Darolutamide Approved by FDA for Metastatic Castration-Sensitive Prostate Cancer

Updated on Tuesday, June 3, 2025, at 4:15 PM.

The FDA has approved darolutamide (Nubeqa, Bayer Healthcare Pharmaceuticals Inc) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC), according to a news release from the agency.¹

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Significant Efficacy in Patients With mCSPC

Efficacy of darolutamide in patients with mCSPC was evaluated in the phase 3 ARANOTE study (NCT04736199), in which 669 patients were randomly assigned to receive darolutamide 600 mg twice daily or placebo. Investigators determined that darolutamide plus concomitant androgen-deprivation therapy (ADT) significantly improved the primary end point of radiological progression-free survival (rPFS) by reducing the risk of progression or death by 46% compared with placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P < .0001).^2,3

Benefits were consistent and significant across subgroups—importantly, including patients with high- and low-volume disease. Overall survival (OS) indications suggested benefit with darolutamide compared with placebo (HR, 0.81; 95% CI, 0.59-1.12), with clinical benefits demonstrated across all other secondary end points, such as delayed time to metastatic castration-resistant prostate cancer (HR, 0.40; 95% CI, 0.32-0.51) and time to pain progression (HR, 0.72; 95% CI, 0.54-0.96), according to the investigators.³

A novel androgen receptor pathway inhibitor (ARPI), darolutamide was designed with a unique structure to prevent brain penetration and reduce the risk of drug-drug interactions, according to Fred Saad, director of genitourinary oncology at the University of Montreal and lead investigator of the ARANOTE study, in an interview following his presentation at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary Symposium. Compared with other standard-of-care treatments for mCSPC, darolutamide has been shown to have little difference vs placebo regarding adverse event (AE) profiles, with no major heightening of AEs such as fatigue, Saad explained.⁴

“There is no question that the foundation of treatment for metastatic hormone-sensitive prostate cancer is ADT plus an ARPI, with darolutamide now being a key option,” Saad said.⁴

Darolutamide in Triplet Regimen Demonstrates Positive Overall Survival

Darolutamide was previously investigated in ARASENS (NCT02799602), an international phase 3 trial that assigned 1306 patients with mCSPC to receive the treatment or placebo, each in combination with ADT and docetaxel (Taxotere; Sanofi), with a primary end point of OS. After the data cutoff point for the primary analysis, investigators found a significantly lower risk of death (32.5%) in the darolutamide group compared with the placebo group (HR, 0.68; 95% CI, 0.57-0.80; P < .001).⁵

Further, darolutamide demonstrated consistent benefits across secondary end points—including time to pain progression, symptomatic skeletal event-free survival, and time to worsening of disease-related physical symptoms—and elicited similar rates of AEs vs placebo; however, the frequency of grade 3 or 4 AEs was higher for the darolutamide group than in the placebo group (66.1% vs 63.5%), with neutropenia being the most common AE across all patients.⁵

Patient Quality of Life and Future Research Avenues

Quality of life (QoL) is critical for patients with mCSPC undergoing intensive treatment with agents like darolutamide. Data from post hoc analyses of ARANOTE were recently presented at the 2025 ASCO Annual Meeting, demonstrating that darolutamide extended the time to deterioration in Functional Assessment of Cancer Therapy—Prostate total score by about 5.1 months compared with placebo, with a median of 16.6 months vs 11.5 months (HR, 0.76; 95% CI, 0.61-0.93).^6,7

Darolutamide was also associated with a longer time to deterioration in social and family well-being (HR, 0.79; 95% CI, 0.64-0.98), functional well-being (HR, 0.78; 95% CI, 0.63-0.96), and urinary symptoms (HR, 0.78; 95% CI, 0.61-0.99), all critical aspects of QoL for patients with mCSPC. Triplet regimens remain arduous and burdensome for patients, and many can experience resistance or untenable progression, “meaning there is more work to do,” according to Saad.^4,6,7

“Future strategies may involve quadruplet or even quintuple therapy to address resistance mechanisms,” Saad explained. “A better understanding of tumor biology will help determine whether a patient needs doublet, triplet, or intensified therapy.”⁴

REFERENCES

1. FDA. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News Release. Released June 3, 2025. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer?utm_medium=email&utm_source=govdelivery

2. ClinicalTrials.gov. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). National Library of Medicine. Last Updated April 27, 2025. Accessed June 3, 2025. https://clinicaltrials.gov/study/NCT04736199

3. Saad F, Vjaters E, Shore N, et al. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. J Clin Oncol. 2024;42(36):4271-4281. doi:10.1200/JCO-24-01798

4. Gerlach A. ASCO GU: ARANOTE and ARASENS trials reinforce darolutamide in metastatic hormone-sensitive prostate cancer. Pharmacy Times. Published February 26, 2025. Accessed June 3, 2025. https://www.pharmacytimes.com/view/asco-gu-aranote-and-arasens-trials-reinforce-darolutamide-in-metastatic-hormone-sensitive-prostate-cancer

5. ClinicalTrials.gov. Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (ARASENS). National Library of Medicine. Last Updated April 16, 2024. Accessed June 3, 2025. https://www.clinicaltrials.gov/study/NCT02799602

6. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132-1142. doi:10.1056/NEJMoa2119115

7. Bayer Pharmaceuticals. 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. Released May 27, 2025. Accessed June 3, 2025. https://www.bayer.com/en/us/news-stories/nubeqa-androgen-receptor-inhibitor