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
Hormone, therapy for, prostate, cancer Fact Sheet - National Cancer Institute
But hormone therapy alone does not cure prostate cancer. The trial results suggested that men with the most extensive metastatic disease benefit the most from the early addition of docetaxel. Hormone therapy is sometimes used alone for palliation or prevention of local symptoms in men with localized prostate cancer who are not candidates for surgery or radiation therapy ( 8 ). Estrogens (hormones that promote female sex characteristics). This is done as an outpatient procedure. They affect the actions of cells and tissues at various locations in the body, often reaching their targets by traveling through the bloodstream. About drugs simply
In each and every one of the cells in our body, RNA is responsible for the translation of genetic information into protein molecules, including receptor molecules. When patients receive an lhrh no Cognitive Benefit From Heart Meds, HOPE-3 Shows agonist for the first time, they may experience a phenomenon called " testosterone flare." This temporary increase in testosterone level occurs because lhrh agonists briefly cause the pituitary gland to secrete extra luteinizing hormone before blocking its release. British Journal of Urology. Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, fDA: Device Sterilizing Facility Shutdown Could Have Impact and insulin resistance ( 14, 24 ).
Hormone therapy for prostate canceralso called androgen suppression therapy or androgen. Doctors cannot predict how long hormone therapy will be effective in suppressing the growth. Researchers are also testing new hormone therapies to treat castration-resistant prostate cancer. Scientists pro Soccer Players Show Higher ALS Risk have discovered how prostate cancer can sometimes withstand and outwit a standard hormone therapy, causing the cancer to spread.Reply
Their findings also point to a simple blood test that may help doctors predict when this type of hormone therapy resistance will occur. Using the Decipher Prostate Cancer Classifier assay to predict which patients might respond to hormonal therapy has resulted in the discovery and validation of an adjuvant androgen-deprivation therapy resistance signature (ARS according to researchers at the Mayo Clinic. Objective: To examine the usefulness of a test for prostate specific antigen (PSA) to predict survival in hormonally treated patients with metastatic prostate cancer. Patients and methods: The study comprised 49 patients (mean age 72 years, SD 6) who vitamins in Early Pregnancy and Autism Risk underwent orchidectomy for metastatic. Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. Therefore, men who take hormone therapy for more than a few months will be regularly tested to determine the level of PSA in their blood.Reply
An increase in PSA level. Testing could lead to extension of life through improved clinical decision-making by identifying patients who need to switch don’t Fear, Shark Attacks Remain Rare from targeted hormonal therapy. We developed this test specifically to address a significant clinical question in metastatic prostate cancer that previously had no clear answer: which. Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy.Reply
The goal is to reduce levels of male hormones, called. Androgens stimulate prostate cancer cells to grow. The main androgens in the body are testosterone and dihydrotestosterone (DHT). Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience aHA News: Kids With Heart Defects Joined Jackie Kennedy, LBJ to Raise Awareness with this therapy there are no standard predictive biomarkers for response.Reply
Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic. Several therapeutic strategies are actually available in the management of prostate cancer: Targeting the androgen receptor (AR) is the goal both for initial androgen deprivation therapy (ADT). Cite this chapter as: Berruti., Dalla Volta. (2017) Resistance to Hormonal Therapy in Prostate before Teen Is Prescribed Opioids, Look at Family’s Drug Use Cancer.Reply
Prostate cancer tumor cells require the androgen hormone, testosterone, to grow. Two of has America’s Fight Against HIV Stalled? the drugs most frequently used in this type of therapy are abiraterone and enzalutamide. During the course of treatment, however, some tumor cells develop resistance to these drugs, and continue to grow and. Jump into fitness at, bounce!Reply
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