CHICAGO-African-American men are known for having the highest risk of being diagnosed with and dying from prostate cancer (SEER Cancer Stat Facts). Yet, a prospective clinical trial showed that when Caucasian and African-American men with metastatic castration-resistant prostate cancer were treated with abiraterone acetate plus prednisone, African-American men had the same, perhaps even better outcomes. Results from the study were reported at the 2018 ASCO Annual Meeting (Abstract LBA5009).
"These are, to my knowledge, the first data suggesting that there might be a differential response between black and white men, such that black men respond even better," said Neha Vapiwala, MD, Associate Professor of Radiation Oncology at the Hospital of the University of Pennsylvania, Philadelphia. "It's not the first time we've seen racial differences. [For example], there are certain blood pressure medications that are preferred or not preferred in certain ethnic groups."
These findings are similar to the results of a retrospective analysis of nine randomized phase III trials also reported at ASCO (Abstract LBA5005). The study authors found that African-American men and Caucasian men with metastatic castration-resistant prostate cancer had the same overall survival when treated with docetaxel plus prednisone.
Trial Design
The Abi Race trial was a prospective, open-label, multicenter study, and 100 men with metastatic castration-resistant prostate cancer were enrolled (NCT01940276). Of the study participants, 50 self-identified as African-American and 50 as Caucasian. All participants were chemotherapy-naive. Participants received standard of care abiraterone acetate plus prednisone until disease progression or unacceptable adverse events. The primary endpoint was radiographic progression-free survival (PFS), and secondary endpoints included prostate-specific antigen (PSA) kinetics and safety.
About the African American group and Caucasian group, the lead study author Daniel George, MD, Professor of Medicine and Surgery at Duke University, Durham, N.C., described them as "very similar." Participants had a median age of 69 years and median PSA level at enrollment of 22. Gleason scores were also similar between groups with 28 participants in each group having a Gleason score of at least 6.
Of note, there were a few differences between the groups. The African-American group had higher rates of hypertension, hyperglycemia, and hypercholesterolemia, which George said would have excluded these participants from large prospective phase III trials. Also, prior treatment with immunotherapeutic sipuleucel-T was more common among Caucasian participants than African-American participants (40% vs. 24%).
"It's interesting that the white patients had a higher percentage of sipuleucel-T use," said George. "Sipuleucel-T is one of the therapies that we think there may also be a difference in outcome associated with race."
Reported Findings
The African-American and Caucasian groups had a similar median radiographic PFS, 16.7 months for African-American men and 16.5 months for Caucasian men. This finding aligned with the COU-AA-302 trial, which showed a median radiographic PFS of 16.5 months for participants in the abiraterone acetate plus prednisone arm (NEJM 2012;368(2):138-148).
"Importantly, African-Americans didn't show any trend to a worse outcome, as we might have expected from that higher rate of death from prostate cancer," said George. "I think a larger study would be necessary to show any statistical difference between these populations."
Median PSA PFS was longer for African-American men compared with Caucasian men (16.6 months vs. 11.5 months), and this effect was seen at every PSA decline threshold: 30 percent or more, 50 percent or more, and 90 percent or more PSA decline. George noted that the median PSA PFS was "very similar" to what was seen in the COU-AA-302 study for the overall study population.
"As with most of these drugs that we use in prostate cancer, we don't always get similar responses for all the different biomarkers, so for example, with PSA, some treatments impact that more directly than others, and certainly here it looks like there was a more dramatic percentage decline," said Vapiwala. However, she asserted, "At the end of the day, it doesn't mean much if [PSA decline] doesn't translate into either radiographic progression-free survival improvements or ultimately overall survival improvements because, what you're trying to measure is not PSA going up and down, but ultimately how that then predicts for new lesions in the bone, new sites of disease, or deaths from that disease."
However, Vapiwala said the PSA finding does raise a question for why that may be and what other differences there may be in response to other therapies based on race.
"[Among African-American participants], we even saw a much greater rate of what we call a tumor flare, where new lesions appear while the PSA is declining, suggesting there might be a different biologic response to this therapy in African-American patients versus Caucasian patients," said George. Sixteen percent of African-American participants had tumor flare compared to 4 percent of Caucasian participants.
There were also differences between the groups for toxicity. The African-American group had higher rates of constipation, hyperglycemia, hypokalemia, and hot flashes. In contrast, the Caucasian group had higher rates of vomiting, fatigue, headache, and cough.
The researcher investigated whether there could be differences in genotype and single-nucleotide polymorphisms that could be a biological explanation for differences and found distinct genotypic clustering between African-American and Caucasian men.
Implications & Takeaways
George noted several key takeaways from the study. First, he noted studies done by racial groups are possible despite the low incidence in national or international studies.
Alicia Morgans, MD, Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine, echoed this view, saying "Inclusion of a representative number of African-American men in mCRPC trials is feasible. This study took 10 sites and nearly 3 years, but it was absolutely feasible."
George also noted that these studies "absolutely" need to be done because there are differences in both outcomes of treatment as well as side effects that could have significant implications in how these drugs are used. Lastly, he said, "There are genetic differences underlying race and we need to understand what those are and how they correspond with these outcomes."
Christina Bennett is a contributing writer.