(UroToday.com) The 2025 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Alicia Morgans discussing COGCaP, assessing the cognitive effects of enzalutamide versus abiraterone acetate for advanced prostate cancer. Whether treatment with androgen receptor pathway inhibitors with distinct mechanisms of action and central nervous system (CNS) penetration has distinct effects on cognitive function or quality of life has been incompletely described. Abiraterone acetate is a steroid synthesis inhibiting agent that decreases testosterone production from the adrenal glands, without evidence of CNS penetration or direct effects. Enzalutamide is an androgen receptor antagonist with blood brain barrier penetration and presumed androgen receptor antagonist effects in the CNS. At GU ASCO 2025, Dr. Morgans and colleagues compared cognitive function and quality of life between patients with advanced prostate cancer treated with abiraterone acetate or enzalutamide in US patients enrolled from one of six sites.
Patients with metastatic hormone sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC) or non-metastatic castration-resistant prostate cancer (nmCRPC) who were initiating treatment with enzalutamide or abiraterone acetate were prospectively enrolled. Patients underwent cognitive testing (written and computer-based) and completed patient reported outcome measures at baseline, 3, 6, and 12 months:
The primary endpoint compared median changes in CANTAB computer-assessed cognitive function between groups at 3 months, and secondary endpoints included comparison of longitudinal cognitive function and patient reported outcome measures.
In total 74 of planned 100 participants enrolled, including 51 treated with abiraterone acetate and 23 treated with enzalutamide. Participants were approximately 90% white race, with slightly younger age (70 versus 74 years, p = 0.5) and greater education status (16 versus 13 years, p = 0.2) among abiraterone acetate vs enzalutamide patients, respectively:
Baseline CANTAB and patient reported outcomes were similar between groups and there were not clinically meaningful changes over time. Median change in all CANTAB module scores was similar between groups at 3, 6 and 12 months, without clinically meaningful change over time:
Dr. Morgans concluded her presentation discussing COGCaP, assessing the cognitive effects of enzalutamide vs abiraterone acetate for advanced prostate cancer with the following take-home points:
- No measurable changes were identified on cognitive testing between baseline and 3 months within or between treatment groups, and quality of life decreased minimally over time and was similar between treatment groups despite different effects of treatment in the CNS
- Reasons may include lack of difference in effect between agents or an inability to detect differences with existing measures in an all-comers population not enriched for patients most vulnerable to cognitive change
- Further analyses of genetic factors and functional MRI studies associated with cognitive change are ongoing
Presented by: Alicia K. Morgans, MD, MPH, Dana-Farber Cancer Institute, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.