Prostate Tumor Androgen Receptor Abnormality Not Associated with Taxane Resistance

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Androgen receptor V7 (AR-V7) status does not predict response to taxane chemotherapy in mCRPC.
Androgen receptor V7 (AR-V7) status does not predict response to taxane chemotherapy in mCRPC.

ORLANDO—Androgen receptor V7 (AR-V7) status in circulating tumor cells (CTCs) does not predict response to taxane chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC), according to a small prospective study (Abstract 138) presented during the 2015 Genitourinary Cancers Symposium.1

The study authors had previously shown that AR-V7 status helps predict mCRPC outcome following treatment with enzalutamide or abiraterone. But that wasn't the case with taxanes; PSA progression-free survival (PFS) was not significantly different between men with AR-V7 positive and negative status, following taxane therapy (4.5 months vs. 6.2 months, respectively; P=0.32, not significant), according to lead study author Emmanuel Antonarakis, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine in Baltimore, MD.

The study included 47 men with mCRPC.

“Detection of AR-V7 in CTCs from men with mCRPC is not associated with primary resistance to taxane chemotherapy,” reported Dr. Antonarakis. “AR-V7-positive patients may retain sensitivity to taxanes and in these men taxanes might possibly be more efficacious than AR-directed agents.”

Among men with AR-V7-negative CTCs, taxanes “appear to have comparable efficacy to AR-directed agent,” Dr. Antonarakis reported. The study was the first clinical trial exploration of a possible association between AR-V7 status and taxane treatment outcomes among men with prostate cancer.

AR-V7 is an androgen receptor abnormality that has been shown to be associated with resistance to hormone treatments enzalutamide and abiraterone.

AR-V7 abnormality occurs in approximately a third of men with castration-resistant prostate cancer. It is more common among men who have undergone multiple lines of hormone therapies, and may be triggered by chronic low testosterone levels, representing an adaptive tumor response to maintain androgen receptor signaling even after normal signaling has been inhibited.

The study was not a randomized trial and confirmation still awaits larger biomarker-driven studies that randomly assign patients to taxane chemotherapy versus AR-directed therapy, Dr. Antonarakis cautioned.

RELATED: In Metastatic Prostate Cancer, Radiographic PFS Associated with Survival

But if the findings are confirmed, AR-V7 might be a biomarker for treatment selection for mCRPC, he said.

“We urgently need markers to predict which therapies are going to be effective and which will not be effective in individual patients with advanced prostate cancer,” reported Dr. Antonarakis. 

Despite the negative findings for predicting taxane-treatment outcomes, AR-V7 may yet prove to be “extremely valuable in guiding treatment decisions for men with hormone-resistant disease in the near future,” Dr. Antonarakis said.

The study was funded by the Prostate Cancer Foundation.

Reference

  1. Antonarakis ES, Lu C, Chen Y, et al. AR splice variant 7 (AR-V7) and response to taxanes in men with metastatic castration-resistant prostate cancer (mCRPC). 2015 Genitourinary Cancers Symposium. Abstract 138.

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