Safety evaluation of selective RET inhibitors in patients with lung cancer: a real-world pharmacovigilance study

Selpercatinib and pralsetinib are targeted therapies for non-small cell lung cancer. However, their adverse reaction profiles remain incompletely understood. This study aims to evaluate the post-marketing adverse events (AEs) associated with selpercatinib and pralsetinib in real-world populations.

We conducted a comprehensive analysis of AEs linked to selective RET inhibitors using advanced data mining techniques on the FDA Adverse Event Reporting System. Disproportionality analysis was performed to quantify the association between these drugs and AEs. Key metrics for disproportionality assessment included the reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayesian geometric mean.

A total of 522 and 917 AE reports were identified for selpercatinib and pralsetinib in lung cancer patients, with 209 and 312 preferred terms recorded for each drug. The most frequent AEs for selpercatinib included hepatobiliary disorders (ROR=10.71) and cardiac disorders (ROR=2.33). For pralsetinib, the most common AEs were hepatobiliary disorders (ROR=2.57) and gastrointestinal disorders (ROR=1.53). Compared to pralsetinib, selpercatinib had a more increased risk of serious outcomes (P<0.05).

This study provides critical insights into the established and potential adverse events associated with selpercatinib and pralsetinib. The findings offer valuable evidence to guide the clinical use of RET inhibitors.