Darolutamide/ADT Combo Delays Pain Progression and Enhances QOL in mHSPC

Alicia Morgans, MD, MPH

The addition of darolutamide (Nubeqa) to androgen deprivation therapy (ADT) offers patients with metastatic hormone-sensitive prostate cancer (mHSPC) a chance at less pain and better quality of life (QOL) compared with ADT alone, further underscoring the promise of this effective combination regimen, according to Alicia Morgans, MD, MPH.

Findings from an analysis of patient-reported outcomes (PROs) from the phase 3 ARANOTE trial (NCT04736199), which were presented at the 2025 ASCO Annual Meeting, showed that patients with mHSPC who received darolutamide plus ADT had greater improvements in health-related QOL (HRQOL) outcomes like delay in pain progression (stratified HR, 0.72; 95% CI, 0.54-0.96) and extension in median time to Functional Assessment of Cancer Therapy-Prostate (FACT-P) deterioration (HR, 0.76; 95% CI, 0.61-0.94) vs placebo plus ADT.1

Notably, on June 3, 2025, the FDA approved darolutamide for the treatment of patients with mHSPC based on findings from ARANOTE.2 Data that supported the approval showed that patients in the darolutamide/ADT arm (n = 446) achieved a significantly higher median radiographic progression-free survival (rPFS) vs those in the placebo/ADT arm (n = 223), at not reached (NR; 95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR; (HR, 0.54; 95% CI, 0.41-0.71; P < 0.0001).2,3

“The combination of ADT and darolutamide is an option that provides that cancer control with, from a patient’s perspective, improved QOL and a maintenance of pain control that’s improved compared with ADT and placebo,” Morgans said in an interview with OncLive® during ASCO 2025.

In the interview, Morgans discussed reasons for diving into HRQOL outcomes of the ARANOTE trial; key findings from this analysis; and how the combined efficacy, safety, and QOL outcomes with darolutamide plus ADT collectively support the use of this regimen in patients with mHSPC.

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

OncLive: What key efficacy findings have been previously presented from ARANOTE?

Morgans: The ARANOTE study randomly assigned patients with mHSPC to receive treatment with ADT and darolutamide vs ADT and placebo. This was an international study that was all performed outside of the United States. The primary end point of this study was to understand rPFS, with overall survival being a key secondary end point in the analysis. Of note, of the patients who enrolled, most had de novo metastatic disease and high-volume metastatic disease. The primary end point of rPFS was improved in patients who were treated with ADT and darolutamide, with a hazard ratio of 0.54 favoring that combination vs ADT and placebo, cementing the benefit of this combination in terms of cancer control mHSPC setting without chemotherapy.

What HRQOL outcomes from the trial were presented in this most recent analysis?

This was the QOL analysis that was built into this randomized trial to understand what the patient experience was. The piece that was presented at ASCO [2025] was the PRO data, including data from the Brief Pain Inventory–Short Form, as well as the FACT-P, which is an assessment of overall QOL. When we looked at the outcomes from these 2 analyses, we saw that time to pain deterioration—or worsening pain—was improved with ADT plus darolutamide vs ADT and placebo, and this had a hazard ratio of 0.72, favoring that combination arm. When we looked at the FACT-P, we saw that the combination is the only androgen receptor antagonist to improve QOL vs the control arm—ADT and placebo, with an improvement in median QOL duration of 5.1 months. Importantly, this combination shows both efficacy in terms of cancer control, but also this maintenance or improvement in QOL that is important for patients.

The other piece of data that was assessed within this dataset was whether the depth of prostate-specific antigen [PSA] response was also associated with QOL for patients. We saw that it was. If patients achieved a low or very low PSA of 0.2 or below, they had even better QOL responses. This shows us that a patient’s QOL and their cancer control are intimately mixed. When we control cancer better, when we get to that ultralow or low PSA, we’re getting better cancer control and probably maintaining [that control] for longer and helping to keep that QOL in a better place, too. That was another important analysis.

Within the context of the known efficacy and safety profile of darolutamide plus ADT, how might these QOL data influence clinical decision-making?

Oncologists and urologists who use these agents want to make sure they’re choosing medicines that are going to improve cancer control but are also going to be tolerable and bearable for patients. We already know that doublet therapies of ADT plus androgen receptor pathway inhibitors are going to be important for this patient population, and this is the first study to show that ADT and darolutamide without chemotherapy is [a treatment option for these patients]. [It also] provides data that this doublet, which we didn’t previously have, can be more effective than ADT alone. From a clinical perspective, this [QOL analysis] gives data [to support] the decision-making that clinicians have already been doing, which is dropping the chemotherapy and giving this doublet combination sometimes in clinic when they find that the patient cannot handle chemotherapy. We now have the evidence to show that we can maintain cancer control and maintain QOL when we do that.

What are the potential next steps for continuing to analyze the ARANOTE data?

Future steps are to understand if there were outliers on either end who had extreme QOL improvements or maybe didn’t, and understand whether there are clinical characteristics or other aspects of their cancer that might be associated with those responses at either extreme. We’re always trying to dig through the data to find and understand things better. That’s one place to start.

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. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. FDA. June 3, 2025. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer
3. Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42(36):4271-4281. doi:10.1200/JCO-24-01798