Black men achieve deeper response to abiraterone acetate for advanced prostate cancer

CHICAGO — Black men with metastatic castration-resistant prostate cancer achieved deeper and more durable responses to abiraterone acetate than white men, according to results of the prospective, multicenter Abi Race study presented at ASCO Annual Meeting.

The findings align with observations from retrospective studies that suggested superior response to abiraterone acetate (Zytiga, Janssen) among black men.

“There really are three take-home messages,” Daniel George, MD, professor of medicine and surgery at Duke University, said during a press conference. “First, prospective multicenter race-based studies in prostate cancer are feasible. We can do this. Second, we absolutely need to do this. There are differences in both outcomes of treatment, as well as side effects, that could have significant implications for how we use and when we use these drugs. Third, there are genetic differences underlying race, and we need to understand what those are and how they correspond with these outcomes.”

Black men are 1.6 times more likely than white men to develop prostate cancer; however, they are 2.4 times as likely to die of the disease.

Black men were underrepresented in clinical trials that led to the approval of abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer. Consequently, evidence is limited about the potential differences between racial groups with regard to treatment efficacy and adverse events.

Retrospective analyses suggested black men achieved greater PSA responsiveness to abiraterone than white men.

“However, these numbers were to small to statistically draw any conclusions,” George said.

George and colleagues conducted the noncomparative, open-label Abi Race study to prospectively assess whether outcomes differed between black men and white men treated with abiraterone and prednisone for advanced disease.

The study included 100 men with metastatic castration-resistant prostate cancer. Participants self-identified themselves as white (n = 50) or black (n = 50).

Baseline characteristics were similar between the two groups.

A higher percentage of white patients underwent prior treatment with sipuleucel-T (Provenge, Dendreon [40% vs. 24%]) and docetaxel (22% vs. 16%).

A higher percentage of black men had hypertension (58% vs. 23%), hypercholesterolemia (60% vs. 40%) and hyperglycemia (14% vs. 10%) at baseline.

“Many of those factors would have excluded them from large prospective phase 3 studies,” George said. “We chose liberal criteria to allow patients on this study in order to maximize the eligibility for our populations.”

Participants received standard treatment with 1,000 mg daily abiraterone and 10 mg twice-daily prednisone. Treatment continued until disease progression or unacceptable adverse events.

Radiographic PFS served as the primary objective. Key secondary endpoints included safety and PSA kinetics.

Researchers reported similar median radiographic PFS among black men (16.7 months; 95% CI, 12.6-22.1) and white men (16.5 months; 95% CI, 11-not reached).

“Importantly, African-Americans didn’t show any trend toward worse outcomes, as we might have expected [due to their] higher rate of death from prostate cancer,” George said. “A larger study would be necessary to show any statistical difference between these populations.”

However, median time to PSA worsening was longer among black men (16.6 months; 95% CI, 11.5-not reached) than white men (11.5 months; 95% CI, 8.5-19.3).

Higher percentages of black men than white men achieved PSA declines greater than 30% (82% vs. 78%), greater than 50% (74% vs. 66%) and greater than 90% (48% vs. 38%).

The rate of tumor flare — defined as appearance of new lesions while PSA is declining — was four times higher among black men (16% vs. 4%).

“This suggests there might be a different biologic response to this therapy among African-American patients versus Caucasian patients,” Georg said.

Researchers reported longer median time to PSA progression among black men (16.6 months vs. 11.5 months).

A higher percentage of black men developed hyperglycemia (26% vs. 14%), hypokalemia (36% vs. 18%) and hot flashes (20% vs. 2%). The higher occurrence of these hormonal-based toxicities suggests a greater exposure risk to abiraterone among these patients.

Exploratory analyses showed single-nucleotide polymorphism patterns varied by race, as well as by extent of African ancestry. George and colleagues intend to look at specific genes that might be responsible for these differences.

Additional prospective studies of black patients are necessary to better elucidate the effect of racial determinants on outcomes after treatment with new hormonal regimens, George said.

A 100-patient study is underway to evaluate outcomes of treatment with abiraterone plus apalutamide (Erleada, Janssen). George and colleagues also are coleading an effort to study all treatments of men with advanced prostate cancer through IRONMAN, a global 5,000-patient registry. – by Mark Leiser

For more information:

George DJ, et al. Abstract LBA5009. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: The researchers report funding from Janssen. George reports consultant or advisory roles with Acceleron Pharma, Astellas, Bayer, Bristol-Myers Squibb, Celgene, Dendreon, Exelixis, Genentech, GlaxoSmithKline, Innocrin, Janssen, Medivation, Merck Sharpe & Dohme, Myovant Sciences, Novartis, Pfizer and Sanofi; speakers bureau roles with Bayer, Exelixis and Sanofi; travel, accommodations and expenses from Bayer, Exelixis, Genentech/Roche, Medivation, Merck and Pfizer; and honoraria from Axess Oncology, Bayer, BioPharm International, Dendreon, Medivation, Novartis and Sanofi; and research funding to his institution from Acerta Pharma, Astellas, Bayer, Bristol-Myers Squibb, Dendreon, Exelixis, Genentech/Roche, Innocrin, Janssen, Millennium/Takeda, Novartis and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.