A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate‐resistant prostate cancer

Abstract

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone

“…Favorable outcomes for African American men receiving abiraterone were previously observed in retrospective studies, 4,5 but no significant race-based differences in abiraterone effectiveness were found in prospective data. 6,7 It is unclear, however, whether the lack of significant differences in these prospective studies was due to insufficient power. Our study suggests that abiraterone is associated with better outcomes for African American vs non-Hispanic White men in real-world practice and extends prior analyses by investigating race-specific overall survival in a large real-world cohort.…”

“…[4][5][6][7] African American patients treated with abiraterone in the Abi-Race prospective trial had longer median time to prostate-specific antigen progression than non-Hispanic White patients (16.6 vs 11.5 months, respectively) and higher rates of at least 50% prostate-specific antigen decline (74% vs 66%, respectively); however, these differences were not statistically significant. 7 It is unclear whether these outcomes extend to contemporary real-world cohorts, particularly given availability of other effective therapies, such as enzalutamide. We investigated differences in outcomes associated with first-line abiraterone between African American and non-Hispanic White men with mCRPC in a national real-world cohort, which to our knowledge represents a larger sample size with greater power than that of similar investigations to date.…”

Racial disparities in prostate cancer: A complex interplay between socioeconomic inequities and genomics

“…In the first ever prospective multicenter study stratified by race ( NCT01940276 ), George and colleagues found that, relative to White men with mCRPC, Black men are more likely to have greater and more durable PSA responses to a combination of abiraterone acetate (Zytiga) and prednisone [ 51 ]. Abiraterone acetate is a selective, irreversible inhibitor of CYP17 and can suppress adrenal synthesis of androgen precursors as well as in situ steroidogenesis in the tumor microenvironment.…”

Genetic Contributions to Prostate Cancer Disparities in Men of West African Descent

“…This increased overall survival reported in AA men occurred despite younger age, worse performance status, higher testosterone, higher PSA, and lower hemoglobin described within this population. In a prospective, multicenter study of 100 mCRPC patients treated with abiraterone acetate and prednisone entitled ABI RACE, AA patients experiences greater median PSA progression-free survival rates as well as increased rates of PSA decline ( 152 ). While adverse events were similar in all patients, fatigue was notably lower in AA men.…”