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The European Medicines Agency’s CHMP has recommended the approval of darolutamide plus ADT in mHSPC in the European Union.
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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the European Union.1
The CHMP decision is supported by data from the phase 3 ARANOTE trial (NCT04736199), which demonstrated that patients who received the darolutamide plus ADT (n = 446) achieved a median radiographic progression-free survival (rPFS) that was not reached (NR; 95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR) among patients treated with placebo plus ADT (n = 223; HR, 0.54; 95% CI, 0.41-0.71; P < .0001).2 The 24-month rPFS rates were 70.3% and 52.1%, respectively.
In June 2025, the FDA approved darolutamide for the treatment of patients with mCSPC.3 The regulatory decision was also supported by data from ARANOTE.
ARANOTE was a global, double-blind study that enrolled adult patients with histologically or cytologically confirmed mHSPC.2 In order to be eligible for the trial, patients needed to have an ECOG performance status of 0 to 2 as well as adequate bone marrow, liver, and renal function. Patients were permitted to have started ADT within 12 weeks of random assignment.
Eligible patients were randomly assigned 2:1 to receive darolutamide at a dose of 600 mg twice daily or matched placebo. All patients received ADT or investigator’s choice of luteinizing hormone-releasing hormone agonist or antagonist or orchiectomy within 12 weeks of the initiation of study treatment.
The primary end point was rPFS per RECIST 1.1 criteria. Secondary end points included overall survival (OS), time to initiation of subsequent systemic anticancer therapy for prostate cancer, time to prostate-specific antigen (PSA) progression, rates of PSA levels of less than 0.2 ng/mL in patients with baseline PSA levels of at least 0.2 ng/mL, and time to pain progression. Study drug was administered until radiographic disease progression, unacceptable toxicity, initiation of new anticancer therapy, patient or physician decision, or study drug interruption exceeding 28 consecutive days.
Additional findings from ARANOTE revealed that the median OS in the investigational and control arms was NR, however there was a trend towards OS benefit in favor of the darolutamide group (HR, 0.81; 95% CI, 0.59-1.12). The 24-month OS rates were 79.8% and 75.5%, respectively. Time to mCRPC (HR, 0.40; 95% CI, 0.32-0.51) and time to PSA progression (HR, 0.31; 95% CI, 0.23-0.41) findings both favored the darolutamide arm.
In terms of safety, any-grade adverse effects (AEs) were reported in 91.0% of patients in the investigational arm and 90.0% of those in the placebo arm. Serious AEs (23.6% vs 23.5%), grade 3 or 4 AEs (30.8% vs 30.3%), grade 5 AEs (4.7% vs 5.4%), and AEs leading to study drug discontinuation (6.1% vs 9.0%) occurred in both arms.
Darolutamide is approved in more than 85 countries for the treatment of patients with mHSPC in combination with ADT, with or without chemotherapy.1 The agent is also approved with ADT alone in patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease.
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