Large Prospective Trial Validates Detection of AR-V7 Biomarker Using Epic Sciences' Platform to Predict Treatment Outcomes for Patients with Advanced Prostate Cancer
SAN DIEGO, March 13, 2019 /PRNewswire/ -- Epic Sciences, Inc. (Epic) today announced the publication of results from a multicenter prospective trial validating the biomarker AR-V7 (androgen receptor splice variant-7) as a predictor of resistance to anti-androgen therapy in men with metastatic castration-resistant prostate cancer (mCRPC). Data from the PROPHECY trial, published in the Journal of Clinical Oncology, demonstrate that detection of AR-V7 in circulating tumor cells (CTCs) in blood is predictive of whether men with mCRPC have become resistant to androgen-receptor signaling (ARS) inhibitors and have a low chance of benefit from further ARS therapy.
Many men with mCRPC live longer when treated with the potent androgen receptor (AR) pathway inhibitors enzalutamide and abiraterone, which are considered the standard of care. However, in patients previously treated with one round of AR therapy, response rates are low and progression-free survival (PFS) and overall survival (OS) times are short. Moreover, cross resistance between these agents is common, and clinical features alone are unable to identify tumors that are cross-resistant. Therefore, predictive biomarkers are urgently needed to permit physicians and patients to select the most optimal therapies.
In the paper entitled "Prospective multicenter validation of AR-V7 and hormone therapy resistance in prostate cancer: the PROPHECY study," researchers led by Andrew J. Armstrong, M.D., ScM, FACP, Professor of Medicine, Surgery, Pharmacology and Cancer Biology; Director of Research, the Duke Cancer Institute Center for Prostate and Urologic Cancers, Divisions of Medical Oncology and Urology at Duke University, conducted this prospective, blinded clinical trial to validate the predictive significance of baseline CTC AR-V7 based on PFS as the primary endpoint, as well as OS, in 118 men with mCRPC undergoing ARS inhibitor therapy.
In the latest validation, the trial met its primary endpoint and the researchers concluded the detection of AR-V7 in CTCs by two blood-based assays, including the Epic Sciences CTC nuclear-specific AR-V7 protein assay, is independently associated with shorter PFS and OS in men with high-risk mCRPC taking either abiraterone or enzalutamide. Patients who tested AR-V7 positive had worse survival by all measures. For the Epic assay, the median PFS for AR-V7 positive versus AR-V7 negative patients was 3.1 versus 6.1 months, respectively. The median OS for AR-V7 positive versus AR-V7 negative patients was 8.4 versus 25.5 months, respectively. Additionally, no AR-V7 positive patients had a PSA or radiographic response to abiraterone or enzalutamide. The trial results indicate men with mCRPC who test positive for AR-V7 should be offered alternative, more effective treatments, such as taxane chemotherapy or a clinical trial of an investigational therapy.
The AR-V7-based test developed by Epic Sciences is now available to the estimated 50,000 men in the United States with advanced prostate cancer through Genomic Health's commercial launch of the Oncotype DX® AR-V7 Nucleus Detect™ test and is now covered by Medicare.
"In this study, we demonstrate in a prospective, blinded manner that men with high-risk metastatic castration-resistant prostate cancer who are AR-V7 positive have little evidence of clinical benefit from abiraterone or enzalutamide, with short duration of overall and progression-free survival. Epic Sciences' AR-V7 test may better inform the decision to pursue further ARS therapy prior to starting second line ARS treatment, rather than using these agents for a few months and then stopping if the treatment is ineffective," said Dr. Armstrong.
Dr. Armstrong continued, "One of the unique aspects of this multicenter study was that laboratory investigators were blinded to the clinical results, and clinicians were blinded to the laboratory results, and that the definitions of a positive test for AR-V7 were defined in advance and thus prospectively validated. Having a reliable test that is associated strongly with a lack of clinical benefits to a therapy can help a patient and doctor pick a more effective therapy and not waste valuable time, resources and unnecessary toxicities from an ineffective, cross-resistant drug. Such information can enable oncologists to identify potentially life-extending treatments for these men with aggressive disease."
Dr. Armstrong originally presented the top-line PROPHECY data in an oral presentation at the ASCO 2018 Annual Meeting.
"Demonstration in the PROPHECY trial of our AR-V7 test's ability to predict which patients will not respond to a frequently utilized and important drug class is a tremendous achievement," said Ryan Dittamore, Chief of Medical Innovation at Epic Sciences and co-author of the study. "This clinical evidence further supports the value of our liquid biopsy test in providing critical information for the clinical management of patients with advanced prostate cancer."
The results from a second blinded, multi-center clinical utility study of the Epic AR-V7 test were published in JAMA Oncology in September 2018.
The PROPHECY study was supported by a grant from the Prostate Cancer Foundation and Movember as well as infrastructure support from the Department of Defense Prostate Cancer Clinical Trials Consortium (DOD PCCTC).
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