Alicia Morgans, M.D., on cognitive outcomes in the ARACOG trial | ASCO 2026

Cognitive function is emerging as a meaningful differentiator in advanced prostate cancer treatment, and data from the ARACOG trial presented at the 2026 American Society of Clinical Oncology annual meeting add to evidence that not all androgen receptor inhibitors affect the brain the same way.

Alicia K. Morgans, M.D., M.P.H., medical oncologist, director of the Adult Survivorship Program at Dana-Farber Cancer Institute, and principal investigator of the ARACOG trial, discussed the findings in an interview with Managed Healthcare Executive^®. The trial compared Nubeqa (darolutamide) and Xtandi (enzalutamide) on cognitive outcomes, using standardized research measures across several cognitive domains. Nubeqa showed significantly better outcomes in four of the five domains compared with Xtandi; in the fifth, the two treatments performed similarly.

A particularly telling signal came from what researchers call the "learning effect" — the expected improvement in cognitive test scores that occurs simply from taking similar tests repeatedly over time. Patients on Nubeqa showed expected improvement through the 24-week mark, while patients on Xtandi did not.

"When we looked at the enzalutamide-treated arm, we saw that the median score actually stabilized or went down slightly for patients between baseline and 24 weeks, which suggests if that score is stable, these patients aren't necessarily getting better at repeated testing on their cognitive testing, so they may actually be declining in terms of their cognitive function," Morgans said.

The leading hypothesis for the difference in CNS penetration is that Nubeqa is less able to cross the blood-brain barrier and act on androgen receptors in the brain. No patients in the trial were diagnosed with dementia or any clinically recognized cognitive disorder, and Morgans noted that research-grade cognitive measures don't map directly to clinical practice because there is variability between individual patients in the practice setting.

Still, she said, when clinicians have treatment options in the same disease setting, cognitive effects belong in the conversation.

"This is one of the most important things to people, at least in my clinic, in terms of managing themselves, maintaining independence, and being able to care for themselves and the people that they love for as long as possible," Morgans said.