Black patients have higher prostate cancer incidence and mortality rates compared with other racial groups. However, Black patients have often been underrepresented in pivotal prostate cancer trials, making subgroup analyses important for understanding treatment outcomes across patient populations.
A new analysis from the phase 3 ARANOTE trial evaluated the efficacy and safety of darolutamide plus androgen-deprivation therapy in Black patients with metastatic hormone-sensitive prostate cancer.
The brief communication, titled “Efficacy and safety of darolutamide plus androgen-deprivation therapy in Black patients with metastatic hormone-sensitive prostate cancer from the phase 3 ARANOTE trial,” was published in Prostate Cancer and Prostatic Diseases on June 20, 2026.
Authors: Quoc-Dien Trinh, Daniel J. George, Neal Shore, Egils Vjaters, David Olmos, Andrea Juliana P. de Santana Gomes, Augusto Cesar de Andrade Mota, Natasha Littleton, Shankar Srinivasan, Frank Verholen, Kunhi Parambath Haresh, and Fred Saad.
About ARANOTE
ARANOTE was a global phase 3 trial evaluating darolutamide plus androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer. Patients starting ADT were randomly assigned in a 2:1 ratio to receive darolutamide 600 mg twice daily or placebo, both given with ADT.
The primary endpoint was radiological progression-free survival. Secondary endpoints included time to metastatic castration-resistant prostate cancer, time to PSA progression, PSA response, time to initiation of subsequent anticancer therapy, time to pain progression, and safety.
Read more about Success Rate of Hormone Therapy for Prostate Cancer on OncoDaily.
What is Darolutamide?
Darolutamide is a nonsteroidal antiandrogen used to treat certain types of prostate cancer by blocking the effects of androgens, such as testosterone, which can fuel cancer growth.
It works by competitively binding to androgen receptors in prostate cancer cells and preventing androgens from activating these receptors. This blocks androgen receptor movement into the cell nucleus and reduces the activation of genes that promote tumor growth.
Darolutamide also produces an active metabolite, ketodarolutamide, which contributes to its therapeutic effect. Notably, darolutamide has limited penetration across the blood-brain barrier, which may reduce the risk of central nervous system side effects compared with some other antiandrogens.
By disrupting androgen receptor signaling, darolutamide helps slow the progression of prostate cancer, particularly in patients receiving androgen deprivation–based treatment.
Read more about Darolutamide (Nubeqa) on OncoDaily.
Black Patient Subgroup
Of the 669 patients enrolled in ARANOTE, 65 patients were self-reported Black. Among them, 41 received darolutamide plus ADT and 24 received placebo plus ADT. Black patients in the trial were enrolled from Brazil, South Africa, and Australia, with most patients from Brazil.
Baseline characteristics were generally similar between treatment groups. Compared with the overall ARANOTE population, Black patients had a higher median baseline PSA level and a higher proportion of high-volume metastatic hormone-sensitive prostate cancer.
Radiological Progression-Free Survival
In Black patients, darolutamide plus ADT reduced the risk of radiological progression or death by 49% compared with placebo plus ADT. The hazard ratio for radiological progression-free survival was 0.51, with a 95% confidence interval of 0.21 to 1.23. Median radiological progression-free survival was not reached in either treatment group.
The analysis reported 10 radiological progression-free survival events among 41 Black patients receiving darolutamide and 10 events among 24 Black patients receiving placebo.
Other Efficacy Outcomes
Darolutamide plus ADT was associated with delayed time to metastatic castration-resistant prostate cancer compared with placebo plus ADT. The hazard ratio for time to metastatic castration-resistant prostate cancer was 0.33, with a 95% confidence interval of 0.16 to 0.67.
Time to PSA progression was also delayed with darolutamide plus ADT, with a hazard ratio of 0.33 and a 95% confidence interval of 0.15 to 0.73. A PSA response below 0.2 ng/mL at any time was reported in 59.5% of Black patients receiving darolutamide compared with 18.2% of those receiving placebo.
Darolutamide was also associated with delayed time to initiation of subsequent anticancer therapy and time to pain progression compared with placebo, although confidence intervals were wide.
Safety
The safety profile of darolutamide plus ADT in Black patients was generally consistent with the overall ARANOTE population. Treatment-emergent adverse events were similar between treatment groups. Treatment-emergent adverse events leading to study-drug discontinuation occurred in 7.1% of patients receiving darolutamide and 4.3% of patients receiving placebo.
The most common treatment-emergent adverse events included hypertension, vasodilatation or flushing, diabetes mellitus, and hyperglycaemia. Fatigue was reported at low rates, occurring in 4.8% of patients receiving darolutamide and 8.7% of patients receiving placebo.
Study Limitations
This subgroup analysis was limited by the small number of Black patients and the limited number of events. Because of this, several confidence intervals were wide, including the confidence interval for radiological progression-free survival. The authors also noted the heterogeneity of the Black racial category enrolled in the trial, with most patients coming from Brazil.
Takeaway
In the Black patient subgroup of ARANOTE, darolutamide plus ADT was associated with improved radiological progression-free survival and delayed time to metastatic castration-resistant prostate cancer and PSA progression compared with placebo plus ADT.
The findings support the efficacy and tolerability profile of darolutamide plus ADT in Black patients with metastatic hormone-sensitive prostate cancer, while also highlighting the importance of broader representation in prostate cancer clinical trials.
The full article is available in Prostate Cancer and Prostatic Diseases.
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