Expert Emphasizes Inclusivity in Prostate Cancer Trials

Daniel J. George, MD

African-American men with metastatic castration-resistant prostate cancer (mCRPC) who received abiraterone acetate (Zytiga) plus prednisone in the Abi Race trial showed a longer median time to prostate-specific antigen (PSA) worsening than Caucasian patients.

Lead author Daniel J. George, MD, said that these results suggest that African-American men may experience greater benefit from chemotherapy and hormone-targeting treatment than Caucasians with mCRPC.

African-American patients are at a higher risk of developing and dying from prostate cancer, with an incidence rate of 60% in the United States, explained George. Additionally, these men are typically diagnosed later, which reflects the disparities in healthcare for African-American patients in general.

In the study, the rate of decline in PSA levels also was greater for African-American patients than for Caucasians at 82% versus 78%, respectively, for a greater than 30% decline; 74% versus 66%, greater than 50%; and 48% versus 38%, greater than 90%.

“This is incredibly important; we need to recognize that African-American patients want to be part of clinical trials,” said George. “We need to write the studies for them to make a difference.”

OncLive: Can you provide some background on the rationale for the Abi Race study?

In an interview with OncLive, George, a medical oncologist at Duke Cancer Center, discussed the findings from Abi Race and the implications they have on clinical trials in prostate cancer moving forward.George: In the United States, African-American men are not only at higher risk for developing prostate cancer, but they are at a much higher risk of dying from prostate cancer. In fact, they have a 2.5 times greater likelihood of death from prostate cancer than Caucasian men and are 5 times more likely to die from prostate cancer than Asian-American men.

What were the results?

We suspect that there is a genetic component to this, although there is access to care and other issues. When we look at our clinical trials in advanced prostate cancer, particularly abiraterone acetate in the COUGAR-AA-302 study, African-American men were very underrepresented. Because it was a global study, only 2.6% of men were African American—that is 28 men out of a study of 11,000.[In COUGAR-AA-302], of those 28 men, 15 had received abiraterone acetate and did better with higher response rates and longer responses by PSA. However, it was only 15 men. Therefore, we looked retrospectively at our own series at Duke Cancer Center and did a nested case control study with a 2:1 ratio of Caucasian versus African American, and we controlled for prior chemotherapy.

Guess what we saw? Exactly the same pattern—a higher PSA response rate and a longer time to PSA progression with the African-American men. From here, we wanted to do a prospective study.

We started this at Duke Cancer Center as a prospective study, and we made it a multicenter parallel-group study of 100 patients—50 African Americans and 50 Caucasians—to explore the differences in outcomes associated with race on the same treatment at the same centers. Over the period of this study, we found that African-American men, again, had a better PSA response rate at every cut-point that we looked at. Also, there was 40% longer time to PSA progression compared with Caucasian men. These are at the same centers with patients who have the same disease stage.

African-American men had higher rates of hyperglycemia, hypertension, and hypercholesterolemia going into the study. However, interestingly, they had higher rates of hypertension and hypokalemia, which are on-target effects of abiraterone acetate, which causes hypokalemia by lowering the adrenal gland function. We hypothesized that in African-American men, their tissues get greater exposure of abiraterone acetate than Caucasian men. That is why this drug may actually be working better in that population.

This was not across the board. One area that we did not see a difference in is radiographic progression-free survival. For both groups, it was about 16 months. However, this study was not powered to do a head-to-head comparison. It is possible that there is a difference there, if we did a larger study. In the end, these results tell us that it is feasible to do race-based studies; we absolutely can accrue these patients to clinical trials.

There are differences when you do race-based studies, both in terms of the clinical efficacy as well as the side effects. We need to do these kinds of studies. Importantly, we need to understand this beyond race. It is not skin color; it is the genes associated with skin color. We need to understand what those genetic factors are. We have blood samples on all of these patients, so we can now begin to look at the genetic factors associated with androgen transport and abiraterone transport to see if our theory holds up.

Going forward, how should the factor of race should be used?

In the future, the FDA and other regulatory agencies are going to need to mandate, postapproval, that these patients are studied, so we understand if there are differences by race.Race is a factor—it is not the only factor—but we need to understand beyond self-described race. What is it about the makeup of African ancestry? We will be looking at single nucleotide polymorphisms, and then we want to look at certain pathways and genes. It is important for us to understand that there are germline factors that are inherited that do affect the long-term response to therapies in prostate cancer, as well as prognosis.

George DJ, Heath EI, Sartor, AO, 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). J Clin Oncol. 2018;36 (suppl; abstr LBA5009).