Alicia Morgans, MD, discusses cognitive effects of darolutamide vs enzalutamide in prostate cancer

Added: 2026-06-07

[00:00:02][music] [bell] >> This study was designed to understand whether there may be differences in cognitive effects between two treatments. They're both androgen receptor pathway inhibitors for advanced prostate cancer, darolutamide and enzalutamide, and patients were randomized to receive one of these and were followed prospectively with computer-based cognitive tests as well as patient-reported outcomes and some additional assessments to understand whether there may be a difference. And I think importantly, the primary endpoint for ARAS was change in cognitive function from baseline. So, having this as the primary endpoint, I think ensures that we have the appropriate statistical power and methodology to understand what can be a very complex primary endpoint.

[00:01:07]So, we found within this comparison that at 24 weeks, which is approximately 6 months, there was a greater change in the maximally changed cognitive domain for patients treated with enzalutamide than with darolutamide. And let me unpack that a little bit. So, there were five CANTAB, which is a company that does computer-based cognitive testing, five CANTAB modules. And because cognitive function is such a complex construct, there can be overlap in these cognitive test modules for different aspects of cognitive function, including things like executive function, attention, working memory, and visual memory.

[00:01:48]So, we designed from the beginning that we would look at the worst cognitive test, so the module that was the worst in each treatment arm, so that we didn't give an unfortunate or or unwitting advantage to either arm and just understand which module was most affected in both arm and both treatment arms and compare those maximally changed cognitive domains. So when I say that there was a greater change in enzalutamide it was actually a different cognitive test module that had a greater change but it was the maximally changed cognitive domain that was the primary endpoint in this trial.

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