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

Author(s): Maha Hussain, MD1; Bertrand Tombal, MD, PhD2; Fred Saad, MD3; Karim Fizazi, MD, PhD4; Cora N. Sternberg, MD5; E. David Crawford, MD6; Neal Shore, MD7; Evgeny Kopyltsov, MD8; Arash Rezazadeh Kalebasty, MD9; Martin Bögemann, MD10; Dingwei Ye, MD11; Felipe Cruz, MD, PhD12; Hiroyoshi Suzuki, MD, PhD13; Shivani Kapur, MD14; Shankar Srinivasan, PhD15; Frank Verholen, MD16; Iris Kuss, MD17; Heikki Joensuu, MD18; and Matthew R. Smith, MD, PhD19
Source: DOI: 10.1200/JCO.23.00041 Journal of Clinical Oncology 41, no. 20 (July 10, 2023) 3595-3607.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

High burden prostate cancer patients benefit form androgen deprivation and Taxotere combination.


For patients with metastatic hormone-sensitive prostate cancer, metastatic burden affects outcome. We examined efficacy and safety from the ARASENS trial for subgroups by disease volume and risk.


Patients with metastatic hormone-sensitive prostate cancer were randomly assigned to darolutamide or placebo plus androgen-deprivation therapy and docetaxel. High-volume disease was defined as visceral metastases and/or ≥ 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis. High-risk disease was defined as ≥ 2 risk factors: Gleason score ≥ 8, ≥ 3 bone lesions, and presence of measurable visceral metastases.


Of 1,305 patients, 1,005 (77%) had high-volume disease and 912 (70%) had high-risk disease. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.82), high-risk (HR, 0.71; 95% CI, 0.58 to 0.86), and low-risk disease (HR, 0.62; 95% CI, 0.42 to 0.90), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide improved clinically relevant secondary end points of time to castrationresistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo in all disease volume and risk subgroups. Adverse events (AEs) were similar between treatment groups across subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide patients versus 64.2% of placebo patients in the high-volume subgroup and 70.1% versus 61.1% in the low-volume subgroup. Among the most common AEs, many were known toxicities related to docetaxel.


In patients with high-volume and high-risk/low-risk metastatic hormonesensitive prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel increased OS with a similar AE profile in the subgroups, consistent with the overall population.

Author Affiliations

1Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL; 2Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium; 3Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, Quebec, Canada; 4Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France; 5Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY; 6UC San Diego School of Medicine, San Diego, CA; 7Carolina Urologic Research Center/Genesis Care, Myrtle Beach, SC; 8Clinical Oncological Dispensary of Omsk Region, Omsk, Russian Federation; 9University of California Irvine, Division of Hematology/Oncology, Orange, CA; 10Department of Urology, Münster University Medical Center, Münster, Germany; 11Fudan University Shanghai Cancer Center, Xuhui District, Shanghai, China; 12Núcleo de Pesquisa e Ensino da Rede São Camilo, São Paulo, Brazil; 13Toho University Sakura Medical Center, Chiba, Japan; 14Bayer SEA, Singapore; 15Bayer HealthCare Pharmaceuticals Inc, Whippany, NJ; 16Bayer Consumer Care AG, Basel, Switzerland; 17Bayer AG, Berlin, Germany; 18Orion Corporation, Espoo, Finland; 19Massachusetts General Hospital Cancer Center, Boston, MA

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