Subgroup Data From ARANOTE Highlight rPFS Benefit of Darolutamide Plus ADT in Black Patients With mHSPC

Hormone-Sensitive Prostate Cancer
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Data from a subgroup analysis of the phase 3 ARANOTE trial (NCT04736199) demonstrate that darolutamide (Nubeqa) and androgen deprivation therapy (ADT) was associated with an improvement in radiographic progression-free survival (rPFS) and other efficacy end points vs placebo plus ADT in Black patients with metastatic hormone-sensitive prostate cancer/

Findings were presented at the 2025 American Urological Association Annual Meeting.

In ARANOTE, patients starting on ADT were randomly assigned 2:1 to receive darolutamide 600 mg daily or placebo. The primary end point was rPFS. Time to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, proportion of patients reaching a PSA level lower than 0.2 ng/mL at any time, time to initiation of subsequent anticancer therapy, and safety were secondary end points.

ARANOTE included 669 patients, of whom 65 were Black. Forty-one of these patients received darolutamide and 24 received placebo. The investigators reported that the baseline characteristics were “similar between treatment arms and generally consistent with the overall ARANOTE population, except Black patients had higher median baseline PSA levels (99.6 ng/mL vs 21.3 ng/mL) and a greater proportion had high-volume mHSPC (78.5% vs 70.6%),” the investigators wrote in their poster.

Quoc-Dien Trinh, MD, MBA

“With regards to our substudy that encompassed the Black population, it's very important to understand that we had about 10% of the ARANOTE population that self-identified as Black," lead study author Quoc-Dien Trinh, MD, MBA, said. "We know that representation of minorities in clinical trials is a problem in general, but specifically in the space of metastatic prostate cancer, so these results are definitely interesting. What we found was that Black patients do relatively well from an efficacy standpoint and from a safety standpoint with ADT plus darolutamide.” Trinh is the chair of urology at the University of Pittsburgh School of Medicine and chair of urology at the University of Pittsburgh in Pennsylvania.

The investigators reported that treatment with darolutamide reduced the risk of radiological progression or death by 49% in Black men. Regarding the primary end point of rPFS, the HR for Black patients was 0.51 compared with 0.57 in the overall ARANOTE cohort.

“[Regarding] PSA suppression to less than 0.2 ng/mL, we found that nearly 60% of Black men achieved suppression with ADT plus darolutamide vs less than 20% on the ADT alone arm, so a three-fold difference,” Trinh said.

Regarding safety, the investigators reported that treatment-emergent adverse event incidence was similar between the treatment groups for Black patients and was similar to what was seen in the overall ARANOTE population. In addition, the median duration of treatment in Black patients was 22.6 months in the darolutamide group vs 17.3 months in the placebo group.

Discussing the significance of the substudy, Trinh commented, “I think this is a very important study, but also a very important type of analysis to conduct, whether it's ARANOTE or any other study, which is to look at subpopulations; in this case, Black men. We know that Black men are more likely to develop prostate cancer, but also to die from prostate cancer. So it is very reassuring to know that in this subpopulation, the outcomes and the efficacy of this drug were certainly similar, and [there was] perhaps some signal that it could be even more beneficial. That, in itself, is very interesting. The other very important thing is that we know there is a lot of real-world evidence suggesting that underserved populations are less likely to get the latest therapies, sometimes more likely to get ADT alone, and sometimes the conversations and the things we may hear pertains to the fact that perhaps intensification leads to potentially more [adverse events], and assessing the safety of this drug in this population is very important, and the findings, again, were very reassuring. So the message to clinicians and to patients is that treatment intensification with darolutamide is certainly something that should be strongly considered in light of our substudy.”

Reference

Trinh Q-D, George DJ, Shore N, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy in Black patients with metastatic hormone-sensitive prostate cancer from the phase 3 ARANOTE trial. J Urol. 2025;213(5S):e578. doi:10.1097/01.JU.0001109908.15997.76.01