Abstract Introduction and Objective Prostate cancer is a leading cause of death among Black/African American patients worldwide. Although phase 3 studies are the gold standard, their strict study inclusion criteria may restrict generalizability. Real-world evidence can enhance our understanding of treatment effectiveness in clinical settings. This analysis evaluates darolutamide treatment in Black/African American nmCRPC populations from three different studies. Methods ARAMIS (global, randomized, placebo-controlled, phase 3 trial) included nmCRPC patients with prostate-specific antigen (PSA) ≥2 ng/mL and PSA doubling time (PSADT) ≤10 months. DAROL (global, prospective, observational study) and DEAR-EXT (US, retrospective, chart-review cohort study) included nmCRPC patients for whom the decision to initiate darolutamide treatment was made pre-enrollment at the discretion of the treating physician, who had disease progression despite treatment with ADT, no evidence of metastases on conventional imaging (DAROL), and no evidence of metastases in physician notes or metastasis codes before initiating androgen receptor inhibitor treatment (DEAR-EXT). Key outcomes included PSA response, metastasis-free survival (MFS), overall survival (OS), and safety (treatment-emergent adverse events TEAEs, which may not be as well-captured in real-world retrospective chart reviews). Results Baseline characteristics in Black/African American patients (ARAMIS n=28; DAROL n=23; DEAR-EXT n=116) varied slightly between studies: median age was ARAMIS 73 y, DAROL 74 y, DEAR-EXT 79 y; 64%, 67%, and 60%, respectively, had Gleason score 8. Median baseline PSA in ARAMIS, DAROL and DEAR-EXT was 8.3, 4.2, and 4.1 ng/mL; median PSADT was 4.9, 5.8, and 8.7 months. At any time, the proportion of patients reaching 90% reduction in PSA from baseline was ARAMIS 79%, DAROL 86%, DEAR-EXT 74%; 2-y MFS rates were 100%, 89%, and 76%; and 2-y OS rates were 100%, 89%, and 95%. Incidences of any-grade TEAEs were 82% and 70% in the prospective ARAMIS and DAROL studies, and 22% in the retrospective DEAR-EXT study; only fatigue showed ≥10% incidence (14–22%) in all three studies. TEAEs led to discontinuation in 4–10% of patients in each study, indicating consistent tolerability. Conclusion Black/African American patient populations are often underrepresented in clinical trials. This analysis of data from clinical and real-world prospective and retrospective studies indicated that despite differences in study designs and settings, darolutamide was effective and well-tolerated. Clear benefits in PSA response, MFS and OS were observed with darolutamide treatment in Black/African American patients across the ARAMIS, DAROL and DEAR-EXT studies. Citation Format: Christopher Pieczonka, Geoffrey Gotto, Nasreen Khan, Patrick Adorjan, Mercedeh Ghadessi, Frank Verholen, Neal Shore. Efficacy and safety of darolutamide in Black/African American patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) across clinical and real-world studies: An analysis of ARAMIS, DAROL, DEAR-EXT abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C119.
Pieczonka et al. (Thu,) studied this question.
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