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ABSTRACT
Introduction: Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients.
Areas covered: The unmet clinical need, pharmacokinetics, preclinical development, and clinical efficacy and safety of darolutamide for the treatment of advanced prostate cancer are reviewed. The design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in men with non-metastatic CRPC and metastatic HSPC, respectively, are also discussed.
Expert opinion: Darolutamide is an oral, investigational, high-affinity AR antagonist which has activity against known AR mutants that confer resistance to other second-generation antiandrogens, has minimal blood–brain barrier penetration, and does not significantly increase serum testosterone. These features may offer potential advantages over the second-generation antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated promising antitumor activity and a favorable safety profile in men with metastatic CRPC.
Declaration of interest
N D Shore has received payment for consultancy and/or advisory roles from Amgen, Astellas, Bayer, Dendreon, Ferring, Janssen, Medivation, Inovio Pharmaceuticals and Sanofi; and honoraria for speakers’ bureau participation from Janssen, Bayer and Dendreon. Medical writing support, provided by Yvonne E Yarker, PhD, PAREXEL (Hackensack, NJ, USA) and Sabby Muneer, PhD, PAREXEL (Hackensack, NJ, USA), was utilized in the production of this manuscript and funded by Bayer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.