E-News - June 2026
Spotlight on Alliance Trials
News Release
AFT Study Finds Some Prostate Cancer Drugs Related to More Cognitive Decline
ARACOG TRIAL reveals patients taking hormone therapy darolutamide had less mental decline compared to men taking enzalutamide for advanced prostate cancer
June 17 -- A new randomized Alliance Foundation Trials (AFT) clinical study found that men with advanced prostate cancer taking the hormone therapy medication darolutamide had less cognitive decline compared to men taking enzalutamide.
According to results from the ARACOG (AFT-47) phase II trial, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2026, patients taking enzalutamide experienced significantly greater cognitive decline than those taking darolutamide over a 24-week period.
“This is the first randomized comparison of American patients receiving enzalutamide or darolutamide for advanced prostate cancer that compares cognitive effects as the primary endpoint,” said Alicia Morgans, MD, MPH, lead author on the study and Director of the Survivorship Program at Dana-Farber Cancer Institute. “Enzalutamide and darolutamide work similarly in terms of prostate cancer control. However, knowing that there can be differences in cognitive effects between these drugs may affect treatment choice if both options are available.”
Both medications are widely used androgen receptor pathway inhibitors, designed to starve prostate cancer cells of the hormones they need to grow. However, because the the degree to which these therapies can cross the blood-brain barrier can vary, scientists have questioned whether the medications might subtly impact a patient’s memory, focus, and overall quality of life.
The ARACOG study, initiated by AFT in 2020, aimed to find an answer. Between 2021 and 2025, the trial enrolled 111 patients with various stages of advanced prostate cancer across the United States. Patients were randomly assigned to receive either darolutamide or enzalutamide.
To measure cognitive performance, researchers used CANTAB, a validated, highly sensitive computer-based testing platform that employs five distinct test modules assessing specific cognitive domains found to be affected during treatment with hormonal therapy, including memory recall, spatial working memory, and executive function.
At the 24-week mark, 95 patients were fully evaluable for the study's primary endpoint: measuring the percentage of change in a patient’s “maximally changed cognitive domain” (the mental area where they suffered the steepest drop). The differences were notable:
- Enzalutamide patients saw a median cognitive decline of 36.1%.
- Darolutamide patients saw a median cognitive decline of 15.8%.
The findings were statistically significant. Furthermore, researchers noted that patients taking darolutamide appropriately experienced the “learning effect,” meaning their scores slightly improved on subsequent tests as they got used to the test. Scores for patients taking enzalutamide, by contrast, remained flat or showed a mild drop-off.
Why the Findings Matter
For the thousands of men undergoing advanced prostate cancer treatment, the findings present a critical trade-off for patients to discuss with their treatment teams. Many men with advanced prostate cancer can manage their disease for years, sometimes more than a decade, making long-term quality of life and independent living a primary concern for patients, many of whom are older (the median age in the trial was 71).
The research team stated that longer-term tracking of these cognitive changes, as well as deeper analyses of patient-reported quality-of-life data, is actively ongoing.
In addition to the Dana-Farber Cancer Institute, researchers on the project were from the Froedtert & the Medical College of Wisconsin Clinical Cancer Center; Helen Diller Family Comprehensive Cancer Center, University of California; Mayo Clinic; Memorial Sloan Kettering Cancer Center; University of Chicago Medical Center; University of Kansas Medical Center; and the University of Minnesota Medical School.
Conducted by the AFT, research funding for this project came from the Prostate Cancer Foundation, Alliance Scholar Award, and Bayer.
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Reference: Cognitive effects of darolutamide vs enzalutamide: Results of ARACOG (AFT-47), a randomized clinical trial from the Alliance for Clinical Trials in Oncology, ASCO 2026, Oral Abstract #5005, Journal of Clinical Oncology, DOI: 10.1200/JCO.2026.44.16_suppl.5005
Alliance Foundation Trials, LLC, is a research organization that develops and conducts cancer clinical trials, working closely with the Alliance for Clinical Trials in Oncology scientific investigators and institutional member network, research collaborators, and non-NCI funding sources. AFT seeks to fulfill the vision of the Alliance for Clinical Trials in Oncology to reduce the impact of cancer on people by uniting a broad community of scientists and clinicians from many disciplines committed to discovering, validating and disseminating effective strategies for the prevention and treatment of cancer. Current AFT studies are funded by industry collaborators and the Patient-Centered Outcomes Research Institute (PCORI).
The Alliance for Clinical Trials in Oncology is a national leader in advancing cancer research, uniting more than 25,000 cancer specialists at 115 main institutions and 1,400 affiliates across the U.S. and Canada. As part of the National Clinical Trials Network and a leading research base for the NCI Community Oncology Research Program, the Alliance conducts pioneering, practice-changing clinical trials that improve outcomes and reshape standards of care. Our work has led to multiple FDA approvals, influenced national guidelines, and produced hundreds of high-impact publications. More than 40,000 participants have taken part in Alliance studies, and our growing biospecimen repository now includes more than 1.5 million samples, collected over the past 30 years. Learn more at allianceforclinicaltrialsinoncology.org.
