Darolutamide Offers Unique QOL Advantage Among AR Inhibitors in mHSPC

While androgen receptor (AR) inhibitors have long been a cornerstone in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), the ARANOTE trial (NCT04736199) sets darolutamide (Nubeqa) apart from the rest, especially in terms of its impact on patient quality of life.

Historically, AR inhibitors have demonstrated good tolerability, with many patients maintaining their overall well-being throughout treatment.

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 explains, “Patients can do well and can feel well during treatment, which is something I always encourage my patients.” However, what distinguishes darolutamide in the ARANOTE study is its ability not just to maintain, but to delay deterioration in pain and overall quality of life, a benefit not previously seen in other AR inhibitor trials.”

In prior studies of AR inhibitors, the addition of the therapy to ADT typically helped patients sustain their current quality of life. But as Morgans notes, they “didn’t delay the time until things get worse more so than ADT alone.” In contrast, the darolutamide and ADT combination showed a meaningful delay in pain progression and a longer time to decline in overall well-being, suggesting that this therapy may actually prolong good quality of life, not just preserve it.

Another key insight from the ARANOTE trial was the correlation between deeper prostate specific antigen (PSA) responses, a marker of stronger cancer control, and better patient-reported outcomes. Patients who experienced more profound declines in PSA also saw longer delays in pain worsening and overall quality-of-life deterioration. This reinforces the clinical message that better disease control can translate into better daily functioning and comfort, a dual benefit that both clinicians and patients value highly.

REFERENCE:

Morgans A, Haresh KP, Jievalta M, et al. Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial. J Clin Oncol. 2025;43(suppl 16):abstr 5004. doi:10.1200/JCO.2025.43.16_suppl.5004