New Subgroup Analysis Confirms Efficacy and Safety of Darolutamide Across Different Subgroups of Patients with Metastatic Hormone-Sensitive Prostate Cancer

April 2023, Vol 14, No 2

An analysis from the ARASENS trial showed that the addition of darolutamide (Nubeqa) to androgen-deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in subgroups of patients with metastatic hormone-sensitive prostate cancer (mHSPC) with high-volume and high-risk disease and should be considered the new standard of care for this patient population. These findings were presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium by Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Division of Hematology Oncology, Department of Medicine, and Deputy Director, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, and published simultaneously in the Journal of Clinical Oncology.1

Study Details

ARASENS was a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial comparing darolutamide plus ADT and docetaxel versus ADT plus docetaxel alone in patients with mHSPC. A total of 1306 patients were randomized in a 1:1 ratio to darolutamide 600 mg twice daily or matching placebo, both in combination with ADT and docetaxel 75 mg/m2, for 6 cycles.

As reported previously, in the total population, darolutamide plus ADT in combination with docetaxel significantly reduced the risk for death in patients with mHSPC by 32.5% (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.57-0.80; P <.001) compared with ADT plus docetaxel alone.2 These results led to the FDA approval of darolutamide for use in combination with docetaxel for the treatment of patients with mHSPC in August 2022.

The analysis presented during the meeting assessed survival outcomes in subgroups with high-volume and high-risk disease. High-volume disease was defined as visceral metastases and/or 4 or more bone metastases with at least 1 beyond the vertebral column/pelvis. High-risk disease was defined as 2 or more risk factors from among Gleason score ≥8, 3 or more bone lesions, and presence of measurable visceral metastases.

Of the 1305 patients in the full analysis set, 1005 (77%) had high-volume disease, 912 (70%) had high-risk disease, 300 (23%) had low-volume disease, and 393 (30%) had low-risk disease.

Darolutamide plus ADT and docetaxel prolonged OS regardless of disease volume or risk. Median OS was not reached for patients with high-volume disease (HR, 0.69; 95% CI, 0.57-0.82) or low-volume disease (HR, 0.68; 95% CI, 0.41-1.13). Median OS was also not reached in both the high-risk disease subgroup (HR, 0.71; 95% CI, 0.58-0.86) and the low-risk disease subgroup (HR, 0.62; 95% CI, 0.42-0.90) with the darolutamide-based regimen.

In addition, the darolutamide group had prolonged time to castration resistance versus the control group among patients with high-volume disease (HR, 0.41; 95% CI, 0.34-0.49), low-volume disease (HR, 0.21; 95% CI, 0.14-0.33), high-risk disease (HR, 0.38; 95% CI, 0.32-0.46), and low-risk disease (HR, 0.32; 95% CI, 0.23-0.45).

The incidence of treatment-emergent adverse events across subgroups was consistent with the overall ARASENS population. Serious adverse events in patients in the darolutamide arm compared with those in the control group were 45.4% versus 43.5% for those with high-volume disease, 42.9% versus 38.2% for those with low-volume disease, 45.3% versus 42.9% for patients with high-risk disease, and 43.7% versus 40.9% for those with low-risk disease.

“The growing data from the ARASENS trial continues to demonstrate darolutamide’s value in treating patients with mHSPC. The benefit is especially in those with high-volume or high-risk disease. They also provide treating physicians with greater insight into the mHSPC patient population that may benefit from this therapy,” Dr Hussain said.


  1. Hussain M, Tombal B, Saad F, et al. Darolutamide plus androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer by disease volume and risk subgroups in the phase III ARASENS trial. J Clin Oncol. 2023;41:1-13.
  2. Smith M, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132-1142.

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