ARASENS – Clinical trial

^{ARASENS Study Design  |  ARASENS Baseline Characteristics  |  ARASENS Trial Results  |  Tolerability}

In metastatic hormone-sensitive prostate cancer (mHSPC), NUBEQA (darolutamide) plus docetaxel plus ADT (otherwise known as NUBEQA (darolutamide) triplet therapy) was investigated in the ARASENS study, a Phase III, double-blind, placebo-controlled, multi-centre trial.

NUBEQA's efficacy is backed by robust clinical data and supported by international guidelines. NUBEQA is the only NICE-recommended and SMC-accepted therapy in combination with docetaxel and ADT.

^{* The secondary endpoints were tested with a hierarchical gatekeeping procedure. If the primary endpoint or a secondary endpoint did not reach significance, the hierarchical procedure was stopped, and subsequent analyses were considered to be exploratory.}

• This ARASENS study analysed 1,305 men with mHSPC (de novo + recurrent) who were randomised 1:1 to two arms: NUBEQA + ADT + docetaxel (n=651) and placebo + ADT + docetaxel (n=654).
• The primary endpoint of the study was overall survival (OS).

• NUBEQA + ADT + docetaxel: 33% reduced risk of death vs. placebo + ADT + docetaxel (primary endpoint)
• At 4 years, the overall survival rate with NUBEQA + ADT + docetaxel was 63% (95% CI: 58.7–66.7%) vs. 50% (95% CI: 46.3–54.6%) with placebo + ADT + docetaxel

• In mHSPC, patients receiving NUBEQA in combination with docetaxel + ADT stayed on treatment nearly 2.5 times longer compared to ADT + docetaxel
• After a standard course of concurrent docetaxel, most patients stayed on NUBEQA + ADT for a median of 3 further years, with patients receiving NUBEQA + ADT + docetaxel, having a median treatment duration of 41.0 months vs 16.7 months for patients receiving placebo + ADT + docetaxel
• When adding NUBEQA to ADT and docetaxel, almost 9 out of 10 patients completed all six docetaxel cycles (87.6% vs 85.5%, placebo + ADT+ docetaxel)
• The rate of AEs leading to permanent treatment discontinuation were similar between trial groups (13.7% with NUBEQA vs 10.6% with placebo + ADT and docetaxel)

The ARASENS Trial – AEs of special interest common to the ARI class

^*

• The most common adverse reactions in patients receiving NUBEQA in combination with docetaxel were rash (17.3%), alanine aminotransferase (ALT) increased (15.8%), aspartate aminotransferase (AST) increased (14.0%) and hypertension (13.8%)
• The most common serious adverse reactions in patients receiving NUBEQA in combination with docetaxel were febrile neutropenia (6.1%), neutrophil count decreased (2.8%) and pneumonia (2.5%)

^{* Adverse reactions incidences may not be attributed to NUBEQA alone but may contain contributions from other medicinal products used in combination.}

^{†† This category combines the following MedDRA terms: rash, rash maculopapular, drug eruption, rash pruritic, rash erythematous, rash macular, rash popular, rash follicular, rash vesicular, erythema, dermatitis. The incidence was highest during the first 6 months of treatment.}

^{‡‡ 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.}

^{§§ Includes hypertension, blood pressure increased, hypertensive emergency.}

Summary of the ARASENS trial

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

^{‡ ARASENS is a randomised, double-blind, placebo-controlled, Phase III trial involving patients with mHSPC. Patients (N=1305) were randomly assigned in a 1:1 ratio to receive NUBEQA + ADT + docetaxel (n=651) or placebo + ADT + docetaxel (n=664). The primary endpoint was OS, with time to mCRPC as a secondary endpoint (list of secondary endpoints is not exhaustive). 33% reduction in risk of death with NUBEQA + ADT + docetaxel vs ADT alone (HR: 0.68; 95% CI: 0.57-0.80: P<0.001). At 4 years, the overall survival rate with NUBEQA + ADT docetaxel was 63% (95% CI: 58.7-66.7%) vs 50% (95% CI: 46.3-54.6) with placebo + ADT + docetaxel. The time to development of castration-resistant disease was significantly longer in the darolutamide group (HR 0.36; 95% CI, 0.30-0.42; P<0.001).}

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