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Antiandrogen Resistance With AR-V7 in CRPC

Panelists: Raoul S. Concepcion, MD, Urology Associates; Kenneth Kernen, MD, Michigan Institute of Urology; Bryan A. Mehlhaff, MD, Oregon Urology Institute;
Published: Thursday, May 07, 2015
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Detection of the splice variant AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer (CRPC) may be associated with resistance to enzalutamide and abiraterone, according to a paper from Antonarakis and colleagues. In AR-V7–positive men, treatment with antiandrogen therapy did not improve PSA levels, progression-free survival (PFS), or overall survival (OS).

In the study, for men who were treated with enzalutamide (n = 31), those who were AR-V7–positive (39%) had shorter clinical or radiographic PFS (median 2.1 vs 6.1 months; P <.001) and OS (median 5.5 vs not reached; P = .002). Among men receiving abiraterone (n = 31), those who were AR-V7–positive (19%) also had shorter clinical or radiographic PFS (median 2.3 vs not reached; P <.001) and OS (median 10.6 months vs. not reached; P = .006).

Approximately, 10% to 20% of patients receiving abiraterone or enzalutamide do not experience a reduction in PSA level because of a preexisting splice variant, typically AR-V7, Neal D. Shore, MD notes. Various sequencing of therapies may increase the rate of non-response to 20% to 40%, indicating an acquired resistance. Research is in progress to better understand this resistance mechanism, Ganesh S. Palapattu, MD, notes.

Research is being done to identify alternative therapies for patients with AR-V7, notes Palapattu. Interestingly, AR-V7 is not a biomarker of response for chemotherapy in advanced CRPC. In 37 men who received chemotherapy, researchers found that regardless of AR-V7 status, there was not a significant difference in PSA response or in PFS.
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Detection of the splice variant AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer (CRPC) may be associated with resistance to enzalutamide and abiraterone, according to a paper from Antonarakis and colleagues. In AR-V7–positive men, treatment with antiandrogen therapy did not improve PSA levels, progression-free survival (PFS), or overall survival (OS).

In the study, for men who were treated with enzalutamide (n = 31), those who were AR-V7–positive (39%) had shorter clinical or radiographic PFS (median 2.1 vs 6.1 months; P <.001) and OS (median 5.5 vs not reached; P = .002). Among men receiving abiraterone (n = 31), those who were AR-V7–positive (19%) also had shorter clinical or radiographic PFS (median 2.3 vs not reached; P <.001) and OS (median 10.6 months vs. not reached; P = .006).

Approximately, 10% to 20% of patients receiving abiraterone or enzalutamide do not experience a reduction in PSA level because of a preexisting splice variant, typically AR-V7, Neal D. Shore, MD notes. Various sequencing of therapies may increase the rate of non-response to 20% to 40%, indicating an acquired resistance. Research is in progress to better understand this resistance mechanism, Ganesh S. Palapattu, MD, notes.

Research is being done to identify alternative therapies for patients with AR-V7, notes Palapattu. Interestingly, AR-V7 is not a biomarker of response for chemotherapy in advanced CRPC. In 37 men who received chemotherapy, researchers found that regardless of AR-V7 status, there was not a significant difference in PSA response or in PFS.
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