Registry-based randomised phase II study of Enzalutamide versus Abiraterone: assessing cognitive function in eLderly patients with metastatic castration-resistant Prostate cancer (REAL-Pro)

Background Androgen receptor pathway inhibitors (ARPIs) are commonly used in older patients with metastatic castration-resistant prostate cancer (mCRPC). Treatment selection is informed by considering adverse event (AE) profiles, given that there are no previous randomised phase III comparison trials. Materials and methods This prospective registry-based randomised trial utilised the electronic Prostate Cancer Australian Database to collect clinical data. Patients aged ≥75 years who were suitable to receive abiraterone or enzalutamide for mCRPC were randomised to receive either ARPI treatment, stratified by prior docetaxel use. Telephone assessments were conducted at baseline and 12 weeks, including the Blessed Orientation-Memory-Concentration (BOMC) tool, Geriatric Depression Scale (GDS), and Falls Risk Questionnaire (FRQ). Descriptive statistics and mixed-effects linear regression were used to compare groups, including changes in assessment scores from baseline. Cox proportional hazards modelling was used to analyse effects of variables on time to treatment failure (TTF) and overall survival (OS). Results We enrolled 76 men between June 2019 and September 2023, but closed due to slow accrual in December 2023. Nineteen (25%) had prior docetaxel. The median age was 81 years (interquartile range 77-85 years). The mean score change at 12 weeks trended higher in those receiving enzalutamide for each of BOMC (+0.64 versus −0.51, P = 0.46), GDS (+0.70 versus +0.06, P = 0.06), and FRQ (+1.4 versus −0.12, P = 0.06). A higher baseline GDS score was associated with shorter TTF [hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.05-1.6, P = 0.014], as was higher baseline FRQ score (HR 1.12, 95% CI 1.09-1.22, P = 0.012). There were no differences in TTF, OS, prostate-specific antigen response, or AE rates between treatment groups. Conclusions Our results highlight the importance of individualised assessment of cognition, depression, and falls risk in older patients commencing ARPI treatment.