Darolutamide Gains FDA Approval for Metastatic Castration-Sensitive Prostate Cancer

The FDA has approved darolutamide (Nubeqa; Bayer Healthcare Pharmaceuticals) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC), expanding its use beyond previously approved indications.¹ This approval is supported by data from the phase 3 ARANOTE trial (NCT04736199), which demonstrated a significant improvement in radiographic progression-free survival (rPFS) for patients treated with darolutamide in combination with androgen deprivation therapy (ADT) compared with those receiving placebo plus ADT.

Additionally, new post-hoc analyses from the ARANOTE trial presented the morning of the approval at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, reveal that treatment with darolutamide plus ADT significantly improves health-related quality of life (HRQOL) and delays pain progression in patients with mCSPC.²

"These results from the ARANOTE trial highlight the potential of darolutamide to not only extend radiographic progression-free survival for patients with metastatic castration-sensitive prostate cancer, but to do so while creating clinically meaningful delays in deterioration of quality of life compared to ADT alone," Alicia K. Morgans, MD, Dana-Farber Cancer Institute, Boston, said in a statement. "The ability to maintain social, family, and functional well-being, along with managing urinary symptoms and delaying pain progression, are important to patients with metastatic castration-sensitive prostate cancer."

In the ARANOTE study, patients receiving darolutamide (n = 446) did not reach median rPFS, while those on placebo (n = 223) had a median rPFS of 25.0 months (HR, 0.54; 95% CI, 0.41–0.71; P < .0001).³ At 24 months, 70.3% of darolutamide-treated patients were free of radiographic progression compared with 52.1% in the placebo group. The rPFS benefits of darolutamide were consistent across subgroups, including both high-volume and low-volume disease.

While overall survival (OS) did not reach statistical significance (HR, 0.78; 95% CI, 0.58–1.05), a favorable trend was observed, with 24-month OS rates of 79.8% for darolutamide vs 75.5% for placebo.

Secondary end points further underscored the clinical benefit of darolutamide. The drug significantly delayed time to metastatic castration-resistant prostate cancer (mCRPC; HR 0.40), PSA progression (HR, 0.31), and the need for subsequent systemic anticancer therapy (HR, 0.40). A higher proportion of patients treated with darolutamide also achieved deep PSA suppression, with 62.6% reaching levels below 0.2 ng/mL, compared with 18.5% in the placebo group. Darolutamide also showed a benefit in delaying time to pain progression (HR, 0.72).

The FDA has approved darolutamide for the treatment of patients with metastatic castration-sensitive prostate cancer.

image credit: wladimir1804 - stock.adobe.com

The safety profile of darolutamide remained consistent with previous data. The most common grade 3 or 4 adverse events included hypertension (3.6%), anemia (3.6%), and pain in extremities (1.8%), with relatively low incidences of serious adverse effects overall. The drug carries warnings for ischemic heart disease, seizure, and embryo-fetal toxicity. The approved dose is 600 mg per day, administered as 2 300-mg tablets taken orally twice daily with food.

With this approval, darolutamide offers a new option for men with mCSPC, a disease with limited long-term survival prospects. The ARANOTE data reinforce its value in improving disease control and delaying key markers of progression.

The review was conducted under Project Orbis, an international collaboration led by the FDA Oncology Center of Excellence that facilitates concurrent review of oncology drugs across partner countries. Regulatory agencies from Australia, Canada, Switzerland, and the United Kingdom participated in the review of darolutamide’s new indication, and evaluations are ongoing in those regions.¹

References

1. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. FDA.gov. June 3, 2025. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

2. ASCO 2025: phase III ARANOTE post-hoc analyses presented on health-related quality of life and pain outcomes in patients with metastatic castration-sensitive prostate cancer receiving Nubeqa (darolutamide) plus ADT. News release. Bayer. May 27, 2025. Accessed June 3, 2025. https://www.bayer.com/en/us/news-stories/nubeqa-androgen-receptor-inhibitor

3. Wahner A. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. OncLive^®. June 3, 2025. Accessed June 3, 2025. https://www.onclive.com/view/fda-approves-darolutamide-for-metastatic-castration-sensitive-prostate-cancer