Dr Morgans on Cognitive Effects of Darolutamide vs Enzalutamide in Prostate Cancer

Alicia Morgans, MD, MPH, discusses results from the ARACOG trial (NCT04335682), which compared changes in cognitive function with enzalutamide (Xtandi) and darolutamide (Nubeqa) in patients with advanced prostate cancer, and explains how these data can be brought into shared decision-making conversations. In this discussion, Morgans walks through the ARACOG design and findings, as well as how cognitive health factors into her treatment conversations with patients.

Morgans, a genitourinary medical oncologist at Dana-Farber Cancer Institute, notes that ARACOG was recently reported at the 2026 ASCO Annual Meeting. The trial assessed change in cognitive function from baseline to 24 weeks among patients with advanced prostate cancer who were randomized to enzalutamide or darolutamide.

The results showed a greater decline in cognitive function with enzalutamide in 4 of 5 measured cognitive domains. The investigators also examined the maximally changed cognitive domain, meaning the domain most affected in either treatment arm. There too, the decline was significantly greater with enzalutamide compared with darolutamide. These changes were measured against each patient’s own baseline.

Morgans describes how she would incorporate these findings in clinical practice. She would consider each patient’s cognitive function at baseline and talk with patients about whether cognitive function is an important factor as they make treatment decisions. She would also include the ARACOG data in that discussion, particularly for patients who need to maintain excellent cognitive function. She views this as one component of a conversation and a shared decision that many patients may find especially important.

Looking ahead, Morgans outlines where clinical research in metastatic hormone-sensitive prostate cancer (mHSPC) is heading. She says studies will continue to explore molecular heterogeneity and the differences between patient populations with mHSPC, since one label does not describe every patient.

She also expressed enthusiasm for quality-of-life and side-effect analyses, particularly those focused on cognitive health, because they already inform conversations in the clinic today. The next updates from ARACOG will include longer-term data describing cognitive change over time. They will also include patient-reported outcome information that captures how patients themselves experience their cognitive function.