DaroACT: Darolutamide and enzalutamide effects on physical and neurocognitive function and daily activity in patients with castration-resistant prostate cancer (CRPC).

Abstract

TPS5587 Background: The androgen receptor inhibitors (ARIs) apalutamide and enzalutamide (Enza) are approved for the treatment of men with advanced prostate cancer. These ARIs are associated with adverse events (AEs) including fatigue, neurocognitive dysfunction, and falls. Darolutamide (Daro) is a structurally distinct ARI approved by the FDA to treat nonmetastatic CRPC, based on significantly improved metastasis-free survival vs placebo in the ARAMIS Phase III clinical trial. Daro was not associated with a significant increase in AEs beyond that of concomitant androgen deprivation therapy, compared with placebo. DaroAcT is the first prospective trial to compare the effects of Daro to those of Enza on physical and neurocognitive function, and daily physical activity, in men with CRPC. Methods: This randomized, open-label, multicenter, Phase IIb trial (NCT04157088), involving ~20 sites across the US, is open for enrollment. After a lead-in phase of 30 pts treated with Daro alone, approximately 120 pts will be randomized 1:1 to receive Daro (600 mg twice daily) or Enza (160 mg once daily). Eligibility criteria include CRPC (metastatic and non-metastatic); age ≥18 years; Karnofsky performance status ≥80; no prior abiraterone within 6 months of enrollment, and no prior immunotherapy or apalutamide. All patients will continue luteinizing hormone-releasing hormone agonist or antagonist treatment for the duration of the study. The primary endpoint is the proportion of pts with slowed Timed Up and Go (TUG) time during the 24-week period from baseline. Secondary endpoints include the proportion of pts with worsening in short Physical Performance Battery (sPPB), mean change from baseline in daily physical activity, the proportion of pts with a decline in neurocognitive function or worsening of fatigue, and AEs. This study uses objective measures to assess physical function, including TUG and sPPB, measurements of daily activity levels with an accelerometry device for ≥7 days at designated time points, and neurocognitive tests. Fatigue is measured using the Brief Fatigue Inventory. Primary completion is estimated to be December 31, 2022. Clinical trial information: NCT04157088 .