ASCO GU 2021: Racial Disparities in Efficacy of First-Line Abiraterone in Metastatic Castrate-Resistant Prostate Cancer

(UroToday.com) It is increasingly well-known that African American (AA) men as a group experience higher incidence of prostate cancer and worse prostate cancer-specific outcomes. The reasons for this are the point of ongoing investigations, with contributors to disparity from biological and non-biological factors. Within the realm of differential biology lie the data that AA men have demonstrated more pronounced prostate-specific antigen (PSA) responses as compared to white counterparts when treated with abiraterone acetate in the metastatic castration-resistant setting (mCRPC),1 and with subsequent prospective studies indicating improved progress-free survival in this same population (as compared to non-Hispanic white patients).2 Dr. Mallika Marar and colleagues sought to determine, retrospectively, whether similar demographic-based differences in the efficacy of abiraterone acetate exist in real-world practice.

In a retrospective study using de-identified data from Flatiron Heath, the authors evaluated patients who received systemic therapy for mCRPC over a seven-year period (2012-2018). Statistical adjustments were made to adjust for confounding, using a variety of covariates including demographics (age, race, comorbidity index), clinical factors (PSA level, baseline use of steroids or opioids), and care delivery (insurance status, practice type, and region). The primary outcome was overall survival (OS) with time-to-next-treatment (TTNT) as the secondary outcome.

The authors present an impressively large cohort of 3,808 patients, of whom 404 identified as AA (10.6%) and 2,165 identified as non-Hispanic white (NHW) (68.7%). Abiraterone was the most common first-line therapy (1,729, 45.4%) followed by enzalutamide (1,255, 33%), and docetaxel (549, 14.4%). Use of abiraterone acetate was more frequent in older patients and in patients treated at academic centers (8% vs. 6%). Median overall survival was improved in AA versus NHW men receiving first-line abiraterone acetate (24 vs. 17 months, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.02-1.71, see figure).  Remarkably, receipt of abiraterone acetate was not associated with a change in OS among AA men, as compared to those AA men who did not receive the potent androgen receptor (AR) signaling inhibitor. In contrast, not receiving first-line abiraterone acetate was associated with worse OS in NHW (17 vs. 20 months, HR 1.16, 95% CI 1.04-1.30, see table). Interaction of race-by-treatment was significant for OS in those subjects receiving first-line abiraterone acetate (coefficient of interaction 0.27). TTNT did not differ by self-reported race.

Median overall survival was improved in AA versus NHW men receiving first line abiraterone acetate


These data, as presented by Dr. Marar et al. add to further evidence that the prostate tumors of AA men may respond to abiraterone acetate better than those tumors of NHW. Here, they also carefully isolate the variable of self-reported race and demonstrate a comparative OS survival advantage. What stands out is that there was no observed advantage among AA men to receiving abiraterone acetate in the first-line, suggesting that outcomes in this population, as previously reported as worse versus NHW, may be worse due to non-biological factors, such as care access and delivery metrics. Additional clarity may come from using genomic tools to isolate both global (predominant) and local (locus-specific) ancestry. These data support the first-line use of abiraterone acetate in AA men with mCRPC, and also highly the need for carefully designed prospective studies, including molecular assessments of tumor and tumor microenvironment, to determine the source of the reported effects of abiraterone acetate in AA men with prostate cancer.

the source of the reported effects of abiraterone acetate in AA prostate cancer

Presented by: Mallika Marar, MBA, MD, Resident Physician, Radiation Oncology, Stanford University, San Francisco, California

Written by: Jones Nauseef, MD, PhD, Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, Twitter: @DrJonesNauseef during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

References:

1. Ramalingam, Sundhar, Michael S. Humeniuk, Rachel Hu, Julia Rasmussen, Patrick Healy, Yuan Wu, Michael R. Harrison, Andrew J. Armstrong, Daniel J. George, and Tian Zhang. "Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate–resistant prostate cancer." In Urologic Oncology: Seminars and Original Investigations, vol. 35, no. 6, pp. 418-424. Elsevier, 2017.

2. George, Daniel J., Elisabeth I. Heath, A. Oliver Sartor, Guru Sonpavde, William R. Berry, Patrick Healy, Carolyn Winters et al. "Abi Race: a prospective, multicenter study of black (B) and white (W) patients (pts) with metastatic castrate resistant prostate cancer (mCRPC) treated with abiraterone acetate and prednisone (AAP)." (2018): LBA5009-LBA5009.

Related Content: ASCO GU 2021: Multi-Institutional Evaluation of the Clinical Outcomes and Genomic Correlates of African Americans with Metastatic Castration-Sensitive Prostate Cancer