Impact of abiraterone versus enzalutamide on depression and anxiety in hormone-sensitive prostate cancer (HSPC).

147 Background: Abiraterone (A) and enzalutamide (E) are now standard of care options for localized high risk and metastatic HSPC. Prior work in castration resistant disease suggested increased risk for depression with E compared to A. The impact of A v. E on depression and anxiety in HSPC where A/E are used for longer and have greater survival benefit is unknown. Methods: We used clinical data from an academic health system to identify patients who received ADT and either A or E as first-line therapy for HSPC from 2018-2024. Baseline characteristics were compared using t-, Chi-square, and Fisher’s exact tests. Outcomes were 1) clinical encounters for depression or anxiety and 2) psychotropic drug fills while on A/E. We restricted the cohort to those without baseline depression or anxiety diagnoses or psychotropic drug fills. Using logistic regression, we compared the odds of having the outcomes as a function of receiving A v. E; we controlled for age, race, cancer stage (N0/N1 v. metastatic), Charlson comorbidity index (CCI), year of A/E initiation, and time on A/E. We fitted a second logistic regression model to the full cohort and added baseline depression or anxiety and psychotropic drug fills as covariates. Results: Out of 412 patients with HSPC, 342 received A and 70 E. Patients who received E were more likely to have metastatic HSPC (89 v. 71%, p<0.01), start treatment later during the study period (56 v. 52% in 2022-2024, p=0.03), and have baseline depression (14 v. 4%, p<0.01). There was no difference in age, race, CCI, baseline anxiety, or time on A/E. In the subgroup without baseline depression or anxiety or psychotropic drug fills, patients on E had higher odds of a new depression diagnosis (aOR 3.12, 95% CI 1.10-8.88) than those on A (Table). There was no difference in odds of a new anxiety diagnosis (aOR 1.29, 95% CI 0.42-3.99) or psychotropic drug fill (aOR 2.08, 95% CI 0.79-5.45). When accounting for baseline depression or anxiety and psychotropic drug fills in the full cohort, patients on E had higher odds of a clinical encounter for depression (aOR 3.07, 95% CI 1.22-7.74, p=0.02) and a psychotropic drug fill (aOR 2.26, 95% CI 1.03-4.95, p=0.04) than those on A. There was no difference in odds of a clinical encounter for anxiety (aOR 1.69, 95% CI 0.67-4.28, p=0.27). Conclusions: Patients who received E for HSPC were more likely to experience clinically relevant depression, but not anxiety, than those who received A. Incident depression and anxiety in patients on A v. E for HSPC. Abiraterone(n, %) Enzalutamide(n, %) Adjusted OR (95% CI) Adjusted p-value DepressionA: n = 330, E: n = 60* 20 (6%) 8 (13%) 3.12 (1.10-8.88) 0.03 AnxietyA: n = 324, E: n = 63 20 (6%) 5 (8%) 1.29 (0.42-3.99) 0.66 Psychotropic drug fillA: n = 257, E: n = 50 25 (10%) 9 (18%) 2.08 (0.79-5.45) 0.14 *Cohort sizes differ for each outcome as analyses were restricted to patients without that outcome at baseline.