Darolutamide gets the OK in Europe for nmCRPC

Metastatic castration-resistant prostate cancer (mCRPC) has limited treatment options and metastatic growth is associated with increased comorbidities. To put the size of this group into context, metastases are present in over 84% of CRPC patients.1 Delaying CRPC progression at the M0 stage is highly sought after.

Enzalutamide and apalutamide, second-generation nonsteroidal antiandrogen agents (NSAAs), have been approved for the treatment of non-metastatic (nm)CRPC. Although both prolong metastasis-free survival (MFS), they are also associated with adverse events, such as seizures and fatigue, and hence a negative effect on patients’ quality of life (QoL).2,3

Darolutamide is another next-generation NSAA, although it has a distinct molecular structure compared to other agents in the same group. Data from the recent ARAMIS trial (NCT02200614) suggests that darolutamide may delay the onset of metastatic disease, as well as the associated pain for nmCRPC patients. Comparing the effects of darolutamide to those of a placebo in 1,509 patients with nmCRPC, the ARAMIS trial showed that darolutamide performed better in terms of MFS, which was the primary endpoint of the trial.4

Discussing the impact of the ARAMIS trial, Karim Fizazi, MD, PhD, of the University of Paris-Sud, Orsay, France, tells VJOncology at the 2019 Genitourinary Cancers Symposium, held in San Francisco, CA:

“The very good thing also of darolutamide, and we were really expecting that, is that the safety is just phenomenal. We actually don’t see an excess in CNS-related toxicity such as cognitive impairments, fatigue, seizures or these things. No excess in fractures or falls. No excess in cardiovascular problems. It is fully good for such a population of asymptomatic men”.5  

Darolutamide is structurally different from other NSAAs as it does not cross the blood-brain barrier.6 This results in lower toxicity levels than other similar drugs. Following this, the US Food and Drug Administration (FDA) approved darolutamide for the treatment of high-risk nmCRPC.7 The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) soon followed suit, approving darolutamide in January 2020 as a treatment for patients at high risk of developing metastatic disease.8

Darolutamide has demonstrated good efficacy and QoL in this patient population and may offer one avenue to shorten the unmet need in nmCRPC.

Written by Markiyan Mitchyn and Tom Southgate

Edited by Cally Cameron Smith


  1. Kirby M, Hirst C and Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011 Nov;65(11):1180-92.
  2. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.
  3. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
  4. Fizazi K, Shore ND, Tammela T, et al. ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC). Genitourinary Cancers Symposium 2019; 14-16 Feb; San Francisco, CA; J Clin Oncol; 2019. Abstract 140.
  5. VJOncology. GU Cancers 2019 | ARAMIS: efficacy and safety of darolutamide in nmCRPC. Available: https://www.vjoncology.com/video/vrl4r-okb6m-aramis-efficacy-and-safety-of-darolutamide-in-nmcrpc/. Last accessed 11/02/2020.
  6. Shore N, Zurth C, Fricke R, et al. Evaluation of Clinically Relevant Drug-Drug Interactions and Population Pharmacokinetics of Darolutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer: Results of Pre-Specified and Post Hoc Analyses of the Phase III ARAMIS Trial. Target Oncol. 2019 Oct;14(5):527-539.
  7. U.S. Food and Drug Administration (FDA). FDA approves darolutamide for non-metastatic castration-resistant prostate cancer (2019). Available: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer. Last accessed 07/02/2020.
  8. Orion Corporation. Positive CHMP opinion for darolutamide as a new treatment for men with non-metastatic castration-resistant prostate cancer (2020). Available: https://www.orion.fi/en/Orion-group/media/press-releases/2020/positive-chmp-opinion-for-darolutamide-as-a-new-treatment-for-men-with-non-metastatic-castration-resistant-prostate-cancer/. Last accessed 07/02/2020.