Cognitive effects of androgen receptor (AR) directed therapies for advanced cancer of the prostate (COGCaP): A comparison of enzalutamide vs abiraterone acetate.
Authors: Morgans Alicia K. , Ma Yangruijue , Jackson James C. , Ryan Charles J. , Moses Kelvin A. , Barata Pedro C. , Dorff Tanya B. , Kocherginsky Masha , VanderWeele David James 
Published: February 2025

131

Background:
Whether treatment with androgen receptor pathway inhibitors (ARPIs) with distinct mechanisms of action and central nervous system (CNS) penetration has distinct effects on cognitive function or quality of life (QOL) has been incompletely described. We compared cognitive function and QOL between patients with advanced prostate cancer treated with abiraterone acetate (AA) or enzalutamide (ENZ) in US patients enrolled from one of six sites.
Methods:
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 (AA) were prospectively enrolled. Patients underwent cognitive testing (written and computer-based) and completed patient reported outcome measures (PROMs) 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 PROMs.
Results:
In total 74 of planned 100 participants enrolled: 51 treated with AA and 23 treated with ENZ. Participants were approximately 90% White race, with slightly younger age (70 vs 74 years, p = 0.5) and greater education status (16 vs 13 years, p = 0.2) among AA vs ENZ patients, respectively. Baseline CANTAB and PROs were similar between groups and there were not clinically meaningful changes over time (Table). Median change in all CANTAB module scores was similar between groups at 3, 6 and 12 months, without clinically meaningful change over time (Table).
Conclusions:
No measurable changes were identified on cognitive testing between baseline and 3 months within or between treatment groups, and QOL 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. Clinical trial information:
NCT03016741
.

Example cognitive test and PROM.

Baseline
3 Month
6 Month
12 Month

AA,

N = 48
1

Enz,

N = 20
1

p-value
2

AA,

N = 35
1

Enz, N = 17
1

p-value
2

AA,

N = 34
1

Enz,

N = 15
1

p-value
2

AA N = 25
1

Enz,

N = 13
1

p-value
2

PAL
-0.53 (-1.08, 0.07)
-0.44(-0.88, 0.16)
0.7
0.00 (-0.58, 0.63)
-0.46(-0.65, 0.29)
0.2
0.00(-0.58, 0.65)
0.27(-0.47, 0.78)
0.7
0.00(-0.23, 0.23)
0.00(-0.29, 0.50)
0.9

FACT Cog
128.0(111.0, 136.8)
132.0 (120.5, 138.5)
0.5
-9.0(-17.5, 2.0)
-2.0(-16.2, 3.5)
0.6
-2.0(-13.0, 3.5)
-3.0(-16.0, 4.0)
>0.9
-7.5(-17.5, 2.2)
-1.2 (-6.9, 4.8)
0.4

1
Median (IQR);
2
Wilcoxon rank sum test.