinib (PRR 20.43, ROR 20.51), and brigatinib (PRR 20.97, ROR 21.05); pulmonary arterial hypertension with brigatinib (PRR 2.92, ROR 2.92) and lorlatinib (PRR 9.2, ROR 9.24); and rectal perforation with crizotinib (PRR 7.83, ROR 7.83). All the detected safety signals were confirmed using Bayesian methods.Conclusion ALK inhibitors differed in their safety profile reports. We found several significant safety signals that matched previously published case reports, including pulmonary arterial hypertension, rectal perforation, myasthenia gravis, and photosensitivity. These signals require further regulatory investigation to determine their significance and potentially update the product labels to inform patients and clinicians.

【 授权许可】

CC BY|CC BY-NC-ND