Study from MSK and Epic Sciences shows only nuclear-localized AR-V7 Is predictive of therapy benefit for patients with metastatic prostate cancer.

Results published in European Urology represent breakthrough in applying liquid biopsy to guide treatment decisions in prostate cancer.

Investigators from Memorial Sloan Kettering Cancer Center (MSK) and Epic Sciences published findings in European Urology, that only nuclear localization of AR-V7 protein in circulating tumor cells (CTCs) from metastatic castration resistant prostate cancer (mCRPC) patient blood samples is predictive of therapeutic benefit. Previous work by the same team, reported in JAMA Oncology, demonstrated that nuclear localized AR-V7 protein in CTCs was predictive of a 76 percent reduction of risk of death for mCRPC patients who received taxane chemotherapy versus Androgen Receptor Signaling inhibitors (ARSi), Zytiga and Xtandi.

The publication describes the comparison of clinical utility of detecting any AR-V7 protein in CTCs versus the previously described nuclear AR-V7 scoring criteria. The study analyzed 191 mCRPC patient samples and found that patients with a less restrictive scoring criteria utilizing any AR-V7 expression detected in CTCs exhibited generally poor outcomes on ARSi, Zytiga and Xtandi. However, approximately 13 percent of the positive patients still responded to ARSi.

In contrast, none of the patients with nuclear localized AR-V7 protein expression in CTCs exhibited a response to ARSi, demonstrating superior performance of the nuclear localized approach. The difference between the scoring criteria also made significant differences in the prediction of therapeutic benefit of switching from commonly utilized ARSi to taxane chemotherapy, with only the nuclear scoring criteria demonstrating extension of life through switching therapies.

“The study results highlight the importance of robust analytic and clinical validation of predictive cancer biomarker tests at key clinical decision points in patient management,” said Howard Scher, MD, chief of the genitourinary oncology service at MSK and lead author of the study. “The decision to prescribe intravenous treatment with a taxane over an oral ARSI needs to be based on a thoroughly evaluated technology in order to ensure patient outcomes are improved. Our work demonstrates the importance of the rigorous validation of the AR-V7 assay to guide the choice of systemic therapy in patients with metastatic disease.”

The AR-V7 biomarker has been tested in multiple studies in CTCs and whole blood through detection of both AR-V7 protein and mRNA. While AR-V7 mRNA studies have demonstrated worse outcomes to ARSi, therapeutic responses to ARSi have been reported in AR-V7 mRNA positive patients.

“We know that when AR-V7 protein is detected in the nucleus of the tumor cell, those patients demonstrate high specificity to ARSi resistance,” said Ryan Dittamore, vice president of translational research & clinical affairs, Epic Sciences and co-author on the study. “This study shows that using Epic Sciences’ proprietary CTC platform to determine whether AR-V7 protein is sequestered in the cytoplasm or translocated to the nucleus can provide an important clinical difference compared to other technologies with less specific AR-V7 detection techniques.”

In 2016, Epic Sciences partnered with Genomic Health, Inc., to offer the highly-specific nuclear AR-V7 liquid biopsy test later this year. Provided through Genomic Health’s world-class Oncotype IQ Genomic Intelligence Platform and performed at the Epic Sciences CAP/CLIA-certified laboratory, the test is poised to address the needs of about 50,000 patients each year in the United States alone.

About Epic Sciences

At Epic Sciences, we develop clinically proven predictive tests to detect and monitor cancer at the individual cell level. With a proprietary rare-cell detection engine, we provide insights to clinical, biotech, pharmaceutical and academic teams on how cancer emerges, mutates and remits so they can make pivotal decisions at every point in patient treatment with greater certainty. Recognizing the unique nature of each person’s cancer, we offer truly personalized diagnostic tests, while being non-invasive for the patient.

We have developed the first clinically proven predictive test for metastatic castration-resistant prostrate cancer (mCRPC), the Epic AR-V7 test. Using the same rare-cell detection platform and Epic’s biobank of over 30,000 blood samples, each profiled with predictive biomarkers, we partner with leading pharmaceutical and biotechnology companies, major cancer centers, the National Cancer Institute (NCI), and the National Institutes of Health (NIH) to pursue additional predictive tests for breast, ovarian, colon and other cancers and diseases. Our mission is to revolutionize cancer care and therapies to make them as precise, safe and life-sustaining as humanly possible.

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