Abiraterone, a drug that blocks endogenous androgen synthesis, is FDA approved for patients with metastatic high risk castration resistant prostate cancer (mCRPC) as well as metastatic high risk castration sensitive prostate cancer. However, large phase III trials have difficulty enrolling a significant number of black patients. In the pivotal COU-AA-302 phase III trial randomizing patients to abiraterone/prednisone vs placebo/prednisone for patients with mCRPC, 2.6% (28/1088) patients were black4.
In this prospective multicenter study, 50 black men and 50 white men with metastatic castration resistant prostate cancer received Abiraterone 1000 mg daily with prednisone 10 mg daily until disease progression or unacceptable adverse events. The primary objective was radiographic progression free survival. Key secondary endpoints was PSA kinetics and safety.
The baseline characteristics were similar between black and white patients. Median radiographic progression free survival was 16.8 months in both arms – this was consistent with the median rPFS seen in COU-AA-302 of 16.5 months5. PSA progression was different between white and black patients – median PSA PFS for black patients was 16.6 months and 11.5 months. A greater percentage of black patients had PSA declines of 30%, 50%, and 90%, and only 4 black patients had no PSA decline compared with 8 white patients. With respect to adverse events, both black and white patients had hypertension (42% vs 40%) but fatigue was more pronounced in white patients than black patients (40% vs 26%). Hypokalemia was greater in black patients (36% vs 18%). Exploratory analysis with single nucleotide polymorphism (SNP) profiling is underway to evaluate differences in genes regulating androgen metabolism and transport.
This was the first study to prospectively study the effect of abiraterone by race in a population of men with mCRPC. Results show that abiraterone is equally effective in black as white patients with respective to rPFS and black patients may have a more durable PSA response than white patients. This study also importantly shows that it is feasible to enroll a prostate cancer trial with 50% black men.
Presented By: Daniel J. George, MD. Duke Cancer Institute.
Written by: Jason Zhu, MD Fellow, Division of Hematology and Oncology Duke University Medical Center, Twitter: @TheRealdJasonZhu at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians 2017;67:7-30.
2.Nair RG, Geethakumari PR, Williams AAA, Lepore SJ. Abstract B17: Race and mortality in prostate cancer: A meta-analysis. Cancer Epidemiology Biomarkers & Prevention 2017;26:B17-B.
3.Wang B-D, Yang Q, Ceniccola K, et al. Androgen Receptor-Target Genes in African American Prostate Cancer Disparities. Prostate Cancer 2013;2013:15.
4.Efstathiou E, Deshpande H, George D, et al. Abstract CT313: An exploratory analysis of efficacy and safety of abiraterone acetate (AA) in black patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (ctx). Cancer Research 2014;74:CT313-CT.
5.Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology 2015;16:152-60.