1360MO Quality of life and patient-relevant endpoints with darolutamide in the phase III ARASENS study

Abstract

In ARASENS, darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% vs placebo (PBO) + ADT + docetaxel (HR 0.68, 95% CI 0.57–0.80) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). Given the potentially long treatment duration, the impact of DARO + ADT + docetaxel on pt-relevant endpoints is important to assess. Pts were randomized 1:1 to DARO 600 mg twice daily or PBO + ADT + docetaxel. Pt-relevant endpoints were all-cause and prostate cancer related death; time course of adverse events (AEs) of special interest; and quality of life (QoL) based on time to worsening (TTW) of disease-related physical symptoms. In the safety analysis set (n=1302), the DARO + ADT + docetaxel arm (n=652) had fewer all-cause deaths (35.1% vs 46.8%) and prostate cancer related deaths (26.1% vs 36.0%) vs the PBO + ADT + docetaxel arm (n=650). Despite longer treatment exposure with DARO vs PBO (median 41.0 vs 16.7 months), overall AE incidence was similar in the 2 arms. Fatigue (DARO 33.1%, PBO 32.9%) and rash (16.6%, 13.5%) appeared predominantly in treatment months 1–3 and incidence decreased rapidly thereafter. Cumulative incidences of falls, fractures, and mental impairment were low (<10%) and similar between arms. The incidence of cardiac disorders was constant over time and similar between arms (DARO 10.9%, PBO 11.7%). Incidence of hypertension was 13.7% vs 9.2%, with similar distribution over time. Most pts had high baseline QoL scores that were maintained over time, with comparable TTW in both arms.Table: 1360MOPopulationEvents, n/N* (%)HR95% CI†DAROPBOOverall351/651 (53.9)308/654 (47.1)1.040.89, 1.22ALP ≥ULN176/361 (48.8)154/363 (42.4)0.980.79, 1.22Bone metastases275/517 (53.2)248/520 (47.7)1.020.86, 1.21Visceral metastases59/111 (53.2)54/118 (45.8)1.040.72, 1.51Baseline pain score >0183/374 (48.9)153/360 (42.5)1.000.80, 1.24 Open table in a new tab Early treatment intensification with DARO + ADT + docetaxel improved pt-relevant endpoints, with reduced all-cause and prostate cancer related deaths and similar incidences and time course for most AEs of special interest vs PBO + ADT + docetaxel, notably with no increase in cardiac disorders. QoL was maintained over time, and DARO had no adverse impact on QoL, including in pts with poor prognosis.