FDA Approves Darolutamide in Metastatic Castration-Sensitive Prostate Cancer
Darolutamide is now an FDA-approved treatment option alone or in combination with docetaxel for metastatic castration-sensitive prostate cancer.
US FDA
- The FDA has approved darolutamide (Nubeqa) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC).
- The approval is supported by the phase 3 ARANOTE trial (NCT02799602).
- The ARASENS trial (NCT02799602) previously supported the approval of darolutamide plus docetaxel.
The FDA approved darolutamide (Nubeqa) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC).1 This approval expands the utility of darolutamide, which was previously approved for use in combination with docetaxel for mCSPC.2
The latest approval is based on data from the ARANOTE trial, a randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of darolutamide in 669 patients with mCSPC.1All participants in the trial received androgen deprivation therapy (ADT) or had undergone prior bilateral orchiectomy.
The primary efficacy endpoint for the ARANOTE trial was radiographic progression-free survival (rPFS), as assessed by blinded independent central review. Findings were presented at the 2024 European Society of Medical Oncology (ESMO) Congress. The study demonstrated a statistically significant improvement in rPFS for patients treated with darolutamide and ADT compared with those receiving placebo. The median rPFS was not reached (NR) in the darolutamide arm compared with 25 months (95% CI, 19-NR) in the placebo arm. This translates to a hazard ratio (HR) of 0.54 (95% CI: 0.41, 0.71; P <.0001), indicating a substantial reduction in the risk of radiographic progression or death for patients on darolutamide.
Prostate cancer under the microscope: © heitipaves - stock.adobe.com
Overall survival (OS) was a key secondary end point. At the time of the final analysis, the study did not show a statistically significant improvement in OS with darolutamide monotherapy (HR 0.78; 95% CI, 0.58-1.05), suggesting that while darolutamide significantly delays radiographic progression, its impact on OS in this setting requires further investigation or longer follow-up.
The safety profile of darolutamide as a single agent in the ARANOTE trial was consistent with previous findings from studies where it was used in combination.
The recommended dosage for darolutamide in this approved indication is 600 mg (2300 mg tablets) taken orally, twice daily, with food. Treatment is to be continued until disease progression or the onset of unacceptable toxicity.
The expanded approval of darolutamideprovides an additional treatment option for patients with mCSPC, offering a new approach that significantly delays radiographic progression. This development may influence treatment paradigms for this patient population, providing clinicians with more flexibility in tailoring therapeutic strategies.
Health-related quality of life outcomes from the ARANOTE trial were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on June 3, 2025.3 Here, darolutamide was associated with a delay in pain progression and deterioration in quality of life compared with placebo in this patient population.
“[This] is the first and only androgen receptor antagonist to demonstrate clinically meaningful delays in pain progression and overall well-being, including those specific areas of social and family well-being, functional well-being, and urinary symptoms. Health-related quality of life benefits may be greatest in patients treated with darolutamide who had ultralow [prostate-specific antigen (PSA)] levels,” said Alicia Morgans, MD, MPH, genitourinary medical oncologist and director of the Survivorship Program at Dana-Farber Cancer Center and associate professor of medicine at Harvard Medical School, in a presentation of the study.
