AR-V7 Liquid Biopsy Coming of Age

Once a man is castrate resistant and moves on a second line hormone therapy drug like Zytiga or Xtandi (aka AR inhibitors) it is inevitable that the Zytiga or Xtandi will also become ineffective.  

When this happens, the question that comes is what should be the next treatment?  Generally, the options currently available are either to move to the drug not initially used ( Zytiga if Xtandi was first used or Xtandi if Zytiga was used) or instead to use taxane chemotherapy (Taxotere aka docetaxel).  

Knowing which of these two options is best has been nothing but guesswork.  But, things are improving.  There is a test, not yet FDA approved,  that detects the expression of a protein called AR-V7 in the nuclei of circulating tumor cells taken from a vial of blood cells (liquid biopsy).  This test can help guide this decision.

A recent study (published in JAMA Oncology) evaluating this test has shown that a blood test can detect the protein called AR-V7 in circulating tumor cells and that the presence of this protein accurately predicts how well certain men will respond to AR inhibitors (Zytiga and Xtandi). 

This minimally invasive method, a blood draw, can screen a man’s blood for cancer cells that have broken free from a tumor and are circulating the bloodstream. By evaluating the presence of the AR-V7 protein, the cells can be analyzed to reveal how the prostate cancer may be progressing, responding to treatment or even if it will be sensitive to an AR Inhibitor.

The challenge answered by this study had been to prove that AR-V7 markers are reliable and can serve as a surrogate endpoint. 

The JAMA study provides proof that a liquid biopsy can accurately predict the best therapy choice for men whose disease has become resistant to an initial AR Inhibitor treatment.

“This test is an important advance in helping doctors and patients make treatment choices more confidently after frontline therapy no longer works,” said Memorial Sloan Kettering medical oncologist Howard Scher, who was the lead investigator for the study. 

The test focuses on the presence of a protein AR-V7 found in men with metastatic castration-resistant prostate cancer (mCRPC). The presence of this protein in the circulating tumor cells indicates the likelihood that an AR Inhibitor (Zytiga or Xtandi) will not be effective. 

Epic Sciences developed the test and Genomic Health distributes it, the Oncotype DX® AR-V7 Nucleus Detect™ test detects 

AR-V7 in CTCs in the bloodstream. The presence or absence of AR-V7 predicts how well the cancer will respond to AR Inhibitor drugs.

The 2016 research led by Dr. Scher from Memorial Sloane Kettering Hospital (MSK) provided preliminary evidence supporting     AR-V7 as a marker by using more traditional measures such as prostate specific antigen (PSA) levels and whether the cancer showed any progression.

This new study provides conclusive and independent validation of these findings by looking at how long men with mCRPC survived following second-line AR Inhibitor treatment with either of these drugs.

The study evaluated data from 248 men from MSK and institutions in Canada and the United Kingdom. The AR-V7 status was determined to analyze circulating tumor cells (CTCs) in a single blood draw. The men were followed for up to 4.3 years.

Men with AV-V7-positive CTCs lived longer when treated with chemotherapy (median overall survival was 14.3 months) compared with those treated with AR Inhibitors (7.3 months). In contrast, men with AR-V7-negative CTCs lived longer when treated with AR Inhibitors (median overall survival 19.8 months) than those treated with chemotherapy (12.8 months). 

“That is a significant difference in survival time and illustrates the value of this test in making a more informed treatment decision,” Dr. Scher says. “Even for AR-V7 patients who cannot receive chemotherapy — or choose not to — this test can help them avoid ineffective AR inhibitors and direct them to other treatments or enrollment in a clinical trial.”

Currently, the Oncotype DX® AR-V7 Nucleus Detect™ test is not covered by insurance.  Cancer ABCs has spoken with Genomic Health who has told us that the cost of the test is approximately $4,000.  They also told us that they have a generous program to help support people unable to afford the test.  If you are interested in financial assistance, send us an email, and we will arrange for you to speak with someone at Genomic Health.

Currently, Genomic Health is working hard to have Medicare cover the cost.  If they are successful, they will then tackle the other private insurance companies.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs. He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.