Bayer's supplemental new drug application (sNDA) for darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) has been accepted by the FDA for the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This decision is based on the promising results from the phase 3 ARANOTE trial, highlighting the potential of darolutamide to improve outcomes for patients with this condition. The acceptance brings darolutamide closer to becoming an additional treatment option for metastatic HSPC, potentially benefiting a significant number of patients.
The ARANOTE trial, a randomized, double-blind, placebo-controlled study, evaluated the efficacy and safety of darolutamide plus ADT compared to placebo plus ADT in patients with metastatic HSPC. The primary endpoint was radiological progression-free survival (PFS), and secondary endpoints included overall survival (OS), time to castration-resistant event, and time to subsequent anticancer therapy.
Significant Reduction in Disease Progression
The ARANOTE trial demonstrated that darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). Overall survival results also favored darolutamide, with 23.1% of patients in the darolutamide arm dying compared to 26.9% in the placebo arm (HR, 0.81; 95% CI, 0.59-1.12).
Safety Profile
Regarding safety, grade 3 or 4 adverse events (AEs) occurred in 30.8% of patients receiving darolutamide and 30.3% of patients receiving placebo. Deaths due to AEs occurred in 4.7% of the darolutamide group and 5.4% of the placebo group. Anemia, arthralgia, and urinary tract infection were the only AEs to exceed 10% incidence in the darolutamide group.
Expanding Treatment Options
"Today’s acceptance of our sNDA application for [darolutamide] plus ADT for the treatment of patients with [metastatic] HSPC brings us closer to adding an additional treatment option for [darolutamide] to benefit those living with [metastatic] HSPC," said Christine Roth, executive vice president of Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership team at Bayer. "If approved, this would expand the indication for [darolutamide] in patients with [metastatic] HSPC to include [darolutamide] both with and without chemotherapy, providing physicians and their patients with an additional [darolutamide] treatment option in this setting."
Trial Design and Patient Population
The ARANOTE trial enrolled 669 male patients aged 18 or older with histologically or cytologically confirmed adenocarcinoma of the prostate and metastatic disease. Patients had to have started ADT with or without first-generation anti-androgen agents no earlier than 12 weeks before randomization. The experimental arm received 600 mg of darolutamide twice daily with food and investigator’s choice of ADT, while the placebo arm received placebo twice daily with food and investigator’s choice of ADT.
Ongoing Clinical Development
Darolutamide is also being investigated in the phase 3 ARASTEP trial (NCT05794906) in HSPC with high-risk biochemical recurrence and the phase 3 DASL-HiCAP trial (NCT04136353) as an adjuvant treatment for localized prostate cancer with a high risk of recurrence. These trials could further expand the clinical utility of darolutamide in prostate cancer management.
