ARANOTE trial

The randomized, phase III ARANOTE study compares the combination of darolutamide with androgen deprivation therapy (ADT) to ADT alone in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). During ESMO 2024, Prof Dr Fred Saad (Centre Hospitalier de l’Université de Montréal, Montréal, Canada) presented the primary results of this trial.

In total, 669 patients with mHSPC and an ECOG performance status of 0-2 were randomly assigned (2:1) to receive darolutamide (600 mg bid) + ADT or ADT alone. The study convincingly met its primary endpoint by demonstrating a significant 46% reduction in the risk for radiologic progression with the darolutamide-ADT combination (2-year rates: 70.3% vs. 52.1%; HR[95%CI]: 0.54[0.41-0.71]; p< 0.0001). This benefit was seen irrespective of age, baseline PSA value, Gleason score at diagnosis, or disease volume and regardless of the presence of visceral metastases or prior use of local therapy. The addition of darolutamide to ADT also provided a significant benefit in terms of time to castration-resistance, time to PSA progression, time to subsequent systemic therapy for prostate cancer and time to pain progression. Data for overall survival are immature, but indicate a (non-significant) 19% lower death risk for patients in the darolutamide-ADT arm (HR[95%CI]: 0.81[0.59-1.12]).

Importantly, this clinical benefit did not come at the cost of additional toxicity, with a similar rate of grade ≥3 adverse events and even a lower rate of adverse events leading to treatment discontinuation in the darolutamide arm (6.1% vs. 9.0%). Strikingly, also the incidence of grade ≥3 fatigue was lower in the experimental arm compared to ADT alone at 5.6% and 8.1%, respectively.

As such, the primary results of ARANOTE mark darolutamide + ADT, without docetaxel, as an additional standard of care for patients with mHSPC.