Prostate cancer patients whose tumors contain a shortened protein called AR-V7, which can be detected in the blood, are less likely to respond to two widely used drugs for metastatic prostate cancer, according to results of a study led by researchers at the Johns Hopkins Kimmel Cancer Center. If large-scale studies validate the findings, the investigators say men with detectable blood levels of AR-V7 should avoid these two drugs and instead take other drugs to treat their prostate cancer. A report on the work is described online in the New England Journal of Medicine.
The study evaluated two groups of men (31 men in total) with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.
Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80% of patients with metastatic prostate cancer, says study co-author Emmanuel Antonarakis, MD, but the drugs do not work in the remaining 20% of patients.
“Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy,” says Antonarakis. Read the study.
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