Genetic Test Can Determine Whether Expensive Treatments Will Work in Metastatic Cancer

Enzalutamide and abiraterone are drugs that are used to treat metastatic prostate cancer that is growing despite hormonal therapy.  The two drugs work differently.  Enzalutamide targets the androgen (e.g. testosterone) receptor on a cell while abiraterone inhibits androgen synthesis.   The treatments can cost as much as $100,000 per year and not every man responds to either drug.  Resistance to both of these drugs has been observed.  Up till now, there was no way to determine whether either drug would work in a given case except to prescribe one and see if it worked, and if it didn’t, then try the other.  Recently however, researchers at Johns Hopkins in Baltimore have found that a particular genetic androgen receptor variant on prostate cancer cells, called AR-V7, is associated with resistance to these drugs and they have developed an assay to look for AR-V7 in prostate cancer cells circulating in the blood.  Their study was published in September 2014 in the New England Journal of Medicine.  In their initial studies, 39% of 31 men taking enzalutamide and 19% of men taking abiraterone had detectable AR-V7 in the prostate cancer cells circulating in their bloodstream.  Of the men on enzalutamide, those who were AR-V7 positive had poorer PSA response rates and shorter progression-free survival compared to men with no detectable AR-V7.  A similar situation was observed for men taking abiraterone.  After adjusting for other factors, the researchers concluded that men who were AR-V7 positive had “independently inferior responses to the two drugs” than men whose blood showed no AR-V7.  During the study, it was also observed that some men who had been AR-V7 negative before treatment changed during the course of therapy and became AR-V7 positive.  These men had intermediate clinical outcomes.  The AR-V7 variant was found to be relatively common among men with hormone-resistant prostate cancer.  It was present in 12% of the men who had received neither drug but it appeared in 67% of the men after exposure to both enzalutamide and abiraterone.  Larger studies are underway to determine if AR-V7 can eventually be used as a biomarker to predict primary or acquired resistance to androgen pathway-targeted therapies.  The turn-around time for an AR-V7 assay is only three days, hence the test could be used in the near future for men contemplating treatment with either of the two drugs.  If they test positive for AR-V7, these men could potentially be steered to alternative treatments such as immunotherapy, chemotherapy or radiotherapy.