Darolutamide Approved in Europe for Nonmetastatic CRPC

The European Commission has approved darolutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer who are at high risk for developing metastatic disease.

Karim Fizazi, MD, PhD

The European Commission has approved darolutamide (Nubeqa) for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC) who are at high risk for developing metastatic disease.1

The approval is based on results from the phase III ARAMIS trial, in which darolutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS) compared with placebo plus ADT (HR, 0.41; 95% CI, 0.34-0.50;&#8239;P&#8239;<.0001).2,3 The median MFS was 40.4 months versus 18.4 months for darolutamide/ADT and placebo/ADT, respectively.

The opinion follows a recent announcement regarding results of a preplanned final OS analysis from ARAMIS, which showed that the darolutamide regimen led to a significant improvement in overall survival (OS) compared with placebo and ADT in patients with nonmetastatic CRPC.4 Full findings from the analysis will be presented at an upcoming medical meeting.

“As men with nmCRPC typically have no symptoms and are leading active lives, it is important to have treatment options that delay the progression of their cancer while minimizing the burdensome side effects of treatment, allowing them to maintain their lifestyle with little disruption. Darolutamide provides a welcome new option with a favorable safety profile that helps patients to stay on therapy and allows us to meet these treatment goals,” lead ARAMIS investigator Karim Fizazi, MD, PhD, professor of Medicine at the Institut Gustave Roussy, Villejuif, France, said in a press release.

In the double-blind, placebo-controlled, multicenter, phase III ARAMIS study, investigators evaluated the efficacy and safety of darolutamide in combination with ADT in 1509 patients with nonmetastatic CRPC who were receiving a concomitant gonadotropin-releasing hormone analog or had a bilateral orchiectomy. Patients were randomized 2:1 to receive 600 mg of oral darolutamide twice daily or placebo plus ADT. All patients had an ECOG performance status of 0 to 1. The primary endpoint was MFS, and key secondary endpoints were OS, time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first symptomatic skeletal event, and characterization of the safety and tolerability.

At the time of the final MFS analysis, OS data were immature, but data also showed a trend toward improved survival. The 3-year rates of OS were 83% in the darolutamide arm versus 73% with placebo, translating to a 29% reduction in the risk of death (HR, 0.71; 95% CI, 0.50-0.99,&#8239;P&#8239;= .0452), according to results of an interim OS analysis.

Additional ARAMIS findings showed that darolutamide also maintained quality of life and led to a 35% reduction in the risk of pain progression versus placebo in this patient population (HR, 0.65; 95% CI, 0.53-0.79;&#8239;P&#8239;<.0001).5 The AR inhibitor also led to a 57% reduction in the risk of symptomatic skeletal event development compared with placebo (HR, 0.43; 95% CI, 0.22-0.84;&#8239;P&#8239;= .011).

Regarding safety, adverse events (AEs) that occurred more frequently with the androgen receptor inhibitor versus placebo were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Moreover, data presented at the 2019 ESMO Asia Congress from the ARAMIS trial also showed that darolutamide delays disease progression and subsequent treatment for patients with nonmetastatic CRPC compared with placebo, while maintaining quality of life.6

The international, double-blind, placebo-controlled, phase III ARASENS study is exploring darolutamide plus ADT in combination with docetaxel in approximately 1300 patients with newly diagnosed, metastatic hormone-sensitive prostate cancer (NCT02799602).


  1. Nubeqa® (darolutamide) receives EU approval as a new treatment for men with non-metastatic castration-resistant prostate cancer. Published online March 30, 2020. https://yhoo.it/2WVpofC. Accessed March 30, 2020.
  2. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer.&#8239;N Eng J Med. 2019;380(13):1235-1246. doi: 10.1056/NEJMoa1815671.
  3. Fizazi K, Shore ND, Tammela T, et al. ARAMIS: efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC).&#8239;J Clin Oncol.&#8239;2019;37(suppl 7s; abstr 140). doi: 10.1200/JCO.2019.37.7_suppl.140.
  4. Nubeqa (darolutamide) plus androgen deprivation therapy achieved the secondary endpoint of overall survival (OS) in men with non-metastatic castration-resistant prostate cancer [news release]: Whippany, NJ. Bayer. Published January 30, 2020. https://bit.ly/3aTXBAD. Accessed January 30, 2020.
  5. Fizazi K, Shore ND Tammela T, et al. Impact of darolutamide (DARO) on pain and quality of life (QoL) in patients (Pts) with nonmetastatic castrate-resistant prostate cancer (nmCRPC).&#8239;J Clin Oncol. 2019;37(suppl 15; abstr 5000). doi: 10.1200/JCO.2019.37.15_suppl.5000.
  6. Pang J S-T, Shore N, Smith MR, et al. Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial.&#8239;Ann Oncol. 2019;30(suppl_9):mdz424.001. doi: 10.1093/annonc/mdz424.001.
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