CTC AR-V7 Validated as Predictive Marker of Resistance to AR-Directed Therapy in mCRPC
Nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells (CTCs) is a predictive marker of shorter progression-free and overall survival (OS) with antiandrogen therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results from the phase III PROPHECY trial that were published in the Journal of Clinical Oncology.1
Results showed that AR-V7 in CTCs, according to 2 blood-based assays, is predictive of whether men with mCRPC have become resistant to androgen receptor (AR) inhibitors, such as enzalutamide (Xtandi) and abiraterone acetate (Zytiga), and have a low chance of benefiting from additional AR-driven therapy.
When evaluated with the Oncotype DX AR-V7 Nucleus Detect test and the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay, the median progression-free survival (PFS) for patients who were AR-V7 positive were shorter (HR, 2.4; 95% CI, 1.1-5.1; P = .020) and (HR, 1.9; 95% CI, 1.1-3.3; P = .032), respectively. Additionally, the OS through both assays were also associated with shorter OS outcomes (HR, 3.5; 95% CI, 1.6-8.1) and (HR, 4.2; 95% CI, 2.1-8.5), respectively, after adjusting for CTC number and clinical prognostic factors.
The findings suggest that AR-V7–positive patients with mCRPC should be treated with either taxane chemotherapy or enroll on a clinical trial with investigational therapy.