Darolutamide With Androgen Deprivation Therapy Improves OS in Nonmetastatic CRPC

Darolutamide and androgen deprivation therapy improved overall survival compared with placebo in patients with nonmetastatic castration-resistant prostate cancer, meeting one of the end points of the phase III ARAMIS study, Bayer announced in a press release.

Darolutamide (Nuebeqa) and androgen deprivation therapy (ADT) improved overall survival (OS) compared with placebo in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), meeting one of the end points of the phase III ARAMIS study (NCT02200614), Bayer announced in a press release.1

Darolutamide, an AR inhibitor, was previously approved by the FDA for the treatment of patients with nmCRPC based on the ARAMIS study. The previously reported data showed that darolutamide plus androgen deprivation therapy (ADT) led to a higher median metastasis-free survival versus placebo plus ADT, meeting the primary end point of the trial and leading to approval of the agent in this patient population.2

The median MFS was 40.4 months with darolutamide plus ADT versus 18.4 months in the placebo-plus-ADT arm (HR, 0.41; 95% CI, 0.34-0.50,P<.0001). The OS data were not mature at the time of MFS assessment.1

Adverse events (AEs) were more frequent in the darolutamide arm. The most common AEs observed overall were fatigue (16% vs11%), pain in extremities (6% vs 3%), and rash (3% vs 1%) in the darolutamide and control arms, respectively.

Serious AEs occurred in 25% of patients in the darolutamide arm and in 20% of those in the ADT-alone arm. Serious AEs occurring in more than 1% of patients treated with darolutamide were urinary retention, pneumonia, and hematuria. Deaths occurred in 3.9% of patients who received darolutamide, which included natural causes (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). In the ADT arm, 3.2% of patients died due to serious AEs.

Two percent or more of patients in the darolutamide arm experienced clinically significant AEs, which compared with placebo, included ischemic heart disease (4.0% vs. 3.4%) and heart failure (2.1% vs. 0.9%).

ARAMIS is an ongoing, randomized, double-blind, placebo-controlled, multicenter study, which is evaluating the efficacy and safety of oral darolutamide in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone analog or had a bilateral orchiectomy. The study includes 1,509 patients who were randomized 2:1 to receive either darolutamide 600 mg orally twice daily plus ADT or placebo plus ADT. The secondary end points of the study include OS, time to pain progression, time to initiation of first cytotoxic chemotherapy for prostate cancer, and time to the first symptomatic skeletal event.

The study has completed enrollment of patients with histologically or cytologically confirmed prostate cancer without neuroendocrine differentiation or small cell features, and castration-resistant prostate cancer with castrate level of serum testosterone. Patients were eligible to enroll if they had a prostate-specific antigen (PSA) doubling time of ≤10 months and PSA >2 ng/ml, and an ECOG performance status of 0 to 1, hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1500/µl, platelet count ≥100,000/µl, and alanine aminotransferase and/or aspartate transaminase ≤2.5 × upper limit of normal (ULN), total bilirubin ≤1.5 × ULN, creatinine ≤2.0 × ULN.

Individuals with nmCRPC were excluded from the study if they had a history or presence of metastatic disease at any time; acute toxicities from prior treatments or procedures that were not resolved to grade ≤1 or baseline before randomization; and prior treatment with either second-generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor, or chemotherapy or immunotherapy for prostate cancer. The other exclusion criteria were related to comorbidities and diseases or infections that may have interfered with treatment.

Bayer, the developer of the drug, plans to submit applications for approval to regulatory organizations in the European Union and other regions. Darolutamide is also under investigation in the ongoing phase II ARASENS study (NCT02799602), which is evaluating darolutamide added to ADT and docetaxel for the treatment of metastatic hormone-sensitive prostate cancer.

The OS findings from the ARAMIS trial, along with the other efficacy end points, will be reported at an upcoming scientific meeting. Data from longer term follow-up on safety will also be reported in the future.


  1. Nebeqa (darolutamide) plus androgen deprivation therapy achieved the secondary endpoint of overall survival (os) in men with non-metastatic castration-resistant prostate cancer [new release]. Whippany, MJ: Bayer; January 30, 2020. https://bit.ly/36AKC3z . Accessed January 30, 2020.
  2. LFDA approves darolutamide for non-metastatic castration-resistant prostate cancer [news release]. FDA website. https://bit.ly/36F0LVB. Accessed Janaury 30, 2020.