Standard mCRPC Therapy May be More Beneficial to Black Men Than White Counterparts

Daniel J. George, MD

Duke researchers discussed findings from 2 studies at the 2018 ASCO Annual Meeting, which revealed chemotherapy and hormone-targeting treatment may be more beneficial to black men with metastatic castration-resistant prostate cancer (mCRPC) compared with their white counterparts. This new revelation underscores the need to ensure equal access to care and design racially inclusive clinical trials.

In the chemotherapy study, an analysis of pooled data from 9 randomized phase III trials indicated that black men treated with docetaxel (Taxotere) and prednisone had a 19% lower risk for death than white men who received the same therapy after adjusting for established risk factors.¹

In the Abi Race study, black men who received standard abiraterone acetate (Zytiga) plus prednisone therapy had a longer median time to PSA worsening than white participants (16.6 vs 11.5 months).²The rates of declines in prostate-specific antigen (PSA) levels also were greater for black patients than for white participants: 82% versus 78%, respectively, for a greater than 30% decline; 74% versus 66%, greater than 50%; and 48% versus 38%, greater than 90%.

The findings come at a time of continuing concern about health disparities between black and white men diagnosed with prostate cancer in the United States. The incidence rate of prostate cancer is 60% higher among black men and they are twice as likely to die from the disease as white men.^3,4Additionally, black men are typically diagnosed with prostate cancer at a later stage and have unequal access to healthcare, according to Susan Halabi, PhD, a professor of biostatistics and bioinformatics at Duke University in Durham, North Carolina, and lead author on the chemotherapy study.

Despite these differences in outcomes on a broad population basis, the studies showed that black patients with similar disease burden can benefit as much as white men if given the same therapies, noted Daniel George, MD, a professor of medicine and surgery at Duke and lead author on the abiraterone study. “It is reassuring to us that these patients can do well when given the standard therapies at the right time. Understanding genetically if they could do even better, and why, is a critical next step,” he said.

Both Halabi and George, who discussed their research during a press conference in advance of their presentations at the ASCO meeting, said the studies highlight a pressing need to enroll more minorities in clinical trials so that researchers can determine the reasons for differences in responses. “We need to do more biological and genomic studies to see if the differences are due to access to healthcare or if it is a biological difference,” said Halabi.

“What we need to be able to do is help educate clinicians out there that these patients need to be treated and they need to be treated aggressively with the standard-of-care therapies when they’re most appropriate,” said George. “When that happens and it’s really equal by race, we do see similar outcomes. That suggests to me that perhaps one of the reasons why we’re not seeing those similar outcomes on a population basis is because maybe there is a gap in terms of this treatment approach.”

Chemotherapy Findings

To compare responses by race, Halabi and colleagues analyzed data from 8820 men with chemotherapy-naïve mCRPC treated with docetaxel and prednisone alone or in combination with other therapies in clinical trials. In all, 85% of the participants were white and 6% were black. The study represents the largest analysis conducted thus far that compares black and white men with advanced prostate cancer treated with chemotherapy, Halabi said in a statement.

Overall, the median age of the participants was 69 years and 94% had performance status scores of 0 to 1. The median hemoglobin, PSA, and alkaline phosphatase (ALP) levels were 12.9 g/dL, 86 ng/mL, and 139 U/L, respectively. Seventy-two percent had bone disease with or without lymph nodes, 9% each had lung disease or liver disease, and 7% had lymph node—only involvement.

Investigators sought to examine the hypothesis that black men with advanced and lethal prostate cancer would have worse survival outcomes than white men, she said. Instead, they found that median OS for both black and white men was 21 months.

When researchers adjusted for prognostic factors such as patient age, performance status, site of metastasis, PSA level, ALP, and hemoglobin, they found that black men were less likely to die from any cause (HR, 0.81;P= .004).

“It could be that the differences are due to biological reasons or it could be that the African American patients are responding better to docetaxel/prednisone,” said Halabi. “This underscores the importance of enrolling minorities in clinical trials.”

Abiraterone Results

In the Abi Race study, researchers wanted to further investigate clues indicating that the small number of black men who participated in the COU-AA-302 study had better outcomes than the white patients. The study findings prompted the FDA to expand the approval of abiraterone in combination with prednisone for patients with chemotherapy-naïve mCRPC in 2012.

Only 28 of the 1088 patients in the study were black; 53.3% (n = 8) of the 15 black patients who received abiraterone achieved ≥90% PSA decline compared with 30.8% (n = 168) of the 546 white men who took the drug.⁵

In their pilot study, George and colleagues enrolled 100 men with mCRPC who had not received prior chemotherapy for CRPC and had a Karnofsky performance status ≥70. The population was evenly divided among men who self-identified as black or white. Overall, the median age was 68.5 years and 56% of participants had a Gleason score of 8 to 10. Baseline characteristics between the 2 groups were similar, the researchers said in their abstract.

Although black patients achieved higher rates of PSA decline and a longer interval to worsening of PSA, the median rate of radiographic progression-free survival was 16.7 months for the black patients and 16.5 months for the white patients.

Investigators plan to conduct molecular analyses of blood and tissue from samples collected from study participants. They also are co-leading the IRONMAN study, which seeks to establish an international cohort of at least 5000 men with advanced prostate cancer to collect data on treatment and outcomes (NCT03151629).

References

1. Halabi S, Dutta S, Tangen CM, et al. Overall survival between African-American (AA) and Caucasian (C) men with metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract LBA5005. meetinglibrary.asco.org/record/161601/abstract.
2. 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). Presented at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract LBA5009. meetinglibrary.asco.org/record/161843/abstract
3. Prostate cancer rates by race and ethnicity. Centers for Disease Control and Prevention website. www.cdc.gov/cancer/prostate/statistics/race.htm. Updated June 19, 2017. Accessed June 1, 2018.
4. SEER cancer stat facts: prostate cancer. National Cancer Institute website. seer.cancer.gov/statfacts/html/prost.html. Updated April 2018. Accessed June 1, 2018.
5. Efstathiou E, Deshpande H, George D, et al. An exploratory analysis of efficacy and safety of abiraterone acetate (AA) in black patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (ctx). Presented at: 2014 AACR Annual Meeting; April 5-9, 2014; San Diego, CA. Abstract CT313. cancerres.aacrjournals.org/content/74/19_Supplement/CT313.