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Efficacy and safety outcomes from ARASENS in patients with metastatic hormone-sensitive prostate cancer by disease volume and disease risk

In order to determine if specific subgroups of patients by disease volume or risk would achieve greater benefit from the combination of darolutamide, androgen-deprivation therapy and docetaxel (DARO + ADT + DOC), post-hoc subgroup analyses from the ARASENS study were conducted. In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment intensification with DARO + ADT + DOC increased overall survival with a similar adverse events profile in the subgroups, consistent with the overall population.

In ARASENS, darolutamide plus androgen-deprivation therapy (ADT) plus docetaxel significantly improved survival (HR[95%CI]: 0.68[0.57-0.80], p< 0.0001) vs. ADT plus docetaxel plus placebo in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The incidence of treatment-emergent adverse events (TEAEs) was similar between groups. In patients with mHSPC, disease burden is a prognostic factor. At ASCO GU 2023, Dr. Hussain presented a post-hoc analysis of the ARASENS study reporting the impact of disease burden and risk on efficacy and safety outcomes.

Study design

ARASENS is a randomised, placebo-controlled, phase III clinical trial in which patients with mHSPC were randomised (1:1) to darolutamide (DARO) 600 mg twice daily or placebo, with ADT plus docetaxel (DOC). 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, and presence of measurable visceral metastasis (LATITUDE criteria). OS for these subgroups was assessed using an unstratified Cox regression model.


Of the 1,305 patients in the ARASENS full analysis set, 77% had high-volume disease and 23% had low-volume disease. Furthermore, 70% had high-risk disease and 30% had low-risk disease. The vast majority of patients has de novo metastatic disease at initial diagnosis. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (HR[95%CI]: 0.69[0.57-0.82]), high-risk (HR[95%CI]: 0.71[0.58-0.86]), and low-risk disease (HR[95%CI]: 0.62[0.42-0.90]), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR[95%CI]: 0.68[0.41-1.13]).  With regard to the time to castration-resistant progression, the triplet therapy, irrespective of the volume of disease, had a much better hazard ratio (HR 0.41 for high-volume disease and HR 0.21 for low-volume disease). Also for the time to castration-resistance in the subsets of high- vs. low-risk patients, there is a significant reduction in the risk of death and the hazard ratio strongly favoured the triplet regimen (HR 0.38 for high-risk disease and HR 0.32 for low-risk disease). In addition, for other secondary endpoints, including time to pain progression, time to first symptomatic skeletal-related event, and time to initiation of subsequent systemic antineoplastic therapy, the triplet regimen had a better outcome, irrespective of the risk criteria or volume of disease. Finally, incidences of TEAEs were consistent with the overall ARASENS population across subgroups by high/low volume and high/low risk.


The combination of DARO + ADT + DOC improved overall survival and the risk of death was reduced by approximately 30% across volume and risk subgroups. Median OS was not reached in the DARO group, regardless of volume or risk. In addition, DARO + ADT + DOC improved key clinically relevant secondary efficacy endpoints across all subgroups.  Finally, the favourable safety profile of darolutamide was confirmed in all volume and risk subgroup populations, consistent with the overall ARASENS population. Therefore, darolutamide with ADT and docetaxel should be considered a new standard of care for patients with mHSPC.


Hussain M, et al. Efficacy and safety of darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) by disease volume and disease risk in the phase 3 ARASENS study. Presented at ASCO GU 2023; Abstract 15.

Speaker Maha Hussain

Maha Hussain

Maha Hussain, MD, FACP, FASCO, Northwestern University, Feinberg School of Medicine, Chicago, IL


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