Impact of darolutamide on local symptoms: pre-planned and post hoc analyses of the ARAMIS trial

Neal D. Shore, Arnulf Stenzl, Christopher Pieczonka, Zachary Klaassen, William J. Aronson, Lawrence Karsh, Charles J. Ryan, Jorge Ortiz, Shankar Srinivasan, Ateesha F. Mohamed, Frank Verholen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: To assess, the effect of darolutamide (a structurally distinct androgen receptor inhibitor) on urinary and bowel symptoms, using data from the phase III ARAMIS trial (NCT02200614) that showed darolutamide significantly reduced the risk of metastasis and death versus placebo. Patients and Methods: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554). Local symptom control was assessed by first prostate cancer-related invasive procedures and post hoc analyses of time to deterioration in quality of life (QoL) using total urinary and bowel symptoms, and individual questions for these symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module subscales and Functional Assessment of Cancer Therapy-Prostate prostate cancer subscale. Prostate-specific antigen (PSA) responses were correlated with urinary and bowel adverse events (AEs). Results: Fewer patients receiving darolutamide (4.7%) versus placebo (9.6%) underwent invasive procedures, and time to first procedure was prolonged with darolutamide (hazard ratio 0.42, 95% confidence interval 0.28–0.62). Darolutamide significantly (P < 0.01) delayed worsening of QoL for total urinary and bowel symptoms versus placebo, mostly attributed by individual symptoms of urinary frequency, associated pain, and interference with daily activities. AEs of urinary retention and dysuria were less frequent with darolutamide, and greater PSA response (≥90%, ≥50% and <90%, <50%) among darolutamide-treated patients was associated with lower incidences of urinary retention (2.2%, 4.2%, 5.1%) and dysuria (0.5%, 3.2%, 5.1%), respectively. Conclusions: Darolutamide demonstrated a positive impact on local disease recurrence and symptom control in patients with nmCRPC, delayed time to deterioration in QoL related to urinary and bowel symptoms, and a favourable safety profile showing similar incidence of urinary- and bowel-related AEs compared with placebo.

Original languageEnglish (US)
Pages (from-to)452-460
Number of pages9
JournalBJU International
Issue number4
StatePublished - Apr 2023

Bibliographical note

Funding Information:
This study was funded by Bayer AG and Orion Pharma.

Funding Information:
Writing and editorial support in the development of this manuscript was provided by Michelle McDermott, PharmD, and Lauren Gallagher RPh, PhD, of OPEN Health Communications, London, UK, with financial support from Bayer Healthcare. The authors retained full editorial control over the content of the manuscript and the decision to publish.

Publisher Copyright:
© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.


  • androgen-receptor antagonist
  • bowel symptoms
  • castration-resistant prostatic neoplasms
  • quality of life
  • urinary symptoms

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't


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