Therapeutics: darolutamide for prostate cancer

Published: 16-Jan-2019

Prostate cancer is the second most commonly diagnosed cancer in men and leads to the fifth highest number of male cancer deaths

The risk increases with age and it largely affects those older than 50. Treatment mainly relies on surgery, radiotherapy and antiandrogen therapy, but resistance to hormone therapy frequently develops. A short doubling time for prostate specific antigen (PSA) is associated with a reduced time to first metastasis and death.

The prostate cancer is deemed to be castration-resistant if the disease continues to progress even when the amount of testosterone has been reduced to extremely low levels.

Treatment options for prostate cancer when PSA levels continue to rise despite antiandrogen therapy are limited. An alternative androgen receptor antagonist, the non-steroidal compound darolutamide, was invented by Orion and is being developed by Bayer.1

In the Phase I part of a Phase I/II trial, 24 patients with castration-resistant prostate cancer were given daily doses of 200–1800 mg of the drug; then, in Phase II, they were given 200, 400 or 1400 mg.2

No dose-limiting toxic effects were seen. In the Phase II part, 14 patients from Phase I continued, along with 110 new patients, and were given 200, 400 or 1400 mg doses. The most common treatment-emergent adverse events were fatigue, asthenia, hot flushes and decreased appetite. About a third of patients experienced a prostate specific antigen response.

Early results of a Phase III trial were reported in October 2018 via press release and the trial met its primary endpoint, with metastasis-free survival being significantly extended compared with the placebo.

Safety and tolerability were consistent with previously published data on the drug. In the trial, more than 1500 patients who were already receiving androgen deprivation therapy whose disease was not metastatic, but who were at risk of developing metastatic disease, were randomised to receive 600 mg of darolutamide twice a day or a matching placebo.

The primary endpoint was metastasis-free survival, with the secondary objectives being overall survival, time to first symptomatic skeletal event, time to initiation of the first cytotoxic chemotherapy, time to pain progression and characterisation of the safety and tolerability of the drug. The company plans to present the full data from the trial at an upcoming scientific meeting.


  1. A.M. Moilanen, et al., Sci. Rep. 5, 12007 (2015).
  2. K. Fizazi, et al., Lancet Oncol. 15, 975 (2014).

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