Clinical Summary: 

• Design/Context: In this open-label study, researchers compared darolutamide plus ADT with a propensity score–matched ADT control arm from the CHAARTED trial in metastatic hormone-sensitive prostate cancer.
• Key Outcomes: Darolutamide plus ADT significantly improved progression-free survival, overall survival, radiographic progression-free survival, and time to metastatic castration-resistant prostate cancer.
• Clinical Relevance: These findings reinforce the efficacy and safety of darolutamide plus ADT in mHSPC and support its use as a standard treatment option in this setting.

Rana McKay, MD, University of California, San Diego, California, discusses results from the ARASEC trial evaluating darolutamide plus androgen deprivation therapy (ADT) among patients with metastatic hormone-sensitive prostate cancer. 

Results demonstrated that this combination significantly improves survival and disease control in metastatic hormone-sensitive prostate cancer. 

Dr McKay presented these results at the 2026 American Urological Association (AUA) Annual Meeting in Washington, District of Columbia.

Transcript: 

Hi, my name is Rana McKay, and I’m a genitourinary medical oncologist at the University of California, San Diego. I’m excited to share with you our study of darolutamide plus ADT in mHSPC, the ARASEC trial.

This study was designed at a time when the treatment landscape for patients with mHSPC was undergoing dramatic changes and combination therapy with either ADT/ARPI or ADT plus docetaxel was becoming the new standard of care. There were evolving data regarding darolutamide’s activity in other disease contexts, and there was tremendous interest among clinicians and patients alike to investigate darolutamide in the mHSPC setting. However, conducting a trial in the United States with an ADT-alone control arm was really not possible, and therefore the ARASEC study was designed.

ARASEC is an open-label study comparing a prospectively enrolled darolutamide arm versus an external ADT arm from CHAARTED. Patients enrolled received darolutamide plus ADT. The inclusion criteria were aligned with those of the CHAARTED trial, the schedule of events was aligned with CHAARTED, and the primary end point, progression-free survival, also aligned with the endpoint definition from CHAARTED. 

Given differences in baseline characteristics between ARASEC and CHAARTED, patients were matched 1:1 using propensity scores accounting for age, ECOG performance status, extent of disease, prior local therapy, Gleason score, and baseline PSA. The matching helped ensure that patients with similar scores were compared between the 2 arms. After matching, there were 160 patients in each arm. The matching resulted in well-balanced treatment arms across the key variables evaluated.

The ARASEC study was positive and met its primary end point, demonstrating significantly improved progression-free survival with darolutamide plus ADT versus ADT alone, with a statistically significant hazard ratio of 0.29. Additionally, key secondary end points favored the combination. The combination resulted in significantly improved overall survival, with a hazard ratio of 0.5, which was also statistically significant. This overall survival benefit was achieved despite proportionally more patients in the ADT arm receiving subsequent life-prolonging therapies compared with the darolutamide arm.

Other key secondary end points were also improved, including time to mCRPC and radiographic progression-free survival. The hazard ratio for time to mCRPC was 0.26, and for radiographic progression-free survival it was 0.3, both statistically significant. In addition, a large proportion of patients receiving combination therapy achieved a PSA nadir of less than 0.2 at any time on study, that was at 68% in the combination arm compared with 33% with ADT monotherapy from CHAARTED.

We conducted several sensitivity analyses given the limitations of the trial design. We evaluated whether darolutamide plus ADT would perform similarly compared with a contemporary ADT arm, using the ARANOTE trial for that analysis. These sensitivity analyses further supported the study findings. Additional analyses looking at unmatched patients also supported the robustness of the results, with hazard ratios consistently favoring the combination.

Safety data from CHAARTED were not tabulated, so we relied on safety data from ARANOTE and demonstrated a safety profile very similar to ADT monotherapy.

In conclusion, ARASEC provides further evidence for the efficacy and safety of darolutamide plus ADT in mHSPC, reinforcing the findings from ARANOTE in a US population. The combination resulted in significant improvements in progression-free survival, overall survival, and PSA response, and the sensitivity analyses further support the robustness of these findings. To our knowledge, this is the first prostate cancer study utilizing propensity score matching with external phase 3 trial controls. 

Source: 

McKay RR, Ross AE, Preston MA, et al. Darolutamide plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (MHSPC): ARASEC – US prospective, open-label phase 2 study with an external control arm. J Urol. Published online: May 1, 2026. doi:10.1097/01.JU.0001192572.07890.f8.08