Efficacy and safety of darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel in Black/African-American patients from the phase 3 ARASENS trial

Abstract Introduction: Blacks/African-Americans (B/AAs) are disproportionately affected by prostate cancer, with higher incidence and mortality rates versus other racial/ethnic groups. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the ARASENS trial (NCT02799602), DARO in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI 0.57–0.80; P<0.001) vs placebo (PBO) + ADT with docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). We present efficacy and safety of DARO + ADT and docetaxel in B/AAs from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg or PBO twice daily in combination with ADT and docetaxel. The primary endpoint was overall survival (OS). Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety. Results: In ARASENS, 54 B/AAs received DARO (n=26) or PBO (n=28); 36/244 (14.8%) patients recruited in North America were B/AA. Baseline characteristics in the B/AA population were generally similar compared with the overall population, except for the proportion of pts who were <65 years of age (57.4% vs 36.6%), had ECOG performance status of 1 (37.0% vs 28.7%) and recurrent disease (24.1% vs 12.9%). Median prostate-specific antigen levels were similar (35.9 vs 27.6 μg/L), but alkaline phosphatase levels were lower in B/AAs (109.5 vs 143.0 U/L) vs all patients. In B/AAs, OS favored DARO + ADT + docetaxel vs PBO + ADT + docetaxel (stratified HR, 0.41; 95% CI, 0.17–1.02), with 4-year survival rates of 62% vs 41%. The DARO group also had longer time to CRPC vs PBO (median, not reached vs 12.6 months; HR, 0.09; 95% CI 0.02–0.30). The safety profile of DARO in B/AAs was consistent with that observed for all patients (grade 3/4 adverse events [AEs]: 57.7% vs 66.1%; serious AEs: 42.3% vs 44.8%). The occurrence of discontinuations of DARO/PBO due to AEs and AEs associated with androgen receptor pathway inhibitors (eg, fatigue/asthenia, vasodilation/flushing, hypertension, diabetes/hyperglycemia, cardiac disorders, fall, depressed mood disorders, rash, fracture, decreased weight, mental impairment, and breast disorders/gynecomastia) were similar between treatment groups in B/AAs and consistent with the overall population. Conclusions: In this small population of B/AAs with mHSPC from the ARASENS trial, DARO was associated with an improvement in OS and time to CRPC and was well tolerated. Efficacy and safety findings in B/AAs were consistent with the overall ARASENS population. Citation Format: Neal D. Shore, Maha H.A. Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Bertrand Tombal, Luke Nordquist, Michael Cookson, Jay Jhaveri, Silke Thiele, Shankar Srinivasan, Jorge Ortiz, Matthew R. Smith. Efficacy and safety of darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel in Black/African-American patients from the phase 3 ARASENS trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B131.