TY - JOUR
T1 - 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
AU - Hussain, Maha
AU - Tombal, Bertrand
AU - Saad, Fred
AU - Fizazi, Karim
AU - Sternberg, Cora N.
AU - Crawford, E. David
AU - Shore, Neal
AU - Kopyltsov, Evgeny
AU - Kalebasty, Arash Rezazadeh
AU - Bögemann, Martin
AU - Ye, Dingwei
AU - Cruz, Felipe
AU - Suzuki, Hiroyoshi
AU - Kapur, Shivani
AU - Srinivasan, Shankar
AU - Verholen, Frank
AU - Kuss, Iris
AU - Joensuu, Heikki
AU - Smith, Matthew R.
N1 - Funding Information:
Statistical analyses were provided by Kevin Clark, MS, MPH, PT, of Bayer and Lei Li, MSc, of CHRESTOS Concept GmbH & Co KG. 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.
Funding Information:
Supported by Bayer AG and Orion Pharma.
Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/7/10
Y1 - 2023/7/10
N2 - PURPOSEFor 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.METHODSPatients 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.RESULTSOf 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 castration-resistant 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.CONCLUSIONIn patients with high-volume and high-risk/low-risk metastatic hormone-sensitive 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.
AB - PURPOSEFor 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.METHODSPatients 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.RESULTSOf 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 castration-resistant 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.CONCLUSIONIn patients with high-volume and high-risk/low-risk metastatic hormone-sensitive 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.
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U2 - 10.1200/JCO.23.00041
DO - 10.1200/JCO.23.00041
M3 - Article
C2 - 36795843
AN - SCOPUS:85159302623
SN - 0732-183X
VL - 41
SP - 3595
EP - 3607
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -
