Will darolutamide in double combination become the new standard of treatment for hormone-sensitive prostate cancer?

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Abstract

Darolutamide is a high-affinity second–generation antiandrogen, the effectiveness and favorable safety profile of which have been proven two phase III randomized clinical trials (RCTs) in metastatic hormone-sensitive prostate cancer (mHSPC) as part of a triple combination with docetaxel and androgen deprivation therapy (ADT) (ARASENS), as well as non-metastatic castration-resistant prostate cancer in the composition double combination with ADT (ARAMIS).

Positive results have now become available from another phase III RCT ARANOTE, aimed at comparing the efficacy of the double combination of darolutamide with ADT and placebo with ADT in patients with mHSPC. Darolutamide significantly prolonged radiological progression-free survival, reducing the risk of radiological progression or death by 46 % compared with placebo (primary endpoint), also provided benefit of secondary study endpoints, including time to castration resistance and time to pain progression. The clinical benefit of darolutamide in primary and secondary points was realized regardless of the volume of metastatic load. Data on overall survival is immature. The incidence of adverse events was low and similar in the darolutamide and placebo groups, with a lower incidence of fatigue in the darolutamide group. The obtained data on the effectiveness of darolutamide with ADT in mHSPC are comparable with the results of similar studies of other second-generation antiandrogens enzalutamide (ARCHES phase III RCT) and apalutamide (TITAN phase III RCT).

Potentially, the combination of ADT with darolutamide could claim a place in the list of standard treatment methods and expand therapeutic options for patients with mHSPC.

About the authors

Mariya I. Volkova

Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia

Author for correspondence.
Email: mivolkova@rambler.ru
ORCID iD: 0000-0001-7754-6624

Oncology Center No. 1, Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department

Russian Federation, Build. 7, 18A Zagorodnoe Shosse, Moscow 117152; Build. 1, 2 / 1 Barrikadnaya St., Moscow 125993

K. A. Turupaev

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: mivolkova@rambler.ru
ORCID iD: 0000-0001-8887-5108
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

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Copyright (c) 2026 Volkova M.I., Turupaev K.A.

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