For patients with castration-resistant prostate cancer, detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells appears to be associated with enzalutamide and abiraterone resistance, according to a study published in the New England Journal of Medicine.
Emmanuel S. Antonarakis, M.D., from the Johns Hopkins University School of Medicine in Baltimore, and colleagues used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from men with metastatic castration-resistant prostate cancer. A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled.
The researchers found that 39 and 19 percent of the enzalutamide- and abiraterone-treated patients, respectively, had detectable AR-V7 in circulating tumor cells. AR-V7-positive enzalutamide-treated patients had lower prostate-specific antigen (PSA) response rates than AR-V7-negative patients (0 versus 53 percent; P = 0.004).
In addition, these patients had shorter PSA progression-free survival, clinical or radiographic progression-free survival, and overall survival. Similar results were seen for abiraterone-treated AR-V7-positive versus negative patients. After adjustment for expression of full-length androgen receptor messenger RNA, the correlation between AR-V7 detection and therapeutic resistance was maintained.
“Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone,” the authors write. “These findings require large-scale prospective validation.”