A blood test that measures the spliced variant of an androgen receptor called AR-V7 in circulating tumor cells successfully predicted resistance to commonly used hormonal therapy agents in advanced prostate cancer, a validation study confirmed.
In the multicenter PROPHECY trial, researchers found that the use of two blood-based assays for measuring AR-V7 -- the Johns Hopkins modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear AR-V7 protein assay -- demonstrated that AR-V7 positivity is associated with resistance to the androgen receptor (AR) pathway inhibitors abiraterone and enzalutamide.
"We confirmed that AR-V7, if positive, was associated with a lack of benefit with these therapies – a very low probability of a response to these hormone drugs, a short time to progression, and very low survival for men who test positive," Andrew Armstrong, MD, Duke Cancer Institute, told MedPage Today.
Armstrong, who led the study, said the AR-V7 test allows physicians to make more informed recommendations about alternative therapies to patients who test positive. "And those alternatives might include therapies already available, including docetaxel chemotherapy," said Armstrong. "Or physicians may want to enroll patients in clinical trials of some new agents that might have more promise than using a drug that's not likely to work."
Results of the study were published in the Journal of Clinical Oncology.
Androgen receptor (AR) pathway inhibitors abiraterone and enzalutamide have become the standard of care for men with high-risk metastatic castration-resistant prostate cancer. However, as Armstrong and colleagues pointed out, resistance to these therapies develops in men who have been previously treated with these agents, leading to lower response rates and shorter progression-free and overall survival times.
"And there is a lot of cross-resistance between these therapies, meaning that when one of the drugs stops working, the other drug often won't work very well," Armstrong said, adding that it is very difficult to predict when cross resistance will occur.
Earlier studies, including from Johns Hopkins University and Memorial Sloan Kettering Cancer Center, suggested that AR-V7 can be detected in circulating tumor cells and predict resistance. PROPHECY was designed to validate those findings.
Armstrong and colleagues enrolled 118 patients with high-risk metastatic castration-resistant prostate cancer. Of these patients, 58 were starting treatment with enzalutamide, 55 with abiraterone, and five were receiving both concurrently.
Median progression-free survival (PFS) was 5.8 months (95% CI 4.1-7.6 months), and median overall survival was 20.3 months (95% CI 17.0-27.2 months) for the overall cohort, which, Armstrong and his colleagues noted, reflected "the high risk features of this population."
In the overall study cohort, approximately 10%-24% of men were AR-V7 positive, depending on which of the assays were used. For both PFS and OS, there were significant differences between AR-V7 positive and AR-V7 negative men for both assays.
For the Johns Hopkins AR-V7 assay, the median PFS for AR-V7–positive versus AR-V7– negative patients was 3.1 vs 6.9 months, respectively (HR, 2.4; 95% CI 1.5-3.7). For the Epic AR-V7 protein assay, the median PFS for AR-V7–positive versus AR-V7–negative patients was 3.1 vs 6.1 months, respectively (HR, 2.5; 95% CI 1.3-4.7).
Median overall survival for AR-V7– positive versus AR-V7–negative patients was 10.8 vs 27.2 months, respectively (HR, 3.9; 95% CI 2.2-6.9), for the Johns Hopkins assay, while the median overall survival for AR-V7– positive versus AR-V7–negative patients was 8.4 vs 25.5 months, respectively (HR, 3.4; 95% CI 1.6-7.0), for the Epic assay.
AR-V7 detection by both the Johns Hopkins and Epic assays was independently associated with shorter PFS (HR 1.9, 95% CI 1.1-3.3; and HR 2.4, 95% CI 1.1-5.1), respectively. The same was true for overall survival (HR 4.2, 95% CI 2.1-8.5; and HR 3.5, 95% CI 1.6-8.1), for the Hopkins and Epic assays, respectively.
Armstrong noted that the Epic AR-V7 test is now covered by Medicare. "Because of this, and other studies, it has become a clinically useful test for some men," Armstrong said. "It can be ordered by physicians nationwide, and the results come back reasonably quickly -- within a week."
However, "there are some caveats," Armstrong told MedPage Today. "It's not a perfect test for resistance. There are other mechanisms of resistance to these drugs and this only measures one aspect of this resistance. What I really like about the PROPHECY study, which is part of ongoing work, is that we are trying to discover those other mechanisms of resistance beyond AR-V7."
See article for authors' disclosures of potential conflicts of interest
Scientists discover hormone therapys impact on prostate
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai. We were able to demonstrate that we can accurately predict whether or not resistance against abiraterone or enzalutamide is present in a patient, Cristof Winter, MD, PhD, physician and bioinformatician at TUM Institute of Clinical Chemistry and Pathobiochemistry, herex27s What to Know About Flu Season Right Now said in the release. Each year, according to the. No patient with high AR-V7 levels achieved PSA response, compared with 50 of men with low AR-V7 levels (. Heck and colleagues developed a practical and robust what the Number of Pushups You Can Do Says About Your Heart liquid profiling approach for direct, absolute quantification of AR-V7 and androgen receptor full-length mRNA levels in peripheral whole blood without the need for circulating tumor cells to predict resistance to abiraterone and enzalutamide. Their findings also point to a simple blood test that may help doctors predict when this type of hormone therapy resistance will occur. Treatment for...
Hormone therapy, which blocks the production of these hormones (androgens or their ability to bind to specific androgen receptors, is often used to lower the risk of an early prostate cancer coming back after treatment, and to shrink advanced prostate tumors. Nevertheless, the optimal method for determining AR-V7 status has yet to be determined, the researchers wrote. Thöne, PhD, from TUM Institute of Clinical Chemistry and Pathobiochemistry, said in the release. Overall, 41 of patients achieved PSA response. Seitz and colleagues investigated an approach to determine the presence of AR-V7 in peripheral whole blood and its association with treatment-specific outcomes for patients with castration-resistant prostate cancer treated with abiraterone or enzalutamide.