medwireNews: Both traditional hormone therapy and novel androgen receptor signaling inhibitors (ARSIs) may be associated with neurocognitive impairment in men with prostate cancer, suggests WHO pharmacovigilance data.
The association was stronger for ARSIs than traditional therapies (androgen deprivation therapy [ADT] or first-generation androgen receptor antagonists) and for enzalutamide versus abiraterone.
The findings conflict with some previous reports but the researchers say that “[t]he amalgamation of these and other conflicting data may contribute to clinical decision-making for men with prostate cancer eligible for treatment with these therapies, especially those with significant neurologic comorbidities.”
Using VigiBase, the WHO’s global database of individual case safety reports, Alicia Morgans (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues identified 1762 neurocognitive adverse drug reactions (ADRs) associated with the use of traditional hormone therapy or novel ARSIs in men between 1968 to 2021.
Of these, 20% were associated with traditional hormone therapy and 80% were associated with novel ARSIs. Among the ADRs associated with novel ARSIs, the majority (93%) were among people using enzalutamide, with 6% occurring in abiraterone users and 1% in apalutamide users.
The researchers measured differences in neurocognitive impairment rates with reporting odds ratios (RORs) and a disproportionality analysis, which they say allows them “to compare the proportion of individuals who experience neurocognitive ADRs after using hormone therapy with the proportion of individuals who experience neurocognitive ADRs after using all other drugs included in VigiBase.”
They report in Prostate Cancer and Prostatic Diseases that the RORs for neurocognitive impairment were significantly elevated with both traditional hormone therapy (ROR=1.47) and novel ARSIs (ROR=2.40), but the association was significantly greater with the novel versus traditional treatments.
When neurocognitive impairment was separated into cognitive impairment and dementia, there was also a stronger association with the novel ARSIs than with traditional hormone therapy (ROR=2.30 vs 1.26) for cognitive impairment. Conversely, there was no difference between the two treatment groups for dementia-related ADRs (ROR=3.56 vs 4.01) but the RORs were still significantly elevated relative to all other drugs.
Further analysis showed that the increased risk for neurocognitive ADRs with novel ARSIs was driven by enzalutamide as opposed to apalutamide or abiraterone. In this case, the ROR for enzalutamide was a significant 2.89 while that for apalutamide was a nonsignificant 3.31, likely due to small numbers of cases, the researchers note.
By contrast, the odds for neurocognitive impairment were significantly lower with abiraterone than with other drugs, at an ROR of 0.68.
Morgans and co-authors conclude that their “study demonstrates elevated odds of neurocognitive impairment with hormone therapy in a real-world data set.”
However, they stress that “limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs (e.g., concurrent use of novel ARSIs with ADT)” mean that their findings “are exploratory in nature.”
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Prostate Cancer Prostatic Dis 2022; doi:10.1038/s41391-022-00541-6