Androgen Receptor V7 Status Does Not Affect Response to Taxane Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

Selezionata da Pietro Cazzola

Proastate cencerFebruary 23, 2015 – Orlando, Florida – Findings from a small prospective study suggest that androgen receptor V7 (AR-V7) status does not significantly affect response to taxane chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Treatment outcomes were largely similar for the 17 patients with AR-V7-positive prostate cancer and the 20 patients with AR-V7-negative disease included in the analysis.
The results of this study were reported at the Genitourinary Cancers Symposium, held from February 26 to 28, 2015, in Orlando, Florida.
Emmanuel Antonarakis, MD, of Johns Hopkins University, Baltimore, Maryland, explained that AR-V7 is a truncated form of the androgen receptor (AR) that is detected in about a third of patients with castration-resistant prostate cancer. A recent clinical study by Dr. Antonarakis and colleagues showed that mCRPC in men who had AR-V7 in circulating tumor cells was resistant to the hormonal drugs enzalutamide and abiraterone. In addition, prior research in prostate cancer mouse models has also linked AR-V7 with resistance to taxane chemotherapy. The current study was carried out to determine whether these findings form preclinical experiments would be validated in patients with mCRPC.
Given that AR-V7 has been associated with resistance to hormonal therapy but not chemotherapy, the authors speculated that AR-V7-positive patients should probably be offered chemotherapy rather than hormonal therapy as initial treatment for mCRPC. Patients who are AR-v7-negative, however, can safely choose either regimen.
Study participants had comparable responses to therapy irrespective of AR-V7 status. Prostate-specific antigen (PSA) responses were achieved in 41% of AR-V7-positive men and 65% of AR-V7-negative men (difference not statistically significant). This 41% PSA response rate to taxane therapy was notable because the PSA response rate to abiraterone or enzalutamide in AR-V7-positive patients was 0% in the authors’ prior study.
The median progression-free survival with taxane therapy was also comparable in AR-V7-positive (5.1 months) and AR-V7-negative men (6.9 months; difference not statistically significant).
The AR-V7 abnormality occurs more frequently among patients who have undergone multiple lines of hormone therapies. Scientists believe that the AR-V7 abnormality is triggered by chronic low testosterone levels and may be an adaptive response of the cancer to maintain AR signaling when normal AR is inhibited.
Dr. Antonarakis concluded, “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. AR=V7 testing may be extremely valuable in guiding treatment decisions for men with hormone-resistant disease in the near future.”