AR-V7 is a promising biomarker that needs to be validated in appropriately designed trials.
—Howard Scher, MD
AR-V7 is only one of the many prostate cancer predictive biomarker candidates currently under investigation,” said Howard Scher, MD, Chief of the Genitourinary Service at Memorial Sloan Kettering Cancer Center in New York. While preliminary data are promising, further development of AR-V7 will first require ensuring that the assay is analytically valid—one that is reliable and reproducible across different laboratories—to measure it, followed by a sequence of trials designed to generate evidence supporting its use within a specific clinical context.
Dr. Scher noted that different assays may be used to measure discrete aspects of the same biomarker. Dr. Antonarakis’ group looked for a splice abnormality in the mRNA of the androgen receptor in the blood.
Potential to Improve Decision-Making
As drugs are approved for indications, biomarkers are approved for the specific way in which they improve decision-making—their context of use, Dr. Scher continued. For example, a biomarker predicting response to therapy could be useful in a patient who has had disease progression on one form of therapy, in need of the decision on what to do next.
“Predictive biomarkers help guide treatment selection throughout the course of illness,” he stated. “In men experiencing initial hormone resistance, it is important to identify those who are unlikely to respond to hormonal agents such as enzalutamide and abiraterone for whom chemotherapy may be more effective. Similarly, as the disease progresses further and response rates to enzalutamide or abiraterone are lower, the goal is to identify the minority of patients still likely to respond to these agents, while offering alternative treatment to those who are not. The results presented by Dr. Antonarakis suggest that the presence of the AR-V7 predicts for nonresponse to enzalutamide (Xtandi) and abiraterone (Zytiga), and response to a taxane. ”
“Early data on AR-V7 is encouraging and warrants further development. A coordinated effort to establish analytically valid AR-V7 assays, and to prospectively evaluate the presence of the variant and clinical outcomes in dedicated trials is already underway,” he stated. ■
Disclosure: Dr. Scher reported no potential conflicts of interest.
The search is on in prostate cancer to identify predictive and prognostic biologic and genomic markers that go beyond traditional ones. Several groups are working in this area. One marker that has received much attention is a splice abnormality in the androgen receptor (AR) called AR-V7.