Recent data from the Phase III ARASENS trial showed that darolutamide plus androgen deprivation therapy (ADT) and docetaxel led to an overall survival benefit over placebo plus ADT and docetaxel in Black/African American patients with metastatic hormone-sensitive prostate cancer (mHSPC). This benefit was similar to what was observed in the overall population of the trial, according to findings presented during the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (Abstract B131).
"Blacks and African Americans are disproportionately affected by prostate cancer, having higher incidence rates and mortality rates compared with other racial and ethnic groups," noted study author Neal D. Shore, MD, Medical Director for the Carolina Urologic Research Center in Myrtle Beach, SC, during his presentation. "Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor. In patients with metastatic hormone-sensitive prostate cancer, darolutamide in combination with androgen deprivation therapy and docetaxel significantly reduced the risk of death by 32.5 percent compared with placebo plus ADT and docetaxel in the ARASENS study."
Based on previous findings from this trial, the FDA approved the combination of darolutamide/docetaxel/ADT for metastatic hormone-sensitive prostate cancer in August 2022. During the AACR conference, Shore presented the efficacy and safety of this combination therapy in the subgroup of Black/African American patients with metastatic hormone-sensitive prostate cancer.
Research Specifics
This randomized, placebo-controlled study was conducted in 286 centers and 23 countries worldwide. Eligible patients had metastatic hormone-sensitive prostate cancer with an ECOG performance status of 0 or 1. They also had to be candidates for ADT and docetaxel therapy in the opinion of the investigator, according to Shore.
All patients were randomly assigned to receive standard ADT plus docetaxel with or without darolutamide at 600 mg twice daily. The primary endpoint was overall survival. Secondary efficacy endpoints included the following: time to castration-resistant prostate cancer, time to pain progression, symptomatic skeletal event-free survival, time to first symptomatic skeletal event, time to initiation of subsequent antineoplastic therapy, time to worsening of disease-related physical symptoms, and time to initiation of opioid use for at least 7 consecutive days. Safety was assessed as treatment emergent adverse events, Shore explained.
A total of 54 Black and African American patients were randomized to the ARASENS study, 26 to the darolutamide arm and 28 to the placebo arm. The study authors reported that the demographics and baseline disease characteristics of this subgroup were generally similar to the those of the overall population. However, Shore noted that the Black/African American subgroup had a lower median age.
Additionally, a higher proportion of this patient group had an ECOG performance status of 1 and recurrent disease when compared with the overall population. While the median prostate-specific antigen levels were similar between the subgroup and the overall population, the data revealed that median alkaline phosphate levels were lower in Black and African American patients.
Key Findings
In these same patients, overall survival favored darolutamide in combination with ADT and docetaxel versus ADT and docetaxel alone, according to Shore. The 4-year overall survival rate for Black/African American patients who received the darolutamide combination was 61.7 percent compared with 40.9 percent for those who were given placebo.
"The darolutamide group also had longer time to castration-resistant prostate cancer compared with the placebo group, consistent with the overall population," Shore reported. "The safety profile of darolutamide in Black and African American patients was consistent with that observed for all patients.
"In this small subgroup, despite longer treatment duration with darolutamide, the number of patients with Grade 3 or 4 adverse events, serious adverse events, and discontinuations of study treatment due to adverse events in the darolutamide group were similar to those in the placebo group," he continued. "Adverse events associated with androgen receptor pathway inhibitors were similar between treatment groups and were generally consistent with the overall population."
Treatment emergent adverse events included fatigue, vasodilation or flushing, rash, diabetes or hyperglycemia, hypertension, cardiac disorders, bone fracture, fall, mental impairment disorders, decreased weight, depressed mood disorders, and breast disorders or gynecomastia.
"In this small population of Black and African American patients with metastatic hormone-sensitive prostate cancer from the ARASENS trial, darolutamide was associated with an improvement in overall survival and time to castration-resistant prostate cancer," Shore noted. "Darolutamide was well-tolerated and no new safety signals were observed.
"The efficacy and safety findings in Black and African American patients were consistent with the overall ARASENS population," he concluded. "We strongly encourage all clinical research investigators to optimize racial and ethnic accrual for both existing and future trials. Darolutamide is now approved by the FDA for treatment of patients with metastatic hormone-sensitive prostate cancer in combination with docetaxel and sets a new standard of care for the treatment of mHSPC."
Catlin Nalley is a contributing writer.