ASCO GU 2023: Efficacy and Safety of Darolutamide in Combination with ADT and Docetaxel by Disease Volume and Disease Risk in the Phase 3 ARASENS Study

( The 2023 GU ASCO annual meeting included a session on advanced prostate cancer, specifically new targets, new drugs, and new victories, featuring a presentation by Dr. Maha Hussain discussing efficacy and safety of darolutamide in combination with ADT and docetaxel by disease volume and disease risk in the phase 3 ARASENS study.

In ARASENS (NCT02799602), darolutamide plus ADT and docetaxel significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI: 0.57–0.80) vs placebo + ADT + docetaxel in patients with metastatic hormone-sensitive prostate cancer, with similar overall incidences of treatment-emergent adverse events between groups.1 The effect of darolutamide on overall survival was consistent across prespecified subgroups, including de novo and recurrent disease. For patients with metastatic hormone-sensitive prostate cancer, outcomes based on disease volume and risk provide additional information to clinicians. At the 2023 GU ASCO annual meeting, Dr. Hussain and colleagues presented a post-hoc analysis of the ARASENS study reporting the impact of disease burden and risk on efficacy and safety outcomes.

Patients with metastatic hormone-sensitive prostate cancer were randomized 1:1 to darolutamide 600 mg twice daily or placebo, with ADT + docetaxel. The trial design of ARASENS is as follows: 

Arasens study design.jpg

High-volume disease was defined as visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis (CHAARTED criteria). High-risk disease was defined as ≥2 risk factors:

  • Gleason score ≥8
  • ≥3 bone lesions
  • Presence of measurable visceral metastasis (LATITUDE criteria)

chaarted and latitude.jpg

Overall survival for these subgroups was assessed using an unstratified Cox regression model.

 Of 1,305 patients in the full analysis set, 1,005 (77%) had high-volume disease, 912 (70%) had high-risk disease, 300 (23%) had low-volume disease, and 393 (30%) had low-risk disease. As follows is a table summarizing select baseline demographics and disease characteristics by disease volume:

high volume vs low volume table.jpg

And by disease risk:

disease risk table.jpg

Darolutamide + ADT + docetaxel prolonged overall survival regardless of high- or low-volume disease. Specifically, for high volume mHSPC (HR 0.69, 95% CI 0.57-0.82) and low volume mHSPC (HR 0.68, 95% CI 0.41-1.13):

line graph 1.jpg

And for high-risk mHSPC (HR 0.71, 95% CI 0.58-0.86) and low-risk mHSPC (HR 0.62, 95% CI 0.42-0.90):

risk line graph.jpg

Both high and low volume, and high and low risk disease, benefited from triplet therapy with regards to time to castration-resistant prostate cancer:

volume line.jpg

Darolutamide improved clinically relevant secondary endpoints vs placebo in high/low-volume and risk subgroups, with HRs generally in the range of those observed in the overall population:


Incidences of treatment-emergent adverse events were consistent with the overall ARASENS population across subgroups by high/low volume and high/low risk: 

Dr. Hussain concluded her presentation discussing efficacy and safety of darolutamide in combination with ADT and docetaxel by disease volume and disease risk in ARASENS with the following take-home messages:

  • In patients with metastatic hormone-sensitive prostate cancer, the benefits of early treatment intensification with darolutamide + ADT + docetaxel on overall survival and key patient-relevant secondary efficacy endpoints vs placebo + ADT + docetaxel were similar in patients with high- and low-volume as well as high- and low-risk metastatic hormone-sensitive prostate cancer
  • The favorable safety profile of darolutamide was reconfirmed in high/low-volume and high/low-risk populations
  • Darolutamide + ADT + docetaxel sets a new standard of care for patients with metastatic hormone-sensitive prostate cancer

Presented by: Maha H. A. Hussain, MD, FACP, FASCO, Northwestern University, Feinberg School of Medicine, Chicago, IL

Co-Authors: Bertrand F. Tombal, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Neal D. Shore, Evgeny Kopyltsov, Arash Rezazadeh, Martin Boegemann, Ding-Wei Ye, Felipe Melo Cruz, Hiroyoshi Suzuki, Shivani Kapur, Shankar Srinivasan, Frank Verholen, Iris Kuss, Heikki Joensuu, Matthew Raymond Smith

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.


  1. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. 
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