The Oncotype DX AR-V7 Nucleus Detect assay was specifically designed to guide treatment decisions in metastatic castration-resistant prostate cancer (mCRPC) patients who have recieved and failed an androgen receptor (AR) targeted therapy. This test has been validated in a large clinical cohort from multiple studies and is the only clinically validated assay proven to detect resistance to AR-targeted therapies (such as abiraterone (Xytiga®), enzalutamide (Xtandi®), and apalutamide (Erleada®)) in mCRPC patients.
Clinical studies found that Nuclear AR-V7+ patients do not benefit from AR-targeted therapies
Study 1: Nuclear AR-V7 presence predicts lack of effectiveness of AR-targeted therapies1
A study published in JAMA Oncology from Memorial Sloan Kettering Cancer Center demonstrated that mCRPC patients with AR-V7+ circulating tumor cells (CTCs) experience faster progression and lower median overall survival when compared to mCRPC patients with AR-V7- CTCs. The presence of AR-V7 protein in the nucleus signals resistance to continued AR-targeted therapies and is associated with rapid disease progression and shorter cancer-specific survival. This suggests that patients with detectable blood levels of AR-V7 should consider life-prolonging chemotherapy as an alternative to potentially less effective and more expensive hormonal treatment with AR-targeted therapies.
In the chart below, note that all patients who were nuclear AR-V7+ and treated with an AR-targeted therapy progressed to end stage within 12 months, underscoring lack of efficacy of AR-targeted therapies in this patient population.
AR-V7+ patients treated with AR-targeted therapies had significantly reduced overall survival2*
Study 2: Nuclear-specific localized AR-V7 protein can help identify patients who may live longer based on therapy selection (taxane chemotherapy vs AR-targeted therapy)2
A second study published 2018 in JAMA Oncology found that nuclear AR-V7 status in CTCs and treatment type were associated with overall survival in mCRPC patients. Patients who were AR-V7+ had superior overall survival with taxane therapy over AR-targeted therapies, while AR-V7- patients were found to have superior overall survival with AR-targeted therapy over taxanes.
As highlighted in the chart below, median overall survival for AR-V7 negative patients was 19.8 months on AR-Targeted therapy vs 12.8 months on taxanes. Whereas, median overall survival for AR-V7 positive patients was 14.3 months on taxanes vs 7.3 months on AR-Targeted therapy.
Androgen Receptor Splice Variant-7 (AR-V7), Therapy, and Overall Survival*
Patients had recieved and failed an AR-targeted therapy prior to this study
Study 3: Nuclear-specific localization of AR-V7 is required for accurate test results3
A 2016 study published European Urology analyzed outcomes for patients with mCRPC on AR-targeted therapies and standard chemotherapy. The authors found that patients who had nuclear AR-V7+ CTCs were likely to survive longer on taxane-based chemotherapy, whereas location agnostic AR-V7 expression (AR-V7 present in either nucleus, cytoplasm, or both) was less prognostic and not predictive of treatment response.