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ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).
But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.
“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,
Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.
The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).
For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.
When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.
“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.
He noted that there is currently no commercial assay for AR-V7.
ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).
But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.
“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,
Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.
The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).
For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.
When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.
“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.
He noted that there is currently no commercial assay for AR-V7.
ORLANDO – The variant, labeled AR-47, is a truncated form of the androgen receptor that is missing the ligand-binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone (Zytiga) and enzalutamide (Xtandi) normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC).
But a study of circulating tumor cells (CTCs) from 37 men with mCRPC shows that patients whose tumor cells are positive for AR-V7 retain their sensitivity to taxanes.
“In this particular study, there was a 41% response rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or enzalutamide in this setting,” said Dr. Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore,
Dr. Antonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Testing for the presence of AR-V7 could in the future help guide clinicians when choosing therapies for men with mCRPC, Dr. Antonarakis said.
The investigators used a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel (Taxotere) or cabazitaxel (Jevtana).
For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) of men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -negative men was not significant.
When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = .003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide.
“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, before the data become clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial,” Dr. Antonarakis said.
He noted that there is currently no commercial assay for AR-V7.
AT THE GENITOURINARY CANCERS SYMPOSIUM
Key clinical point: The AR-V7 variant appears to confer resistance to abiraterone and enzalutamide, but not to taxanes.
Major finding: There was no significant difference in PSA response rates to taxanes among men who were positive or negative for the AR-V7 variant.
Data source: Study of 37 men with mCRPC treated with taxanes, and 62 treated with androgen receptor antagonists.
Disclosures: The study was supported by the Prostate Cancer Foundation. Dr. Antonarakis disclosed a consulting or advisory role with Sanofi, Dendreon, and Medivation, as well as travel, accommodations, and expenses, and honoraria from Sanofi, Dendreon, and Medivation.
