ASCO 2021: Differences in Toxicity and Outcomes: A Race-based Case Study

( As part of the 2021 American Society of Clinical Oncology Annual Meeting, a session entitled “Minority Enrollment in Cancer Clinical Trials”. Within this session, Dr. Daniel George presented on Differences in Toxicity and Outcomes utilizing a Race-based Case Study.

Dr. George began by highlighting that prostate cancer is one of the conditions with the greatest racial disparities. Both the number of new cases per 100,000 persons and number of death pre 100,000 persons attributable to prostate cancer are dramatically higher among Black men, with approximately 85 more cases per 100,000 persons (60% greater likelihood) and approximately 30 more deaths per 100,000 persons among Black individuals (more than two-fold higher) compared to white. These disparities are even greater when Black men are compared to men of other, non-white ethnicities.


Dr. George emphasized that these disparities are largely driven by health care access disparities and socioeconomic factors, though there are also biological characteristics that may contribute.

Among the many agents which have been approved in the treatment of patients with advanced prostate cancer over the past decade, he then transitioned to discussing abiraterone acetate which was initially approved in men with metastatic castration-resistant prostate cancer following docetaxel chemotherapy (COU-301) but has subsequently been approved both in metastatic castration-resistant disease prior to chemotherapy (COU-302) and in metastatic castration sensitive disease (LATITUDE and STAMPEDE). Abiraterone is administered concurrently with oral steroids to prevent mineralocorticoid excess. In spite of this, the common adverse events relate to mineralocorticoid excess, including fluid retention, hypokalemia, and hypertension.

The question arose as to whether Black men may respond better to abiraterone acetate than white men. Unfortunately, in this trial which enrolled 1088 patients (546 randomized to abiraterone acetate and 542 randomized to placebo), only 28 were Black men (15 randomized to abiraterone acetate and 13 randomized to placebo). While these small sample sizes precluded formal analyses, there was a suggestion that the proportion of patients with a 90% of greater decline in PSA levels may be higher among Black men than the overall population (53% vs 31%) receiving abiraterone. Further, the median time to PSA progression was longer in Black men receiving abiraterone acetate (16.6 months vs 11.1 months). These data fomented the hypothesis that Black men may have better outcomes.

This led to a case-control analysis at Duke among patients treated with abiraterone. This demonstrated that African American patients were more likely to have > 30%, > 50%, and > 90% PSA declines and were less likely to have no PSA decline with therapy.


These data together formed the basis of a prospective evaluation of this question, designed as a prospective parallel-group trial of abiraterone by race. This study was performed among men with chemotherapy naïve metastatic castration-resistant prostate cancer. A total of 100 men were enrolled, with a planned stratification according to self-described race of 50 Black men and 50 White men who all received treatment with abiraterone acetate 1000mg orally daily in addition to prednisone 5mg orally twice daily.


Moving forward, the authors sought to determine whether there were differences in disease progression or adverse events. Dr. George emphasized that this was not designed as a head-to-head comparison of outcomes, but rather as a parallel-group study to characterize the following outcomes in both Black and White men: radiographic progression-free survival. PSA kinetics, overall survival, and safety (adverse event rate and severity), as well as to explore GWAS associated with ancestry and outcomes.

The authors assumed that the study would be easy to accrue given that it would provide free access to a standard of care therapy; that Black men would be more difficult to accrue; that Black men would screen fail more often; that community sites with higher representation of Black patients would accrue better; and that race would not affect toxicity.

In the first year, they accrued only 7 patients within their cancer system. Other studies published in a similar time demonstrated difficulty accruing Black patients leading to premature study closure. Instead of taking this approach, Dr. George and colleagues expanded this study to a number of other sites and, subsequently, successfully increased accrual.

Notably, they were able to successfully accrue equally among both Black and White men, despite Black men comprising between 20 and 40% of the clinical populations at the centers where the trial was open.


Further, contrary to the hypothesis, there was no difference in screen failures between Black and White men, despite higher rates of comorbidity among the Black men. The vast majority of patients were accrued from academic, rather than community, sites.

In terms of oncologic outcomes, the authors demonstrated no difference in radiographic progression-free survival or overall survival on the basis of race. Further, the median rPFS and OS were comparable to the randomized COU-302 trial. Interestingly, Black men had longer time to PSA progression (16.6 months vs 11.1 months).


In keeping with the hypothesis-generating data from the COU-302 cohort, PSA responses were higher among Black men than white men. Most notably, undetectable PSA levels were found more commonly in Black men (PSA <0.1 ng/mL: 18% (95% CI 10-30%) among Black men and 8% (95% CI 2-20%) among white men).

However, they did find differences in toxicity according to race: hypertension, hypokalemia, and hyperglycemia were more common in Black men, suggesting differential effects on adrenal function.

Considered in total, nearly every one of the assumptions leading into the trial were proven to be untrue.

Presented by: Daniel George, MD, Medical Oncologist, Duke Cancer Institute, Durham, NC

Written by: Christopher J.D. Wallis, MD, Ph.D., Urologic Oncology Fellow, Vanderbilt University Medical Center, Twitter: @WallisCJD at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting #ASCO21, June, 4-8, 2021