Darolutamide Plus ADT and Docetaxel Improves Quality of Life Vs Placebo in mHSPC

Quality of life data from the phase 3 ARASENS study highlighted how early treatment intensification with darolutamide plus standard androgen deprivation therapy and docetaxel improved patient-relevant end points compared with placebo in the management of metastatic hormone-sensitive prostate cancer.

Patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received early treatment intensification with darolutamide (Nubeqa) plus standard androgen deprivation therapy (ADT) and docetaxel (Taxotere) experienced an improvement in patient-relevant end points compared with placebo in combination with ADT and docetaxel, according to a quality of life analysis from the phase 3 ARASENS study (NCT02799602).

At baseline, most patients had high quality of life scores in terms of the Brief Pain Inventory–Short Form (BPI-SF) scale, with 40.8% of patients reporting no pain and 39.8% reported mild pain in the overall population of 1305 patients. Moreover, in the total treatment population, 9.5% of patients experienced moderate pain and 6.9% had severe pain.

Investigators reported that the times to worsening of disease-related physical symptoms and pain interference were maintained following darolutamide treatment in the overall treatment population. The median time to worsening of National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy Prostate Cancer Symptom Index 17-item questionnaire (NCCN-FACT-FPSI17) physical symptoms was 19.3 months (95% CI, 13.8-24.8) for the darolutamide arm and 19.4 months (95% CI, 15.4-27.6) for the placebo arm (HR, 1.04; 95% CI, 0.89-1.22). In a planned exploratory analysis, the median time to worsening of BPI-SF pain interference was not estimable (NE) in the darolutamide arm and the placebo arm (HR, 0.86; 95% CI, 0.64-1.15).

The randomized, double-blind, placebo-controlled phase 3 ARASENS study enrolled a total of 1306 patients across 286 treatment centers in 23 countries. Patients were randomly assigned 1:1 to either receive 600 mg of darolutamide or matched placebo twice a day plus ADT and 6 cycles of docetaxel.

The primary end point of the study was overall survival (OS). Secondary end points included time to castration-resistant prostate cancer, time to pain progression, symptomatic skeletal events (SSEs), time to first SSE, time to initiation of subsequent systemic antineoplastic therapies, time to worsening of disease-related physical symptoms, and safety.

Patients were eligible to enroll on the study with histologically or cytologically confirmed prostate adenocarcinoma and metastatic disease. Additional requirements for patients included being candidates for ADT and docetaxel, having an ECOG performance status of 0 or 1, and having adequate bone, liver, and marrow function. The study also stratified patients based on extend of disease and alkaline phosphatase level.

Among patients with moderate or severe baseline pain, a post hoc exploratory analysis highlighted a trend towards a delay in time to worsening of disease-related physical symptoms and pain interference in the darolutamide cohort vs the placebo cohort. The median time to worsening of physical symptoms for patients with moderate or severe baseline pain was 41.4 months (95% CI, 36.1-NE) for the placebo arm and not estimable for the darolutamide arm (95% CI, NE-NE; HR, 0.63; 95% CI, 0.39-1.04). The median time to worsening of BPI-SF pain interference among patients with moderate or severe baseline pain was not estimable for either treatment arm (HR, 0.60; 95% CI, 0.29-1.24).

The cumulative incidence of adverse effects was comparable and generally low across both arms. For patients in the darolutamide and placebo arms, respectively, the estimated cumulative incidence of time to fall was 6.6% vs 4.6% (HR, 1.05; 95% CI, 0.65-1.69), time to fatigue incidence was 33.1% and 32.9% (HR, 0.95; 95% CI, 0.79-1.15), and the time to fracture incidence was 7.5% and 5.1% (HR, 1.09; 95% CI, 0.70-1.70). Moreover, the estimated cumulative incidence of time to mental impairment disorder was 3.5% and 2.3% (HR, 1.16; 95% CI, 0.60-2.25), the incidence of time to rash was 16.6% and 13.5% (HR, 1.15; 95% CI, 0.87-1.53), the incidence of time to cardiac disorder was 10.9% and 11.7% (HR, 0.76; 95% CI, 0.54-1.05), and the incidence of time to hypertension was 13.7% and 9.2% (HR, 1.20; 95% CI, 0.86-1.67) across both respective arms.

Based on a safety analysis set, investigators indicated that darolutamide lowered the risk of death by 32.5% compared with placebo. Moreover, fewer prostate cancer-related deaths were observed in the darolutamide arm vs the placebo arm, further confirming the regimen’s survival benefit. The 48-month survival probability in terms of prostate-cancer-related deaths was 70.8% for the darolutamide arm vs 58.3% for the placebo arm (HR, 0.65; 95% CI, 0.53-0.79). In terms of overall survival (OS), the 48-month rate was 62.7% for the darolutamide arm and 50.4% for the placebo arm (HR, 0.68; 95% CI, 0.57-0.80; P <.0001).

The results of the study read out at the 2022 European Society for Medical Oncology (ESMO) Congress.

Reference

Fizazi K, Smith MR, Hussain M, et al. Quality of life and patient-relevant endpoints with darolutamide in the phase III ARASENS study. Ann Oncol. 2022;33(suppl 7):S616-S652. doi:10.1016/annonc/annonc1070