Dr Morgans on the Cognitive Effects of Darolutamide Vs Enzalutamide in Prostate Cancer

“When we compared those maximally changed cognitive domains between the different treatment arms, we found that there was a greater change, or decline, in cognitive function by these Cambridge Neuropsychological Test Automated Battery computer-based cognitive tests for patients treated with enzalutamide than for patients treated with darolutamide, and that was statistically significant.”

Alicia Morgans, MD, MPH, a genitourinary medical oncologist and the medical director of the Survivorship Program at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed data from the phase 2 ARACOG trial (NCT04335682), which evaluated the cognitive effects of enzalutamide (Xtandi) vs darolutamide (Nubeqa) in prostate cancer.

Results from ARACOG demonstrated significant differences in cognitive outcomes between patients treated with enzalutamide and those treated with darolutamide, Morgans began. Using the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized research tool designed to evaluate multiple domains of cognitive function, investigators found that patients receiving enzalutamide experienced a greater decline in cognitive performance compared with those receiving darolutamide, she said. This difference reached statistical significance, suggesting that the 2 androgen receptor pathway inhibitors may have distinct effects on cognitive function, she noted.

The analysis focused on changes in the cognitive domains that showed the greatest variation during treatment. Across these assessments, patients treated with darolutamide generally maintained cognitive function better than those receiving enzalutamide, Morgans said. To further explore these findings, investigators examined individual cognitive modules that measured specific aspects of cognition, such as memory, attention, and executive function. In this analysis, 4 of the 5 evaluated modules showed statistically significant results favoring darolutamide over enzalutamide, providing additional evidence of a potential cognitive advantage with darolutamide treatment, she added.

Importantly, the cognitive assessments used in ARACOG were research-based tools and are not routinely employed in clinical practice, Morgans underscored. The CANTAB platform was selected specifically for its ability to detect subtle changes in cognitive performance in a controlled research setting, she added. As such, the findings should not be interpreted as direct measures of clinically apparent cognitive impairment, she said. Rather, they provide an objective method of identifying potential differences between treatment approaches that may warrant further investigation, she concluded.