Oncotype DX AR-V7 NUCLEUS DETECT

Clinical Evidence

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*

Survival Graph

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*

Survival Graph

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.

Survival Graph

REFERENCES

1. Scher, et al. JAMA Oncol. 2016.
2. Scher, et al. JAMA Oncol. 2018.
3. Scher, et al. Eur Urol. 2016.



a. DOI: 10.1001/jamaoncol.2016.1828
b. DOI: 10.1001/jamaoncol.2018.1621
 

Clinical Comparator Triala

A study assessing the validity of nuclear-localized androgen receptor being a predictive biomarker for castration-resistant prostate cancer

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Clinical Validation:
MSKb

A cross-sectional study at Memorial Sloan Kettering of 161 men with progressive mCRPC.

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