AR-V7 Assays and Treatment Outcomes in Castration-Resistant Prostate Cancer
Posted: Wednesday, May 15, 2019
According to the multicenter PROPHECY study, conducted by Andrew J. Armstrong, MD, of Duke University Medical Center, and colleagues, circulating tumor cell (CTC) androgen receptor splice variant 7 (AR-V7) may be a “strong predictor” of clinical outcomes in men with metastatic castration-resistant prostate cancer who are treated with abiraterone or enzalutamide. These findings, which were published in the Journal of Clinical Oncology, suggest that AR-V7 status may assist in treatment selection beyond prognosis and disease burden.
“Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter [progression-free and overall survival] with abiraterone or enzalutamide, and such men with [metastatic castration-resistant prostate cancer] should be offered alternative treatments,” the investigators concluded.
Of the 118 men in the study, 55 were treated with abiraterone, 58 were treated with enzalutamide, and 5 received both therapies concurrently. Baseline CTC AR-V7 levels were detected by two assays—the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay.
At baseline, 28 men tested AR-V7–positive, 88 were AR-V7–negative, and 2 were unevaluable by the Johns Hopkins assay. The Epic protein-based assay found 11 men to be AR-V7–positive, 96 were AR-V7–negative, and 11 were unevaluable.
After the investigators adjusted for CTC number and clinical prognostic factors, they found that detection of AR-V7 by both assays was independently associated with poorer outcomes. Specifically, AR-V7 detection was associated with hazard ratios of 1.9 for progression-free and 4.2 for overall survival with the Johns Hopkins assay. And, the hazard ratios linked to the Epic protein assay were 2.4 for progression-free and 3.5 for overall survival. In addition, fewer confirmed prostate-specific antigen or soft-tissue responses were observed in men with AR-V7–positive disease. The percentage agreement between the two assays was 82%.
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.