News Release

Darolutamide Showed similar benefits for Black/African American patients as observed in the overall population of the ARAMIS trial

Reports and Proceedings

American Association for Cancer Research

PHILADELPHIA – Black/African American patients with prostate cancer who were treated with the androgen receptor inhibitor darolutamide (Nubeqa) had clinical outcomes similar to those observed in the overall clinical trial population, according to results from the ARAMIS phase III clinical trial presented at the 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held online October 6-8, 2021.

“Compared with other racial and ethnic groups, Black/African American individuals have disproportionately higher rates of prostate cancer incidence and mortality,” said presenter Neal Shore, MD, the medical director of the Carolina Urologic Research Center. “Despite this disparity, many clinical trials of prostate cancer therapies fail to publish demographic information on race and ethnicity.”

The ARAMIS phase III clinical trial was designed to evaluate the efficacy and safety of the androgen receptor inhibitor darolutamide compared with placebo in combination with androgen-deprivation therapy in patients with high-risk nonmetastatic castration-resistant prostate cancer. In contrast to existing androgen receptor inhibitors, darolutamide exhibits low penetration of the blood-brain barrier and, therefore, may be associated with less risk of adverse events of the central nervous system, explained Shore. In addition, he noted that darolutamide has low potential to interact with other common medications.

Shore and colleagues previously reported that darolutamide significantly improved metastasis-free survival and overall survival and exhibited a favorable safety profile in patients enrolled in the ARAMIS trial. Their latest analyses evaluated the safety and efficacy of darolutamide specifically for the Black/African American patients enrolled in the trial.

Among the 52 Black/African American patients included in the analysis, 28 were treated with darolutamide, and 24 received placebo. Patients treated with darolutamide compared with those who received placebo had longer metastasis-free survival (median not reached in the darolutamide arm vs. 12.4 months) and a higher three-year overall survival rate (100 percent vs. 71 percent). Men treated with darolutamide also had longer time to first cytotoxic chemotherapy and longer time to disease progression.

Furthermore, the safety profile of darolutamide among Black/African American patients was consistent with the results from the overall study population. The incidence of adverse events (82 percent vs. 92 percent) and treatment discontinuation due to adverse events (4 percent vs. 17 percent) was lower for darolutamide-treated patients compared with placebo-treated patients.

“Darolutamide showed similar benefits for Black/African American patients as observed in the overall ARAMIS population,” said Shore. “Our study provides important findings that help to address the lack of data in Black/African American patients who are disproportionally affected by prostate cancer. Additional research is warranted to better understand the disparity in outcomes in these patients and help guide treatment choices tailored to their individualized health care needs.”

A limitation of the study was the small sample size of Black/African American patients enrolled in the ARAMIS trial. “In future clinical trials, we need to improve participation of underrepresented populations through such efforts as building trust in the health care system, utilizing patient advocates, and increasing awareness and educational opportunities,” Shore noted.

The study was supported by Bayer AG and Orion Pharma.

Shore is an employee of GenesisCare and has served on the speaker’s bureau and as a consultant/advisor for Bayer, Janssen Scientific Affairs, Dendreon, Tolmar Inc., Ferring Pharmaceuticals, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, Myovant Sciences, Astellas Pharma, AbbVie, Merck, Bristol Myers Squibb/Sanofi, Boston Scientific, Clovis Oncology, Exact Imaging, FerGene, Foundation Medicine, CG Oncology, InVitae, MDxHealth, Myriad Genetics, Nymox, Propella Therapeutics, Genzyme, Sanofi, and Sesen Bio. Shore has received research support from AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Boston Scientific, Clovis Oncology, Dendreon, Exact Imaging, Ferring, Foundation Medicine, InVitae, Janssen, MDxHealth, Merck, Myovant Sciences, Myriad Genetics, Nymox, Pfizer, Sanofi, Sesen Bio, and Tolmar Inc.


Title: Efficacy and safety of darolutamide in Black/African American patients from the phase III ARAMIS trial

Introduction and Objective: Higher incidence and mortality rates of prostate cancer (PC) have been observed in black and African-American men (B/AAs) compared with other racial and ethnic groups. B/AAs with PC are more likely to be diagnosed at a younger age with more extensive disease and exhibit differential gene expression associated with more aggressive disease, but they are less likely to receive therapy compared with white men. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the phase III ARAMIS trial, DARO significantly improved metastasis-free survival (MFS) and overall survival (OS) with a favorable safety profile in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). We present the efficacy and safety of DARO in B/AAs from ARAMIS.

Methods: Men with nmCRPC were randomized 2:1 to DARO (n=955) or placebo (PBO; n=554). The primary endpoint was MFS. Secondary endpoints included OS and time to first cytotoxic chemotherapy, prostate-specific antigen (PSA) progression, pain progression, and first symptomatic skeletal event (SSE). Adverse events (AEs) were assessed.

Results: 52 B/AAs received DARO (n=28) or PBO (n=24) in ARAMIS. At baseline, the B/AA group treated with DARO had a median time from diagnosis of 101 months and 50% (n=14) had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1; the median time from diagnosis in the entire DARO-treated population in ARAMIS was 86 months and 32% had ECOG PS of 1. At primary analysis data cutoff (3 Sept 2018), DARO improved MFS vs PBO (median: not reached vs 12.4 months) in the B/AAs group. At final analysis data cutoff (15 Nov 2019), 3-year OS rates were 100% (DARO) vs 71% (PBO). DARO showed longer time to first cytotoxic chemotherapy and PSA progression vs PBO. Time to pain progression and time to SSE were not evaluable due to the very low number of events. The safety profile of DARO in B/AAs was consistent with that observed for all patients. Fewer AEs (82% vs 92%) and discontinuations due to AEs (4% vs 17%) were reported with DARO vs PBO in the B/AA group.

Conclusions: In this small population of B/AAs with nmCRPC, DARO was associated with an improvement in MFS, OS, and other secondary efficacy outcomes and was well tolerated. Efficacy and safety findings are consistent with the overall ARAMIS population.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.