Dr Morgans on the Design of the ARACOG Trial in Prostate Cancer

“We have assessed things like adverse effects and cognitive function within other trials, but having a trial designed specifically to identify this, measure it, and compare between treatment arms is unique.”

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 the design of the phase 2 ARACOG trial (NCT04335682) which evaluated the cognitive effects of enzalutamide (Xtandi) vs darolutamide (Nubeqa) in prostate cancer.

The ARACOG trial was uniquely designed to evaluate cognitive function as its primary end point, representing an important departure from the traditional focus of most oncology clinical trials, Morgans began. Although previous studies have collected data on cognitive outcomes and adverse effects as secondary or exploratory measures, ARACOG was specifically developed to identify, quantify, and directly compare changes in cognitive function between treatment arms, she explained. This dedicated focus allowed investigators to address an issue that is increasingly recognized as highly relevant to patients but has historically received less attention in clinical trial design.

A key strength of the study lies in its methodological and statistical rigor, Morgans said. In many clinical trials, cognitive assessments are included as ancillary measures, meaning that studies are not necessarily powered to detect meaningful differences between treatment groups, she continued. By contrast, ARACOG was designed with cognitive function as the primary objective, ensuring that the statistical framework, including sample size calculations and hypothesis testing, was centered on evaluating cognitive outcomes, she added. This approach strengthens the reliability and interpretability of the findings and allows for more definitive conclusions regarding treatment-related effects on cognition, she concluded.

Patients were randomly assigned to treatment either with darolutamide or with enzalutamide, and they were followed for 48 weeks of total treatment. Morgans presented data from ARACOG in a poster during the 2026 ASCO Annual Meeting. She also reported on the primary end point data, which were collected at 24 weeks following the initiation of treatment.