Nurse Role Is Key in Educating Patients on Benefit of Darolutamide Plus ADT in mHSPC

While the addition of darolutamide (Nubeqa) to androgen deprivation therapy (ADT) proved clinically beneficial among patients with metastatic hormone-sensitive prostate cancer (mHSPC), the nurse’s role in educating patients on its effect and its safety is key, according to Brenda Martone, RN, APP.¹

ARANOTE data underscore that combining darolutamide with ADT benefits patients with mHSPC irrespective of whether they also receive docetaxel.

At the 50th Annual Oncology Nursing Society Congress, safety and efficacy data from the phase 3 ARANOTE study (NCT04736199) were shared with oncology nurses so that they can better educate and counsel patients being treated with this approach. The data, which were shared in a poster and previously presented,² underscored that the darolutamide combination (n = 446) resulted in a 46% reduction in the risk of radiological progression or death vs placebo and ADT (n = 223). The median radiological progression-free survival (rPFS) in these respective arms was not reached (NR; 95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR), respectively (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The 24-month rPFS rate was 70.3% with darolutamide vs 52.1% without it.

A positive trend in overall survival (OS) was also observed, with darolutamide plus ADT leading to a 19% reduction in the risk of death vs ADT alone (HR, 0.81; 95% CI, 0.59-1.12). Moreover, the darolutamide combination led to a 60% reduction in risk of progression to metastatic castration-resistant prostate cancer (mCRPC); the median time to mCRPC in these respective arms was NR (95% CI, NR-NR) and 13.8 months (95% CI, 12.0-16.8; HR, 0.40; 95% CI, 0.32-0.51).

A higher proportion of patients in the darolutamide arm achieved undetectable PSA, defined as less than 0.2 ng/mL, vs those in the placebo arm, at 62.6% and 18.5%, respectively. The addition of darolutamide to ADT also delayed time to PSA progression, leading to a 69% reduction in the risk of PSA progression. The median time to PSA progression in the darolutamide arm was NR (95% CI, NR-NR) vs 16.8 months 95% CI, 13.9-20.1) in the placebo arm (HR, 0.31; 95% CI, 0.23-0.41).

Lastly, darolutamide demonstrated clear benefits over placebo in terms of time to pain progression, an important patient-relevant end point. The median time to pain progression was NR (95% CI, NR-NR) with darolutamide vs 29.9 months (95% CI, 29.7-NR) without, translating to a 28% reduction in the risk of pain progression (HR, 0.72; 95% CI, 0.54-0.96).

“When discussing treatment options with patients, it is important to consider efficacy, safety, and the impact of treatment on patients’ quality of life [QOL], [and] nurses play an important role in providing education to help patients manage disease symptoms and treatment [adverse] effects,”Martone, of Northwestern University, Feinberg School of Medicine, in Chicago, Illinois, and colleagues, wrote in a poster of the data.¹ “Together with the positive results of the [phase 3] ARASENS study [NCT02799602], the findings from ARANOTE provide the option to select treatment in mHSPC with and without docetaxel to meet patients’ individual needs and preferences.”

About ARANOTE: Design, Treatment, Objectives, Patient Population

The double-blind, placebo-controlled, global, phase 3 trial enrolled patients with mHSPC who had an ECOG performance status ranging from 0 to 2. Between March 2021 and August 2022, participants were randomly assigned 2:1 to receive darolutamide at 600 mg twice daily plus ADT vs placebo plus ADT. They were stratified by presence of visceral metastases (yes vs no) and receipt of prior local therapy (yes vs no).

The primary end point of the study was rPFS by blinded central review. Secondary end points comprised OS, time to initiation of subsequent anticancer therapy, time to mCRPC, time to PSA progression, undetectable PSA rates, time to pain progression, and safety.

“Demographic and baseline characteristics were well balanced between groups with global representation,” the authors noted. The median age of patients across the darolutamide and placebo arms was 70 years (range, 43-93). Most patients were White (56.3%; 56.1%), had de novo disease at initial diagnosis (71.1%; 75.3%), high disease volume (70.6%; 70.4%), and had a Gleason score of at least 8 (69.7%; 65.5%), but did not have visceral metastases (88.1%; 87.9%) and had not previously received local therapy (82.1%; 82.1%).

In terms of ECOG performance status, 52.7% of those in the darolutamide arm had a status of 0, 44.6% had a status of 1, and 2.7% had a status of 2; in the placebo arm, these respective rates were 43.9%, 52.5%, and 3.6%. The median serum PSA in the darolutamide arm was 21.4 ng/mL (range, 0.02-15,915) vs 21.2 ng/mL (range, 0.02-8533) in the placebo arm.

At the time of the data cutoff date of June 7, 2024, more patients on the darolutamide arm were still receiving treatment vs those on the placebo arm, at 53.8% and 28.3%, respectively.

In November 2024, the FDA accepted a supplemental new drug application seeking the approval of darolutamide plus ADT for use in patients with mHSPC based on ARANOTE data.³

Safety Spotlight

The incidence of adverse effects (AEs) was reported to be low and comparable between the treatment arms.¹ Any AEs were experienced by 91.0% of those in the darolutamide arm vs 90.0% of those in the placebo arm; grade 3 or 4 AEs were experienced by 30.8% and 30.3% of patients, respectively. Moreover, serious AEs were reported in 23.6% of those who received darolutamide plus ADT vs 23.5% of those who only received ADT.

Notably, a smaller proportion of patients in the darolutamide arm experienced AEs that led to treatment discontinuation vs those in the placebo arm, at 6.1% vs 9.0%, respectively. Authors underscored that this is a “measure of drug tolerability.”

Moreover, the incidence of AEs linked with androgen receptor inhibitor therapy was low in both arms. AEs included hypertension (darolutamide, 9.4%; placebo, 9.5%), vasodilation or flushing (9.2%; 7.2%), diabetes or hyperglycemia (9.0%; 9.5%), cardiac arrhythmias (8.8%; 6.8%), fatigue (5.6%; 8.1%), rash (4.3%; 3.6%), bone fracture (4.0%; 2.3%), coronary artery disorders (3.6%; 1.4%), mental impairment (1.6%; 0.5%), falls (1.3%; 0.9%), and heart failure (0.9%; 0.9%).

“The incidence of fatigue, which places a substantial burden on patients’ daily activities and lowers patients’ QOL, was lower in patients receiving darolutamide vs placebo,” the authors noted.

Disclosures: Martone stated she had nothing to disclose. The ARANOTE study was funded by Bayer and Orion Pharma.

References

1. Martone BK, Haresh KP, Shore N, et al. Efficacy and safety of darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer: phase 3 ARANOTE trial. Presented at: 50th Annual Oncology Nursing Society Congress; April 9-13, 2025; Denver, CO. Poster I8.
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):S1257-S1258. doi:10.1016/j.annonc.2024.08.2311
3. U.S. FDA accepts supplemental new drug application for Nubeqa (darolutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer. News release. Bayer. November 21, 2024. Accessed April 10, 2025. https://www.biospace.com/press-releases/u-s-fda-accepts-supplemental-new-drug-application-for-nubeqa-darolutamide-for-the-treatment-of-patients-with-metastatic-hormone-sensitive-prostate-cancer