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

Abstract

Background: Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are highly effective treatments for ALKpositive 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 (

Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study

“…We noted that a more extensive FAERS study of ALK-TKIs ( Omar et al, 2021 ) was recently published where the authors analyzed all AEs of ALK-TKIs primarily at the SOC, but they did not report any cardiac AEs. The reason might be that the data mining methods we used were different.…”

Psychiatric Adverse Reactions to Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer: Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System

“…In recent years, the development of ALK inhibitors has improved the survival outcomes of advanced ALK-rearranged NSCLC patients. In addition, the AEs with ALK TKIs are fairly well known, although emerging data are starting to accrue from pharmacovigilance [ 17 ]. Spontaneous reporting systems are needed to identify and better characterize the different AEs in a timely manner in the real world, thus increasing awareness by oncologists to handle them promptly.…”

Alectinib-associated pneumoperitoneum in stage IV non-small cell lung cancer - A case report

“…It is the first line treatment for advanced ALK-positive NSCLC in adults with several clinical trials demonstrating less CNS disease progression as well as longer progression-free survival as well as lower rates of adverse events than crizotinib, the first tyrosine kinase inhibitor to be approved for ALK-positive advanced NSCLC [ 8 ]. Of these adverse events, hepatobiliary disorders and photosensitivity are the most commonly associated with alectinib [ 6 ].…”

“…It is a highly potent, central nervous system penetrant ALK inhibitor with a relatively low side effect profile. The most common side effects of alectinib therapy are photosensitivity, myalgias, and hepatobiliary disorders; with very few gastrointestinal (GI) complaints reported [ 6 ]. In compliance with the 2020 SCARE guidelines, we present a rare case of a 74-year-old female diagnosed with NSCLC who was initiated on alectinib therapy and subsequently developed pneumoperitoneum [ 7 ].…”