AR splice variant predicts resistance to PCa treatments

Metastatic castration-resistant prostate cancer patients whose tumors contain the androgen receptor (AR)-V7 splice variant are less likely to respond to enzalutamide (XTANDI) and abiraterone acetate (ZYTIGA), recent study results indicate.

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The study, which was published online ahead of print in the New England Journal of Medicine (Sept. 3, 2014), evaluated two groups of 31 men with metastatic castration-resistant prostate cancer and whose PSA levels were still rising despite low testosterone levels. Investigators gave each man either enzalutamide or abiraterone and tracked their PSA levels.

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.

Dr. Antonarakis“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 sooner, saving time and money while avoiding futile therapy,” said first author Emmanual Antonarakis, MD, of Johns Hopkins University, Baltimore, in a press release from that institution.

Senior author Jun Luo, PhD, of Johns Hopkins University, who first identified AR-V7 in 2007, and Dr. Antonarakis also evaluated patients’ progression-free survival (PFS) and overall survival (OS). They found that, in men receiving enzalutamide, PFS was 2.1 months in AR-V7-positive patients and 6.1 months in AR-V7-negative patients, while OS was 5.5 months in AR-V7-positive men and up to 9 months in AR-V7-negative men.

Similarly, in men receiving abiraterone, PFS was 2.3 months in AR-V7-positive patients and up to 6 months in AR-V7-negative patients, while OS was 10.6 months in AR-V7-positive men and up to 12 months in AR-V7-negative men.

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