New Reference: Darolutamide for Non-Metastatic Castration Resistant Prostate Cancer

In this phase 3 trial, darolutamide significantly prolonged metastasis-free survival in men with nonmetastatic, castration-resistant prostate cancer compared to placebo, reducing the risk of metastasis or death by 59%. Overall survival and progression-free survival were also improved with darolutamide. The incidence of adverse events was similar between the groups.

  • Study

    Randomized, double-blind, placebo-controlled, phase 3 trial [ARAMIS ClinicalTrials.gov number, NCT02200614]
    Men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of 10 months or less
    Darolutamide (n=955) vs placebo (n=554), continued on androgen-deprivation therapy



  • Efficacy

    mMFS: 40.4 mos vs 18.4 mos (HR 0.41 [0.34-0.50])
    OS favored darolutamide (HR 0.71 [0.50-0.99])
    Time to pain progression: 40.3 mos vs 25.4 mos (HR 0.65 [0.53-0.79])
    mPFS: 36.8 mos vs 14.8 mos (HR 0.38 [0.32-0.45])



  • Safety

    Grade >=3 AE occurred in 24.7% of darolutamide and 19.5% of placebo
    Serious AE in 24.8% with darolutamide and 20.0% with placebo
    Discontinuation due to AE: 8.9% with darolutamide vs 8.7% with placebo
    Fatigue (12.1% vs 8.7%), Back pain (8.8% vs 9.0%), Falls (4.2% vs 4.7%)
    Seizures: 0.2% vs 0.2%


  • N Engl J Med 2019;380:1235-46

    Fizazi K, Shore N, Tammela TL New Reference: Darolutamide for Non-Metastatic Castration Resistant Prostate Cancer

    http://doi.org/10.1056/NEJMoa1815671

    Reviewed by Ulas D. Bayraktar, MD on Nov 13, 2025

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