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ARANOTE – Clinical trial

^{ARANOTE Clinical trial}^|^{ARANOTE Baseline Characteristics}^|^{ARANOTE trial results: primary endpoint}^|^{ARANOTE trial results: secondary endpoints}^|^Tolerability

In metastatic hormone-sensitive prostate cancer (mHSPC), NUBEQA (darolutamide) plus ADT was investigated in ARANOTE, a Phase III, double-blind, placebo-controlled, multi-centre trial.

Following the approval of the ARASENS (NUBEQA + docetaxel +ADT) and ARANOTE (NUBEQA + ADT) trial indications in mHSPC, NUBEQA is the only second generation ARI with the versatility to be used both with and without docetaxel, offering flexibility to your treatment decisions.

ARANOTE Clinical trial - Study Design

ARANOTE was a global, randomised, double-blind, placebo-controlled, parallel-group, Phase III study.
This study analysed 669 men with mHSPC who were randomised 2:1 to two arms: NUBEQA + ADT (n=446) and placebo + ADT (n=223). All participants started ADT within 12 weeks before initiating study treatment.
The ARANOTE Trial was designed and powered to evaluate the efficacy (with a primary endpoint of radiological progression-free survival) of NUBEQA + ADT vs ADT + placebo.

Secondary Endpoints^*

Overall survival
Time to initiation of subsequent systemic anti-cancer therapy
Time to mCRPC
Time to PSA progression
PSA undetectable rate (PSA 0.2ng/ml)
Time to pain progression (BPI-SF)
Safety

^{* Secondary efficacy end points were tested for statistical significance using a hierarchical gatekeeping procedure only if the primary end point was statistically significant (two- sided alpha of .05) using the same alpha in the following order: OS, time to initiation of subsequent systemic anti-cancer therapy, time to mCRPC, time to PSA progression, rates of PSA <0.2 ng/mL, and time to pain progression.}

Expert insights on the trial design - hear from Professor Fred Saad, the ARANOTE Clinical Trial primary investigator.

Prescribing information for NUBEQA® (darolutamide) can be found here.

ARANOTE enrolled men with mHSPC similar to those typically seen in clinical practice

^{Demographic and baseline characteristics were well-balanced across both treatment arms.}

^{** Centrally assessed.† Recurrent disease is defined as stage I to IVA, and de novo is defined as stage IVB at initial diagnosis. ‡ Disease volume defined by CHAARTED criteria: presence of visceral metastases and/or at least four bone metastases with at least one beyond vertebral bodies and pelvis. § Tumour-node-metastasis system. M1a: nonregional lymph-node metastases only; M1b: bone metastases with or without lymph-node metastases; M1c: visceral metastases with or without lymph-node or bone metastases.}

ARANOTE trial results: Primary endpoint

Radiographic progression free survival (rPFS)

NUBEQA is clinically proven to significantly reduce the risk of radiographic progression or death by 46P%^† when adding NUBEQA to ADT. Absolute risk at 2 years, 18.2%, HR: 0.54; 95% CI: 0.41‒0.71; p<0.0001.

^{† NUBEQA + ADT vs Placebo + ADT.}

ARANOTE trial results - primary endpoint

Patient with High and Low volume disease
Radiological progression-free survival rates at 24 months were 70.3% with NUBEQA + ADT vs 52.1% with placebo + ADT.
The benefit of NUBEQA on rPFS was consistent across all prespecified subgroups, including patients with high and low volume disease.
In the ARANOTE Clinical Trial, high-volume disease was defined by CHAARTED criteria: presence of visceral metastases and/or 4 bone metastases with 1 beyond the vertebral column and pelvis. Low-volume disease was defined as not meeting these criteria.

ARANOTE trial results: Secondary endpoints

Overall survival at time of primary analysis

At the primary analysis, NUBEQA + ADT was associated with a 19% reduction in the risk of death (Absolute risk at 2 years: 4.2%; HR, 0.81 [95% CI, 0.59 to 1.12])

^{* NUBEQA + ADT vs placebo + ADT}

Deepen your understanding of the ARANOTE trial design:

The ARANOTE study's primary endpoint is rPFS, clinically accepted for efficient evaluation of treatment effectiveness
A study powered to test for OS requires larger trial sizes and longer follow-up, making it challenging to enrol and retain patients amid increasing access to treatment options for mHSPC

^{The HR and 95% CI were calculated using the Cox regression model stratified by the presence of visceral metastases and prior therapy.}

NUBEQA + ADT offers clinical benefit in a number of secondary endpoints versus placebo + ADT

Hazard ratio and 95% CI are based on Cox regression model, stratified by visceral disease (present v absent) and prior local therapy (yes vs no).
OS did not reach statistical significance and, as per the hierarchical testing of the SAP, none of the other secondary endpoints were tested for statistical significance All p values are nominal.

ADT offers significant benefit in a number of secondary endpoints versus placebo + ADT

ARANOTE Tolerability

NUBEQA‘s proven tolerability helps patients to continue treatment, with lower discontinuation rates due to AEs with NUBEQA + ADT versus placebo + ADT (6.1% vs 9.0%).

Median duration of treatment at time of data cutoff

Discontinuation rate in ARANOTE

In the ARANOTE trial, patients receiving NUBEQA + ADT stayed on treatment nearly 7 months longer compared to ADT + placebo (median treatment duration, 24.2 months, NUBEQA + ADT vs 17.3 months, placebo + ADT)
In the pooled analysis of ARANOTE and ARAMIS, 96% of patients were treated with NUBEQA + ADT without a dose reduction
The discontinuation rate for NUBEQA + ADT due to AEs was 6.1% vs 9.0% for placebo + ADT
In mHSPC, NUBEQA is the only second generation ARI with fewer discontinuations versus placebo when added to ADT in Phase III clinical trial

^{* NUBEQA + ADT vs placebo + ADT}

ARANOTE Trial Results: Tolerability

NUBEQA‘s proven tolerability helps patients to continue treatment, with lower discontinuation rates due to AEs with NUBEQA + ADT versus placebo + ADT (6.1% vs 9.0%).

In the ARANOTE trial, patients receiving NUBEQA + ADT stayed on treatment nearly 7 months longer compared to ADT + placebo (median treatment duration, 24.2 months, NUBEQA + ADT vs 17.3 months, placebo + ADT)
In the pooled analysis of ARANOTE and ARAMIS, 96% of patients were treated with NUBEQA + ADT without a dose reduction
The discontinuation rate for NUBEQA + ADT due to AEs was 6.1% vs 9.0% for placebo + ADT
In mHSPC, NUBEQA is the only second generation ARI with fewer discontinuations versus placebo when added to ADT in Phase III clinical trial

^{* NUBEQA + ADT vs placebo + ADT}

^{Image Footnotes:}^{* This category combines the following MedDRA terms: rash, rash macular, rash maculo-papular, rash papular, rash pustular, erythema, dermatitis. † Excluding pathologic fractures. This category combines the following MedDRA terms: any fractures and dislocations, limb fractures and dislocations, pelvic fractures and dislocations, spinal fractures and dislocations, and thoracic cage fractures and dislocations. ‡ This category is a MedDRA High-Level Group Term. § Includes fatigue and asthenia, lethargy and malaise. ¶ Includes arteriosclerosis coronary artery, coronary artery disease, coronary artery occlusion, coronary artery stenosis, acute coronary syndrome, acute myocardial infarction, angina pectoris, angina unstable, myocardial infarction, myocardial ischaemia.}

Summary of the ARANOTE trial

Choose NUBEQA for efficacy that doesn’t compromise your patients’ QoL.

The only second generation ARI approved for mHSPC with and without docetaxel.

mHSPC | ARANOTE § (without chemo)

Clinically proven: Significantly reduce the risk of radiographic progression or death by 46%^** when adding NUBEQA to ADT

^{**Absolute risk at 2 years: 18.2%; HR: 0.54; 95% CI: 0.41‒0.71; p<0.0001.}

^{§ ARANOTE is a randomised, double-blind, placebo-controlled, Phase III trial involving patients with mHSPC. Patients (N=669) were randomly assigned in a 2:1 ratio to receive NUBEQA + ADT (n=446) or placebo + ADT + docetaxel (n=223). The primary endpoint was rPFS, with OS and time to mCRPC as a secondary endpoint (list of secondary endpoints is not exhaustive). NUBEQA +ADT significantly reduced the risk of progression or death by 46% versus placebo +ADT (HR, 0.54; 95% CI, 0.41-0.7; P< .0001), with median rPFS not reached in the NUBEQA + ADT group versus 25.0 months in the placebo+ ADT group. The rPFS rates at 24 months were 70.3% in the NUBEQA + ADT group and 52.1% in the placebo + ADT group.}

Refer to full Summary of Product Characteristics (SmPC) before prescribing.

For my patients who require treatment intensification, can I use NUBEQA as a triplet in combination with docetaxel and ADT in mHSPC? What are the key outcomes from the ARASENS trial?

Clinically proven and recommended by NICE: Significantly extend survival and reduce the risk of death by >30%^† when adding NUBEQA to ADT and docetaxel

^{† Absolute risk at 4 years: 12.3%; HR: 0.68; 95% CI: 0.57‒0.80; p<0.0001.}

Learn about key outcomes from the ARASENS trial

Learn about NUBEQA’s Safety Profile and Side Effects

Abbreviations

^{ADT, androgen deprivation therapy; AE, adverse event; ARI, androgen receptor inhibitor; BPI-SF, Brief Pain Inventory-Short Form; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; mCRPC, metastatic castration-resistant prostate cancer; MedDRA, Medical Dictionary for Regulatory Activities; mHSPC, metastatic hormone-sensitive prostate cancer; NR, not reached; OS, overall survival; p, p-value; PSA, prostate-specific antigen; QoL, quality of life; rPFS, radiological progression-free survival.}

PP-NUB-GB-2542 | August 2025

ARASENS Clinical Trial

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