Introduction:
An estimated 50% of men with prostate cancer will eventually need androgen deprivation therapy (ADT), but conflicting evidence exists as to whether ADT is associated with dementia or cognitive impairment. Furthermore, the differential risk of first-generation ADT versus next-generation ADT have yet to be explored. Against this backdrop, we examine the association between ADT and dementia or cognitive impairment using VigiBase, the World Health Organization’s unique global database of individual case safety reports (ICSRs).
Methods:
We queried VigiBase, the largest international pharmacovigilance database, for ICSRs of dementia or cognitive impairment (together termed neurocognitive impairment) among men who took ADT between January 1968 and March 2021. ICSRs contain information about patient demographics, general information, drug information and drug reaction. We performed disproportionality analysis for ADT use and neurocognitive impairment. We compared proportion of neurocognitive impairment with ADT use to proportions of neurocognitive impairment with use of all other drugs included in Vigibase. A signal was detected if these proportions were significantly different from each other and was assessed using reporting odds ratio (ROR). Sensitivity analysis was performed for the ADT type. We reported the expected and actual occurrence of neurocognitive impairment and RORs with 95% confidence intervals (95% CI) and lambda values. Lambda values ≥1.0 and p values <0.05 were considered statistically significant. Analyses were performed using R version 4.0.5 and R Studio version 1.4.1106.
Results:
Table 1 shows the demographics of patients experiencing neurocognitive impairment from ADT included in our study population. Table 2 shows the RORs for ADT associated neurocognitive impairment. Reporting rates for next-generation ADT were higher than for first generation ADT (112,034 vs 58,726). Within next-generation agents, enzalutamide, abiraterone, and apalutamide were reported 87,268, 24,334, and 426 times, respectively. Association with neurocognitive impairment was seen for both first- and next-generation ADT but was higher for next-generation ADT (ROR 2.40, 95% CI 2.28-2.54, Q = 2.26) than first-generation ADT (ROR 1.47, 95% CI 1.34-1.62, Q = 1.35).
Within next-generation ADT agents, only enzalutamide had a significantly elevated ROR for neurocognitive impairment (ROR 2.89, 95% CI 2.73-3.05, Q =2.70). Abiraterone had a lower ROR for neurocognitive impairment (ROR 0.68, 95% CI 0.55-0.84, Q = 0.57). Apalutamide had an elevated ROR for neurocognitive impairment approaching significance (ROR 3.31, 95% CI 1.57-7.00, Q =0.98).
Conclusion:
We found next-generation ADT associated neurocognitive impairment to be reported more frequently as well as to have higher ROR of neurocognitive impairment than first-generation ADT. We also found higher ROR of cognitive impairment for enzalutamide but not abiraterone. Taken together, these findings may suggest that patients with significant neurologic comorbidities are better suited for therapy with abiraterone or first-generation ADT over enzalutamide. Due to limitations including those inherent to disproportionality analysis (which only measures associations rather than true risk) and incomplete data prohibiting the ability control for factors such as age or use of secondary drugs, results should be considered exploratory in nature. Further prospective studies of the differential side effect profiles of these agents with a primary cognitive endpoint and in older patients at heightened risk for cognitive impairment is needed to more precisely define the risk of neurocognitive impairment associated with treatment.
Funding: N/A
Image(s) (click to enlarge):
ANDROGEN DEPRIVATION THERAPY IS ASSOCIATED WITH NEUROTOXICITY: A PHARMACOVIGILANCE STUDY
Category
Prostate Cancer > Other
Description
Poster #196
Friday, Dec 3
1:00 p.m. - 2:00 p.m.
Prostate 3
Presented By: Logan Briggs, BA
Authors:
Logan Briggs, BA
Stephen Reese, MD
Peter Herzog, MS
David-Dan Nguyen, MPH
Muhieddine Labban, MD
Khalid Alkhatib, MD
Quoc-Dien Trinh, MD MBA
Alicia Morgans, MD MPH