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 - 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 -
