The Alliance for Clinical Trials in Oncology and the Alliance Foundation Trials (AFT) presented three research studies at the 2026 ESMO Congress, held October 23-26 in Madrid, highlighting advances in prostate and colorectal cancer. Take a look.
2280P – Long-term patient-reported and objective cognitive effects of darolutamide vs enzalutamide in ARACOG (AFT-47)
Presenter: Daniel Kwon, MD (UCSF Health)
Authors: Daniel Kwon, Olivia Bobek, Stephanie Berg, Deepak Kilari, Russell Szmulewitz, Stuart Bloom, Elizabeth Wulff, Karla Ballman, Emmanuel S. Antonarakis, Charles J. Ryan, Alicia K. Morgans
Synopsis: The ARACOG clinical trial compared how two prostate cancer medications, darolutamide and enzalutamide, affect patients’ memory and thinking skills over 48 weeks. Both medications belong to a class of drugs called androgen receptor pathways inhibitors which block the effects of hormones that fuel prostate cancer growth. However, the medications differ in their ability to cross the blood-brain barrier, raising questions about their potential effect on patients’ memory, concentration, and overall quality of life. The trial enrolled 111 patients with advanced prostate cancer, who were randomly assigned to receive darolutamide or enzalutamide. Patients taking darolutamide experienced significantly less decline on objective computer-based cognitive tests and reported fewer noticeable declines in their day-to-day cognitive functioning than those taking enzalutamide, although the difference in patient-reported outcomes did not reach statistical significance.
2244P – Genetic dementia risk and androgen receptor (AR) therapy-associated cognitive effects (ARTACE) results from AFT-47, a randomized comparison of darolutamide (DAR) and enzalutamide (ENZ)
Presenter: Charles J. Ryan, MD (Memorial Sloan Kettering Cancer Center)
Authors: Charles J. Ryan, Daniel Kwon, Olivia Bobek, Stephanie Berg, Deepak Kilari, Jennifer Yokoyama, Russell Szmulewitz, Stuart Bloom, Elizabeth Wulff, Karla Ballman, Emmanuel S. Antonarakis, Alicia K. Morgans
Synopsis: In this follow-up analysis of the ARACOG prostate cancer trial, researchers investigated whether a person’s genetic risk for Alzheimer’s disease might make them more susceptible to cognitive changes associated with the prostate cancer treatments enzalutamide or darolutamide. Using blood samples from 79 patients to calculate an Alzheimer’s disease risk, along with objective computer-based cognitive tests conducted over 24 weeks, researchers found no meaningful link between a patient’s genetic risk score and changes in cognitive performance. Importantly, the differences between treatments remained similar across genetic risk groups, with patients taking enzalutamide continuing to experience greater cognitive decline than those taking darolutamide, indicating that this side effect is not due to patients’ inherited risk for dementia.
858P – ATOMIC (A021502/AIO-KRK-0317): Presentation and outcomes in patients (pts) with stage III d-MMR early-onset colon cancer (EOCC) and average-onset colon cancer (AOCC)
Presenter: Ardaman Shergill, MD, University of Chicago
Authors: Fang-Shu Ou, Christopher H. Lieu, Tyler Zemla, Anwaar Saeed, Dennis Hsu, Andrew B. Nixon, Wendy Frankel, Anke Reinacher-Schick, Walter R. Peters, Khalid Matin, Samara L. Potter, Paul Mehan, Philip J. Gold, Dirk Arnold, Eileen M. O’Reilly, Jeffrey Meyerhardt, Frank A. Sinicrope
Synopsis: This analysis of the ATOMIC trial examined differences in treatment outcomes, safety, and disease characteristics between younger adults (under age 50, classified as early-onset) and older adults (age 50 and older) with stage III mismatch repair-deficient (dMMR) colon cancer. Researchers compared patients treated with standard chemotherapy alone with those receiving chemotherapy plus the immunotherapy drug atezolizumab. The analysis explored whether age influenced the benefits and side effects associated with adding immunotherapy to chemotherapy. The findings provide additional insight into the use of chemoimmunotherapy across different age groups of patients with stage III dMMR colon cancer.