Study offers fresh insight into racial disparities in prostate cancer

Among patients with metastatic castration‐resistant prostate cancer (mCRPC) receiving abiraterone acetate (Zytiga) plus prednisone, survival outcomes were similar between Black and White men, while Black men trended toward higher declines in PSA and time to PSA progression (TTP), according to outcomes from a race-stratified prospective study.^1,2

Several other key findings emerged from the trial, including higher treatment toxicity in Black men and the identification of a potential biomarker of ancestry‐dependent treatment outcomes.

The open‐label study included 50 Black and 50 White patients with mCRPC enrolled at 10 sites. The investigators noted that to ensure that enrollment could be balanced by race, they did not exclude men with co-existing conditions, such as high blood pressure and diabetes, that have historically been among the exclusion criteria for prostate cancer trials.

In general, baseline characteristics were balanced between the White and Black patients cohorts; however, a history of diabetes was significantly higher among black men at 42% versus 10%, respectively. Rates of other comorbidities, including hypertension (88% vs 68%), hypercholesterolemia (42% vs 30%), and obesity (50% vs 44%), were also higher among Black men, but the rates were only modestly higher.

Despite these differences, survival outcomes were similar, regardless of race. The median radiographic progression‐free survival was 16.6 months among Black patients and 16.8 months among White patients. The median overall survival was 35.9 versus 35.7 months, respectively.

“When you look at the overall survival data for our study, they’re equal between Black and White men,” lead study author Daniel George, MD, professor in the departments of Medicine and Surgery at Duke University School of Medicine, stated in a press release. “But given the prevalence of coexisting conditions in the Black men we enrolled, mortality should have actually been higher for them.

“Our finding that it was not higher is telling—it suggests Black men with prostate cancer can fare just as well as whites, even with other health issues,” added George. “And it signals that future studies should consider enrolling Black men despite these often-disqualifying conditions.”

As has been previously observed in retrospective analyses, Black men had better declines in PSA and longer TTP. Among Black patients, 74% had a rate of PSA decline ≥50% compared with 66% among White patients. PSA declines to <0.2 ng/mL occurred in 26% and 10% of the patient populations, respectively. The TTP was 16.6 months among Black men compared with 11.5 months among White men.

Regarding safety, there were stronger signals for concern among Black men, including higher rates of grade 3/4 hypertension (24% vs 16%), hypokalemia (12% vs 4%), and hyperglycemia (10% and 4%). “If confirmed [in future research] these results could support different thresholds for monitoring and managing these important adverse events by race,” wrote George at al.

Through genetic analyses, George et al also identified SPHKAP/SPHK1 as potential biomarker of ancestry-dependent treatment outcomes with abiraterone/prednisone. The researchers believe that further investigation of this marker could facilitate understanding of why Black men seem to respond to hormone therapy more readily.

“We need to understand how genetic ancestry might affect treatment outcomes—especially disease responsiveness in prostate cancer—because we are now using and studying these therapies earlier in the disease where we have the opportunity to cure patients,” George stated in the press release.

“If there is a subgroup of patients with an ancestry-based predisposition for potential better response, we need to understand that. But to do so, we will need greater genetic diversity in our future study populations, especially among those with African ancestry. We aren’t going to fully understand this genetic complexity by solely enrolling men with European ancestry,” added George.

References

1. Study Confirms Racial Differences in Response to Prostate Cancer Treatment. Duke Health. Published online May 5, 2021. Accessed May 11, 2021. https://bit.ly/3fegH7k

2. George DJ, Halabi S, Heath EI, et al. A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer [published online ahead of print May 5, 2021]. Cancer. 2021 doi: 10.1002/cncr.33589