Safety evaluation of selective estrogen receptor degraders (SERDs) using real-world evidence from the FDA Adverse Event Reporting System (FAERS)

This study aims to evaluate post-marketing adverse event data for two selective estrogen receptor degraders (SERDs) in a real-world context, identify potential risk signals, and offer insights for clinical pharmacovigilance. Data were extracted from the U.S. FDA Adverse Event Reporting System (FAERS) database, covering the period from Q1 2004 to Q4 2024. The analysis commenced with elacestrant (2022) and fulvestrant (2004), concluding in the fourth quarter of 2024. Data standardization was achieved using MedDRA version 27.0. Signal detection employed four methodologies: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). A total of 6,636 adverse event (AE) reports identified elacestrant as the primary suspected drug, while 9,120 reports identified fulvestrant as the primary suspected drug. Both drugs commonly induced adverse reactions such as nausea, vomiting, disease progression, elevated liver enzymes, and hot flashes. Elacestrant was frequently associated with abnormal tumor markers and esophageal-related reactions. In contrast, fulvestrant was linked to a higher incidence of tumor metastasis and may also affect the hematological and lymphatic systems, as well as the cardiovascular and respiratory systems. Both classes of SERDs demonstrated a generally favorable overall safety profile, although differences were noted in their specific adverse reaction profiles. For elacestrant, particular attention should be given to dehydration, abnormal tumor markers, and esophageal-related reactions. For fulvestrant, increased vigilance is necessary regarding cancer metastasis and adverse events impacting the hematological and lymphatic systems. It is recommended that targeted monitoring be enhanced in clinical practice in accordance with the distinct characteristics of each drug.