Unexpected Race-Based Findings in Novel Prostate Cancer Study

Black men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (Zytiga) plus prednisone had similar survival outcomes but more toxicity compared with white men, a multicenter prospective study showed.

Median radiographic progression-free survival (PFS), the study’s primary outcome, was similar between the two groups, at 16.6 and 16.8 months for the Black and white patients, respectively, reported Daniel George, MD, of Duke University Medical Center in Durham, North Carolina, and colleagues.

And median overall survival was nearly identical (35.9 vs 35.7 months, respectively). In addition, Black men had a median time to prostate-specific antigen (PSA) progression (TTP) of 16.6 months compared with 11.5 months for white men, as shown in the team’s study in Cancer.

“To our knowledge, our study is the first interventional trial in mCRPC to prespecify parallel patient treatment groups by self-identified race and to evaluate clinical efficacy and safety outcomes prospectively by race,” the researchers wrote.

They noted that Black men are more likely to develop prostate cancer at an earlier age, present with advanced‐stage disease, have a greater risk of early biochemical recurrence and metastasis, and have a shorter cancer‐specific survival.

“But Black Americans are really underrepresented in prostate cancer clinical trials, particularly in the studies that lead to FDA registration,” George told MedPage Today. “We need to do a better job of accruing these patients, and one of the reasons may be differences in how these drugs affect patients by their genetic diversity, and consequently by race.”

Combined abiraterone and prednisone was approved by the FDA in 2011 for men with mCRPC based on the results of the Cougar 302 trial, but only 3.6% of the patients in that study were Black. A retrospective analysis of the trial, which George co-authored, showed a trend of Black patients having a longer TTP and greater PSA response, he noted.

“And then we looked at this retrospectively with our own clinical experience at Duke, and saw the same trends when we matched [the Black patients] to white patients. So we wanted to look at this prospectively,” George said.

A direct comparison of outcomes between the two sets of patients would have required a phase III trial of considerable size. Instead, George and his colleagues performed a prospective, multicenter study of abiraterone acetate plus prednisone treatment of 50 Black men and 50 white men who had mCRPC to both demonstrate that it is feasible to enroll an equal percentage of Blacks and whites and to see whether the trends seen in the retrospective analysis would be reproduced.

The primary end point was radiographic PFS based on Prostate Cancer Working Group 2 criteria. Secondary end points included various PSA kinetics such as the estimation of the percentage of men who achieved PSA declines of 30%, 50%, or 90% from baseline.

The estimated rates of PSA decline from baseline in the study were 82%, 74%, and 48%, respectively, for Black men, and 78%, 66%, and 38% for white men, the researchers reported.

“What we were surprised at was not this trend in PSA response, which we have seen before, but that there were actual differences in toxicity and side effect profiles that correlated with race, that had not been seen before,” George said.

Specifically, there were greater rates and severity of adverse events related to adrenal hormone suppression in the Black men compared with white men. For example, there was a substantial difference in grade 3 and 4 rates of hypertension between Black men (24%) and white men (16%).

Estimated rates of hypokalemia (34% and 20%) and hypomagnesemia (16% and 8%) also differed in Black men and white men, and more severe grade 3 and 4 rates of hypokalemia were more frequent in the Black men — 12% versus 4% for the white men.

If the results are confirmed, the findings could support having different thresholds for monitoring and managing adverse events in Blacks versus white patients, George and co-authors said. They noted that newer trials evaluating abiraterone plus prednisone in mCRPC have been using a lower starting dose of prednisone (5 mg daily rather than 5 mg twice daily).

“That may be insufficient, however, to compensate for the adrenal suppression that this drug causes in black patients,” said George. “So it will be really important to look in some of these earlier disease settings, where we use these lower doses of prednisone, to see if the toxicity seen in Black patients is even higher.”

The new study also shows it is possible to enroll a representative number of Black patients into prostate cancer trials, George said. “And it reinforces why it is important to have these patients represented in clinical trials, and why genetic diversity is a good thing in clinical trials, rather than having our studies populated by a more limited genetic pool.”

The study also shows, he added, that Black men with prostate cancer fare just as well as white men, even with accompanying health issues, suggesting that future trials should enroll Black patients who might otherwise be excluded because of disqualifying health conditions.