Title : Analysis of adverse events of anaplastic lymphoma kinase inhibitors reported to FDA adverse event reporting system (FAERS)
Abstract:
Targeted cancer therapy often causes fewer adverse effects than traditional chemotherapy drugs. Thus, targeted therapeutic drugs have become mainstream of several hematologic and solid malignancies including non-small cell lung cancer (NSCLC). The first anaplastic lymphoma kinase (ALK) inhibitor, crizotinib was approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of NSCLC with alteration of ALK gene. Three more ALK inhibitors i.e., ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved to enter the market. Since 2011, 19,298 adverse event cases associated with ALK inhibitors have been reported to FAERS (data as of September 30, 2022). 14,176 of those cases were serious cases (including deaths). The aim of this study was to explore the characteristics of adverse events associated with the ALK inhibitors. To establish an association between ALK inhibitors and adverse events, patient cases with polypharmacy were excluded, which brought the total number of cases down to 16,868 for analysis. Adverse reactions describing the adverse events in each individual case were mapped to system organ class (SOC) based on Medical Dictionary for Regulatory Activities (MedDRA) system. Of those 16,868 cases, total number of patients with at least one adverse event were on crizotinib (N=9,036), alectinib (N=3913), ceritinib (N=2183) and Brigatinib (N=1736). Common SOCs associated with ALK inhibitors were “General disorders and administration site conditions”, “Gastrointestinal disorders”, “Respiratory, thoracic and mediastinal disorders”, “Neoplasms benign, malignant and unspecified (incl cysts and polyps)”, “Nervous system disorders”, “Investigations”, “Cardiac disorders”, “Injury, poisoning and procedural complications”, “Vascular disorders”, “Musculoskeletal and connective tissue disorders”, and “Skin and subcutaneous tissue disorders”. Since cardiac toxicities are often a major concern clinically, a breakdown of cardiac adverse reactions such as bradycardia, atrial fibrillation, pericardial effusion, dyspnoea, and cardiac arrest was further characterized.
Audience Take Away Notes:
- The audience will be able learn and discuss real-world adverse event characteristics of ALK inhibitors.
- The presentation will bring awareness to patients/prescribers/researchers about the organ systems that are commonly affected by the adverse effects of ALK inhibitors.
- With the different adverse event characteristic profile among the four ALK inhibitors available in the market, the information presented could help the patients/prescribers as part of their informed decision-making to choose the most appropriate drug.
- Other researchers could use this presentation to generate a research hypothesis or expand their own research work.
