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.

Hussain, Maha;Tombal, Bertrand;Saad, Fred;Fizazi, Karim;Smith, Matthew R;et.al.
(2023) Journal of clinical oncology — Vol. 41, n° 20, p. 3595-3607 (2023)

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  • Hussain, Mahaorcid-logo
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  • Tombal, Bertrandorcid-logoUCLouvain
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  • Saad, Fredorcid-logo
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  • Fizazi, Karimorcid-logo
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  • Smith, Matthew R
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Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 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. CONCLUSION: In 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.[Media: see text]. TRIAL REGISTRATION: ClinicalTrials.gov NCT02799602.
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Hussain, M., Tombal, B., Saad, F., Fizazi, K., Sternberg, C. N., Crawford, E. D., Shore, N., Kopyltsov, E., Kalebasty, A. R., Bögemann, M., Ye, D., Cruz, F., Suzuki, H., Kapur, S., Srinivasan, S., Verholen, F., Kuss, I., Joensuu, H., & Smith, M. R. (2023). 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. Journal of clinical oncology, 41(20), 3595-3607. https://doi.org/10.1200/JCO.23.00041 (Original work published 2023)