mCRPC agent’s efficacy differs depending on race

October 11, 2018
Cheryl Guttman Krader, BS, Pharm

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Both the efficacy and safety of abiraterone acetate (ZYTIGA) treatment for metastatic castrate-resistant prostate cancer (mCRPC) appear to differ depending on race, according to results of Abi Race, a prospective, multicenter trial presented at the American Society of Clinical Oncology annual meeting in Chicago.

Chicago-Both the efficacy and safety of abiraterone acetate (ZYTIGA) treatment for metastatic castrate-resistant prostate cancer (mCRPC) appear to differ depending on race, according to results of Abi Race, a prospective, multicenter trial presented at the American Society of Clinical Oncology annual meeting in Chicago.

The parallel group study included 50 African-American and 50 Caucasian patients with no history of chemotherapy for CRPC who were treated with abiraterone, 1,000 mg daily, plus prednisone, 5 mg twice daily. Radiographic progression-free survival (rPFS) was analyzed as the primary endpoint, and the median values did not differ significantly between the African-American and Caucasian patient groups (16.7 vs. 16.5 months).

Also see: Rethinking race and prostate cancer outcomes

Secondary endpoint analyses showed that PSA response rates were numerically greater in African-American men than in Caucasians whether considering a PSA decline ≥30% (82% vs. 78%), ≥50% (74% vs. 66%), or ≥90% (48% vs. 38%). In addition, Kaplan-Meier analysis showed the PSA response was more durable in the African-American versus Caucasian patient group (median PSA PFS, 16.6 vs. 11.5 months). Differences between the two study groups were also seen in rates of several adverse events of special interest that are associated with adrenal gland function, with hypertension, hyperglycemia, hypokalemia, and hypomagnesemia occurring more often in African-Americans than in Caucasians.

Speaking with Urology Times, senior author Daniel J. George, MD, highlighted the importance of conducting prostate cancer studies to characterize outcomes in African-American patients and shared some take-home messages from Abi Race.

“We know that black men have a 2.5-fold greater likelihood of dying from prostate cancer than white men, and so we need to have a focus on black men if we are going to identify strategies that will have a positive impact on prostate cancer-related mortality. Unfortunately, black men have been very underrepresented in phase III studies of prostate cancer treatments,” said Dr. George, professor of medicine at Duke Cancer Institute, Durham, NC.

“Although it was believed that accrual of black patients into prospective prostate cancer studies would be extremely difficult, Abi Race shows otherwise, and the findings pointing to potential race-related differences in efficacy and treatment-related side effects indicates the research is important.”

Next:Further studies neededFurther studies needed

Alicia K. Morgans, MD, MPH, reviewed the study in a discussion session. She noted that the difference between study groups in PSA PFS did not achieve statistical significance because of insufficient power.

“Further studies including more men are needed to prove that the response to abiraterone differs by race,” said Dr. Morgans, associate professor of medicine, Northwestern University Feinberg School of Medicine, Chicago.

“Differences in androgen transport genes and possibly drug metabolism and other genes may be driving differences in outcomes and toxicity profiles with abiraterone treatment. We know that patient-centered care can improve outcomes, making these important issues to investigate as we try to personalize therapy for patients.”

Interest in conducting a prospective study to investigate racial differences in response to abiraterone for chemotherapy-naïve men with mCRPC arose from findings of a post-hoc analysis of data in the pivotal COUGAR-AA-302 trial that showed African-American men had a higher PSA 90% response rate and longer median rPFS compared with the overall population.

“It is noteworthy that the median PSA progression-free survival for the Caucasian men in Abi Race was very similar to the 11.1 months reported in COUGAR-AA-302 in which only 2.6% of the study population was black,” said Dr. George.

Read: African-Americans fare well with chemo for PCa

Investigating the potential race-related difference in outcomes, Dr. George and colleagues conducted a retrospective case-controlled study of men treated with abiraterone and prednisone at their center and again found higher PSA response rates among African-American men compared with Caucasians who were matched for prior chemotherapy.

Meanwhile, it was found in a study investigating abiraterone prior to prostatectomy that higher intracellular concentrations of the drug were achieved in patients with single nucleotide polymorphisms (SNPs) in certain SLCO proteins.

“SLCOs are involved in cellular uptake of steroid hormones, including abiraterone and testosterone, and so these findings suggested there may be a genetic basis for differences in abiraterone efficacy and safety,” Dr. George said.

Therefore, Abi Race is also investigating germline SNPs by race. Results from analyses completed so far show differences between groups in the proportions of patients with certain SNPs in SLCOs.

“It is critical to recognize that it is genetics that track with differences in efficacy and safety rather than race or skin color per se. We hope that this prospective study will allow us to identify some of those genetic factors,” Dr. George said.

“The next step might be to use the information to identify populations where abiraterone might even be used early in a curative setting.”

Additional genetic analyses are ongoing and a follow-up study is underway. Known as PANTHER, the new prospective trial is investigating treatment with abiraterone and apalutamide (Erleada) in parallel groups of African-American and Caucasian patients with mCRPC.

Dr. George is a consultant to and receives research funding from Janssen/Janssen Oncology. Dr. Morgans is a consultant to and receives honoraria from Janssen. For full disclosures, see bit.ly/AbiRace.