Expanding Options in mHSPC: Morgans Discusses ARANOTE Trial

The ARANOTE trial (NCT04736199) represents a significant step forward in the treatment landscape for patients with metastatic hormone-sensitive prostate cancer (mHSPC). The study aimed to explore the potential of darolutamide (Nubeqa) when combined with androgen deprivation therapy (ADT) as a doublet regimen, without the use of chemotherapy.

This clinical trial was born out of a need to better understand treatment pathways for patients who may not be suitable for, or interested in, chemotherapy. While the ARASENS trial (NCT02799602) had previously established the efficacy of darolutamide in combination with both ADT and docetaxel, not every patient can tolerate docetaxel. The ARANOTE trial sought to fill that knowledge gap by evaluating whether darolutamide plus ADT alone could offer similar benefits to a broader patient population.

In this randomized study, patients received either ADT in combination with darolutamide or ADT with a placebo. The primary end point was radiographic progression-free survival (rPFS), which serves as a key measure of how long a treatment can prevent the cancer from worsening on imaging.​​

Results from the primary analysis were promising. The addition of darolutamide significantly improved rPFS compared with ADT alone, with a hazard ratio of 0.54, demonstrating a nearly 50% reduction in the risk of disease progression. Importantly, this clinical benefit did not come at the cost of increased toxicity.

In fact, one particularly encouraging outcome was that fatigue, a common and clinically relevant adverse event, was actually reported less frequently in the darolutamide group than in those receiving ADT and placebo. While this does not suggest an energizing effect, it does support the tolerability of the regimen and reinforces its potential use in a wide range of patients.

The ARANOTE trial has helped reinforce the role of darolutamide as a flexible and well-tolerated treatment option in mHSPC, broadening the conversation around patient-centric, chemotherapy-free approaches. In an interview with Targeted Oncology, Alicia Morgans, MD, MPH, genitourinary medical oncologist and director of the Survivorship Program at Dana-Farber Cancer Center and associate professor of medicine at Harvard Medical School, further discusses the trial.

REFERENCE:

Morgans A, Haresh KP, Jievalta M, et al. Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial. J Clin Oncol. 2025;43(suppl 16):abstr 5004. doi:10.1200/JCO.2025.43.16_suppl.5004