Nubeqa Combo Positively Impacts HRQoL vs Placebo in Prostate Cancer Subgroup

Among patients with with metastatic hormone-sensitive prostate cancer (mHSPC), Nubeqa (darolutamide) and androgen deprivation therapy (ADT) treatment led to positive impacts on health-related quality of life (HRQoL) when compared with placebo and ADT, according to patient-reported outcome data from the phase 3 ARANOTE trial.

Notably, these data, which were shared at the 2025 ASCO Annual Meeting, also highlighted clinically meaningful delays in pain progression with the investigative treatment.

Furthermore, on June 3rd, 2025, just days after the data was presented at the meeting, the United States Food and Drug Administration (FDA) granted approval to Nubeqa for the treatment of patients with mHSPC based on data from the ARANOTE study.

“[This] 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. Health-related quality of life benefits may be greatest in patients treated with Nubeqa who had ultralow [prostate-specific antigen (PSA)] levels,” explained Dr. Alicia Morgans, in a presentation of the study

Morgans, a genitourinary medical oncologist who serves as the director of the Survivorship Program at Dana-Farber Cancer Center and associate professor of Medicine at Harvard Medical School, in Boston.

In this analysis, multiple patient-reported outcome measures were used to assess patient experience during treatment. They included the Brief Pain Inventory Short Form (BPI-SF), used to assess pain, specifically the worst pain in the past 24 hours, and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, a questionnaire evaluating overall quality of life in patients with prostate cancer. The FACT-P includes domains such as physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer-specific assessments, including bowel and urinary difficulties.

The analysis showed that Nubeqa 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 versus placebo. When assessing time to pain progression by PSA response, patients who reached a PSA of less than 0.02 or 0.2 nanograms per millilitre (ng/mL) at any time had a longer time to pain progression than patients with a PSA greater than or equal to 0.2 ng/mL.

“I think this is a critical thing for us to recognize that our patients’ quality of life, intuitively, of course, is associated with disease control. But this is also helpful for us in clinical practice so that we can encourage patients as their cancer appears to be better controlled; we expect them to feel better,” Morgans explained during the presentation.

Regarding time to FACT-P deterioration, Nubeqa was associated with an extension in median time to deterioration, defined as the first decrease of 10 or more points in the total score, by 5.1 months versus placebo. Improvements were most prominent in the areas of social and family well-being, functional well-being, and prostate cancer concerns, including urinary symptoms. Similarly with the BPI-SF, patients with a PSA of 0.02 or 0.2 ng/mL at any time had a longer time to HRQoL deterioration versus a PSA of 0.2 ng/mL or greater.

About the ARANOTE Trial

The phase 3 ARANOTE trial assessed Nubeqa plus ADT versus placebo and ADT for the treatment of mHSPC. Findings from the study presented at the 2024 European Society of Medical Oncology (ESMO) Congress showed that the combination reduced the risk of radiographical progression or death by 46% and demonstrated a favorable safety profile.

Following this data read-out, the FDA accepted a new drug application for the study combination in patients with mHSPC in November, 2024.

In February 2025, investigators also presented positive data from the trial at the 2025 ASCO Genitourinary Cancers Symposium.

A total of 669 patients enrolled globally were randomly assigned on a 2:1 basis to receive Nubeqa 600 mg twice daily plus ADT (446 patients) or placebo plus ADT (223 patients). The primary end point was radiographic progression-free survival 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 Nubeqa group and 25.0 months for the placebo group. The median radiographic progression-free survival for Nubeqa plus ADT was not reached compared with 25.0 months for placebo plus. At 24 months, the rate of radiographic progression-free survival was 70.3% for the Nubeqa group versus 52.1% for the placebo group.

The median treatment duration was 24.2 months in the Nubeqa group compared with 17.3 months for the placebo group. Incidence of treatment-emergent side effects was similar between the arms, with 91.0% any-grade and 30.8% grade 3 (severe) or 4 (life-threatening) treatment-emergent side effects with Nubeqa plus ADT and 90.0% any-grade and 30.3% grade 3 or 4 with ADT plus placebo.

Reference

“Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial” by Dr. Moregans, et al. Journal of Clinical Oncology.

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