Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer.

ABSTRACT

Darolutamide (NUBEQA®) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).

Prostate cancer is the second and fourth most diagnosed cancer in the USA and Europe, respectively. Distant metastases are detected in 8% of patients at initial presentation and are associated with poorer 5-year survival rates in comparison to patients with localised or regional disease. Historically, patients with metastatic hormone-sensitive prostate cancer (mHSPC) were treated with androgen deprivation therapy (ADT). More recently, patients have been treated with ADT plus either docetaxel or an androgen receptor inhibitor (ARi), or with a combination of an ARi, ADT and docetaxel. Darolutamide (NUBEQA®) is an orally administered ARi which has been approved in combination with ADT and docetaxel for the treatment of mHSPC. In a clinical trial, darolutamide plus ADT and docetaxel was effective in prolonging the survival of patients in comparison with placebo plus ADT and docetaxel. Darolutamide plus ADT and docetaxel had a manageable tolerability profile and the adverse events reported with darolutamide plus ADT and docetaxel were consistent with those reported for ADT and docetaxel. Overall, darolutamide expands the availability of treatments for mHSPC and may be useful for patients with more severe disease.