Enzalutamide (Xtandi®) and abiraterone acetate (Zytiga®) are two approved hormone therapies commonly prescribed for men with hormone-resistant advanced prostate cancer. They block the androgen receptor signaling that is essential to the cancer’s growth. Although they represent breakthroughs in metastatic treatment, 20 to 40 percent of patients fail to respond to them. These men with advanced prostate cancer have an abnormal version of a prostate cancer protein that binds with testosterone. The protein is missing a key connector that binds to abiraterone and enzalutamide. The abnormal protein is caused by a genetic variant called AR-V7. Johns Hopkins researchers discovered that the variation, which lacks a portion of the full androgen receptor, was associated with resistance to abiraterone and enzalutamide. The drugs failed to block androgen receptor signaling, thus allowing prostate cancer cells to keep growing. Most patients who test positive for AR-V7 get limited or no benefit from abiraterone or enzalutamide. Conversely, Johns Hopkins researchers discovered that prostate cancer patients who lacked the AR-V7 androgen receptor variation survive longer than those with the variation. The initial study, “AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer” was published in the New England Journal of Medicine in 2014. A test for the genetic variant, AR-V7 was described further in this website’s October 13th, 2015 post.
An article in the April 24th, Prostate Cancer News Today, stated that Qiagen will begin marketing the test that Johns Hopkins University developed. If doctors know that a prostate cancer patient is resistant to the drugs, they can develop a more tailored treatment. The test, called AdnaTest Prostate Cancer Panel AR-V7, will detect that resistance. The test is called a liquid biopsy because it examines circulating tumor cells (CTC’s) in blood instead of tissue. It shows whether cancer cells in a blood sample have the AR-V7 variation.
In addition to the test being used in treatment, researchers can use it to help select patients for clinical trials. In a recent study, thirty-one men received Zytiga and 31 Xtandi. The results were clear. The PSA response rate was zero in patients with the AR-V7 variant. In other words, none of the patients with the variant responded to the drugs. In contrast, 54% of patients who lacked the variant responded to Zytiga, and 68% to Xtandi. Overall survival rates of patients with the variant were 5.5 months with Zytiga and 10.6 months with Xtandi. Patients without the variation survived beyond the duration of the study.
QIAGEN is working with several pharmaceutical companies on trying the test in prostate cancer clinical trials. They plan to make the AdnaTest kit commercially available this year.