Dr Morgans on the Rationale for Evaluating Darolutamide Plus ADT in High-Risk Biochemical Recurrence of Prostate Cancer

“The hope is that we’re going to prolong the time to PSMA PET progression. This is an important end point that would be paradigm-shifting from a regulatory standpoint; this has not been an end point that has been used before, [which] is an exciting opportunity for us in the prostate cancer field to understand more clearly how PSMA PET progression may be associated with other outcomes, including metastasis-free survival by conventional imaging, which is also a key secondary end point."

Alicia Morgans, MD, MPH, an associate professor of medicine at Harvard Medical School and the medical director of the Survivorship Program at the Dana-Farber Cancer Institute, discussed the mechanistic rationale for evaluating darolutamide (Nubeqa) plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence of prostate cancer.

The phase 3 ARISTEP study (NCT05794906) was an international trial that included patients with biochemical recurrence of their prostate cancer following primary treatment of radiation or a prostatectomy, Morgans began. She noted that the study included patients who at a high-risk biochemical recurrence, which was high-risk because of prostate-specific membrane antigen (PSMA) PET–positive metastatic disease. Patients were randomly assigned to either receive ADT for 2 years or ADT plus darolutamide for 2 years, she explained. Of note, patients could also have received metastasis-directed radiation to areas that are PSMA PET–positive per recommendation from their physician, she added.

Historically, androgen receptor pathway inhibitors have improved outcomes in patients with metastatic hormone-sensitive prostate cancer (HSPC), nonmetastatic castration-resistant prostate cancer (CRPC), metastatic CRPC, and in the nonmetastatic HSPC setting with enzalutamide (Xtandi) in the phase 3 EMBARK trial (NCT02319837), according to Morgans. She emphasized that various studies have demonstrated that targeting the androgen receptors shows benefit in patients with prostate cancer.

The purpose of evaluating the combination of darolutamide and ADT was to observe whether it could prolong the time to PSMA PET progression, which could potentially be a shift in the prostate cancer treatment paradigm, Morgans continued. Of note, radiographic progression-free survival has not been previously used as an end point, which is a significant opportunity in the prostate cancer landscape, especially to further understand how PSMA PET is associated with other outcomes, she concluded.