General Information

Nubeqa (darolutamide) is an androgen receptor inhibitor.

Nubeqa is specifically indicated for the treatment of patients with non-metastatic castration resistant prostate cancer and for the treatment of metastatic hormone-sensitive prostate cancer. 

Nubeqa is supplied as a tablet for oral administration. The recommended dose of Nubeqa is 600 mg (two 300 mg film-coated tablets) taken orally, twice daily, equivalent to a total daily dose of 1200 mg. Swallow tablets whole with food. Patients receiving Nubeqa should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy. Advise patients to take any missed dose as soon as they remember prior to the next scheduled dose, and not to take two doses together to make up for a missed dose.

If a patient experiences a greater than or equal to Grade 3 toxicity or an intolerable adverse reaction, withhold dosing or reduce to 300 mg twice daily until symptoms improve. Then the treatment may be resumed at a dose of 600 mg twice daily. Dose reduction below 300 mg twice daily is not recommended. 

Mechanism of Action

Nubeqa (darolutamide) is an androgen receptor inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro (approximately 1% activity compared to AR). Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer. 

Side Effects

Adverse effects associated with the use of Nubeqa may include, but are not limited to, the following:

• fatigue
• pain in extremity
• rash

Clinical Trial Results

The FDA approval of Nubeqa was based on ARAMIS, a randomized, double-blind, placebo-controlled, multi-center study that enrolled 1,509 patients with nmCRPC who were being treated with androgen deprivation therapy (ADT) and were at high risk for developing metastatic disease. The patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide orally twice daily or placebo along with ADT. Data demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT. 

The FDA approval of Nubeqa for metastatic hormone-sensitive prostate cancer was based on results of the Phase III ARASENS trial that demonstrated a statistically significant increase in overall survival (OS), the trial’s primary endpoint, with a reduction in the risk of death by 32% for those treated with Nubeqa plus ADT and docetaxel compared to ADT and docetaxel. Treatment with Nubeqa plus ADT and docetaxel also resulted in a statistically significant delay in time to pain progression.