Abstract
Background
ALK/ROS1 tyrosine kinase inhibitors (TKIs) have improved outcomes in molecularly selected malignancies, but trial populations do not fully represent the age and clinical heterogeneity encountered in routine care. Comparative post-marketing evidence on age-related and drug-specific reporting patterns remains limited.
Methods
We analyzed US Food and Drug Administration Adverse Event Reporting System data from 2004 Q1 through 2026 Q1. The study included 38,479 primary-suspect reports with known age for crizotinib, entrectinib, brigatinib, lorlatinib, repotrectinib, cabozantinib, or ceritinib. Reports were stratified as 0–17, 18–44, 45–64, or ≥65 years. A preferred term (PT) was considered positive only when prespecified criteria for ROR, PRR, BCPNN, and MGPS were all met. We evaluated formal drug-exposure-by-age interactions, drug-level PT-spectrum similarity, clinical priority, and reported time to onset (TTO) with Weibull modeling.
Results
Positive PT counts were 64, 159, 230, and 178 across the four age groups, respectively, and 299 in the all-age analysis. Of 255 PTs eligible for formal interaction testing, 127 had an interaction false-discovery rate
Conclusion
These findings support surveillance based on both age and the prescribed agent rather than a uniform class profile. The early reporting pattern favors close assessment soon after treatment initiation. FAERS signals remain hypothesis-generating and require confirmation in longitudinal patient-level data.