SAN DIEGO—California-based cancer diagnostic development company Epic Sciences Inc. announced in June two promising new sets of data evaluating their assays for the nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells as a predictive biomarker for metastatic castration-resistant prostate cancer (mCRPC).
The first of these data sets was presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting from June 1 to 5 in Chicago. The company and its collaborators presented a total of five studies, including an oral abstract of a study conducted in partnership with the Duke Cancer Institute titled “The PROPHECY trial: Multicenter prospective trial of circulating tumor cell (CTC) AR-V7 detection in men with mCRPC receiving abiraterone (A) or enzalutamide (E).”
According to Ryan Dittamore, chief of medical innovation at Epic Sciences, the studies demonstrate the further validation and clinical utility of their nuclear-localized AR-V7 test, as well as other liquid biopsy tests under development.
Following this announcement, a second study published June 28 in JAMA Oncology validated the predictive value of a liquid biopsy test and demonstrated a survival benefit for patients. The results chronicled an independent, multicenter, blinded study conducted by an international team of researchers from Memorial Sloan Kettering Cancer Center (MSK), Epic Sciences, the Institute of Cancer Research and London Health Sciences Centre collected over four years. The study followed 142 mCRPC patients treated at either MSK, The Royal Marsden or the London Health Sciences Centre, and concluded that nuclear-localized AR-V7 protein in circulating tumor cells can identify patients who may live longer with taxane chemotherapy versus androgen receptor signaling inhibitor (ARSi) treatment.
“This liquid biopsy test addresses a critical unmet need at a decision point in management to predict and select the therapy that is most likely to extend a patient’s life,” said Dr. Howard Scher, who led the study, in a media statement. Scher is the co-chair for the Center for Mechanism Based Therapy and the head of the Biomarker Development Initiative at MSK. “During the treatment of metastatic prostate cancer, physicians will now be able to use AR-V7 status to determine when a patient’s cancer has become resistant to androgen receptor-directed therapy and will respond better to chemotherapy, enabling the patient to live longer.”
The blood test, called Oncotype DX AR-V7 Nucleus Detect, is commercially available in the United States through Epic Science’s partnership with Genomic Health Inc.
“The PROPHECY data focused on validating AR-V7 as a negative predictive biomarker for use of abiraterone or enzalutamide,” says Dittamore. “Given that every patient who was positive for nuclear-localized AR-V7 in our test has no patient benefit, the natural question is: ‘Will these patients live longer on chemotherapy?’ The Scher et al. publication validates this—that patients who test positive with the Oncotype DX AR-V7 Nucleus Detect test will live longer on chemotherapy than when treated with ARSi inhibitors, abiraterone or enzalutamide. Given the two datasets, the test has been validated in the context of the clinical question being asked.”
The results address an important unmet need for physicians and patients faced with a choice about how to approach treatment of metastatic castration-resistant prostate cancer.
“Prior to AR-V7, physician intuition was the primary decision-making strategy in determining a therapeutic sequencing for patients with mCRPC,” Dittamore explains. “Validating nuclear-localized AR-V7 protein as a predictive test in this decision demonstrates a survival advantage of AR-V7 over physician intuition. The data support that the use of Oncotype DX AR-V7 Nucleus Detect test has the ability to increase patient survival through better decision making.”
A specific, predictive biomarker for prostate cancer has been difficult to isolate, with the male equivalent of the breast cancer biomarker HER-2 proving to be elusive. Dittamore credits his team’s success on their approach to the challenge.
“Our approach was to lead not with the biomarker, but with an important unmet, relevant clinical question,” he tells DDNews. “The clinical question and test performance requirements dictated the biomarker, rather than the other way around. During our journey with MSK, we ended up looking at 20 different biomarkers before we landed on nuclear-localized AR-V7 protein. After initial feasibility with AR-V7, we locked down the assay and tested in multiple cohorts to validate the test.”
The Oncotype DX AR-V7 Nucleus Detect test was designed by Epic Sciences and based on results from multiple studies led by MSK. It is the first and only liquid biopsy test of its kind designed to prolong the lives of men with metastatic castration-resistant prostate cancer by helping their physician identify the most effective treatment. The test detects the AR-V7 protein in the nucleus of circulating tumor cells through a blood draw utilizing Epic Sciences' No Cell Left Behind platform to identify patients who are resistant to androgen-receptor-targeted therapies, and who should instead switch to chemotherapy. The Oncotype DX AR-V7 Nucleus Detect testing is performed by Epic Sciences at its CLIA-certified laboratory in San Diego.