Darolutamide Plus ADT Confers HRQOL Benefits in Metastatic Hormone-Sensitive Prostate Cancer

Darolutamide Plus ADT in Metastatic Hormone-Sensitive

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The combination of darolutamide (Nubeqa) and androgen deprivation therapy (ADT) improved health-related quality of life (HRQOL) outcomes vs placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to data from an analysis of patient-reported outcomes (PROs) from the phase 3 ARANOTE trial (NCT04736199) that were presented at the 2025 ASCO Annual Meeting.¹

The analysis showed that treatment with darolutamide was associated with a delay in pain progression—defined as the time from randomization to a confirmed increase of at least 2 points in worst pain over the nadir or the initiation of opioid treatment for at least 7 days—vs placebo (stratified HR, 0.72; 95% CI, 0.54-0.96). When assessing time to pain progression by prostate-specific antigen (PSA) response, patients who reached a PSA level of less than 0.02 ng/mL at any time had a longer time to pain progression than patients with a PSA level greater than or equal to 0.2 ng/mL.

Darolutamide was associated with an extension in median time to Functional Assessment of Cancer Therapy-Prostate (FACT-P) deterioration—defined as the first decrease of 10 or more points in the total score—that was 5.1 months longer than placebo (HR, 0.76; 95% CI, 0.61-0.94). Improvements were most prominent in the areas of social and family well-being, functional well-being, and prostate cancer concerns, including urinary symptoms. Similarly, when assessing time to deterioration in FACT-P total score by PSA response, patients with a PSA level of less than 0.02 ng/mL at any time had a longer time to HRQOL deterioration vs those with a PSA level of 0.2 ng/mL or greater.

“[Darolutamide] is the first and only androgen receptor antagonist to demonstrate clinically meaningful delays in pain progression and overall well-being, including those specific areas of social and family well-being, functional well-being, and urinary symptoms. HRQOL benefits may be greatest in patients treated with darolutamide who had ultralow PSA levels,” Alicia Morgans, MD, MPH, stated in the presentation.

Morgans is a genitourinary medical oncologist and director of the Survivorship Program at Dana-Farber Cancer Center; as well as an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

In this analysis, multiple PRO measures were used to assess patient experience during treatment. These included the Brief Pain Inventory Short Form, which was used to assess worst pain in the past 24 hours; and the FACT-P total score. The FACT-P is a questionnaire evaluating overall QOL in patients with prostate cancer that includes domains like physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer–specific assessments, including bowel and urinary difficulties.

“[It is] critical…for us to recognize that our patients’ QOL, intuitively…is associated with disease control. But this is also helpful for us in clinical practice, so that we can encourage patients [that] as their cancer appears to be better controlled, we expect them to feel better,” Morgans explained during the presentation.

About the ARANOTE Trial

The ARANOTE trial assessed darolutamide plus ADT vs placebo and ADT for the treatment of patients with mHSPC. Findings from the study presented at the 2024 ESMO Congress showed that the darolutamide combination reduced the risk of radiographical progression or death by 46% vs placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P <.0001) and had a favorable safety profile.²

A total of 669 patients were enrolled globally and randomly assigned on a 2:1 basis to receive darolutamide at 600 mg twice daily plus ADT (n = 446) or placebo plus ADT (n = 223). The primary end point was radiographic progression-free survival (rPFS) by central blinded review, with secondary end points including overall survival, time to PSA progression, and safety.

At a data cutoff of June 7, 2024, the median follow-up was 25.3 months for the darolutamide group and 25.0 months for the placebo group. The median rPFS for darolutamide plus ADT was not reached (NR; 95% CI, NR-NR) compared with 25.0 months for placebo plus ADT (95% CI, 19.0-NR). At 24 months, the rate of rPFS was 70.3% for the darolutamide group vs 52.1% for the placebo group.

The median treatment duration was 24.2 months in the darolutamide group compared with 17.3 months for the placebo group. The incidence of treatment-emergent adverse events (TEAEs) was similar between the arms, at 91.0% for any-grade and 30.8% for grade 3/4 TEAEs with darolutamide plus ADT vs 90.0% for any-grade and 30.3% for grade 3/4 TEAEs with ADT plus placebo.

References

1. 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
2. Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Ann Oncol. 2024;35(suppl_2):1257-1258; doi:10.1016/j.annonc.2024.08.2311