AR-V7: From Concept to Clinic
Updated: Apr 4, 2020
01 July 2018
It’s been a long time coming, but I can now publicly share some very good news: our second validation study of the AR-V7 biomarker in circulating tumor cells (nuclear-localized protein) has been accepted to JAMA Oncology and is available online. But really, the publication alone is merely one act of a story that has been a big part of my life the last few years. I’ll do my best to condense the story:
Act 1: A few years ago, my team (collectively, Epic Sciences; we are a small, close-knit company) designed a diagnostic test to detect a specific type of protein (AR-V7, or splice variant 7 of the androgen receptor) in the circulating tumor cells in the blood of men with metastatic prostate cancer. The existing biology suggested that the presence of this protein variant in circulating tumor cells might identify men for whom next-generation anti-hormonal therapy might not work, and for whom might actually benefit more from standard chemotherapy (these are the two most common options for men with metastatic prostate cancer). The benefit of a circulating tumor cell-based diagnostic test for metastatic prostate cancer patients is that it involves a standard blood draw; the next best method for most patients is a bone biopsy, which is far from an innocuous procedure. A lot of much more talented lab scientists carefully engineered the test; I mostly deal with numbers and clinical biostatistics.
Act 2: We tested the blood of close to 200 metastatic prostate cancer patient samples taken immediately before they started a new therapy. Our collaborators at Memorial Sloan-Kettering followed their outcomes to see if the underlying biology and technology held up on a human scale. We found that patients testing positive had poor initial response to the hormonal agents, and some having definitive benefit from chemotherapy. We also found that, beyond the initial response, these patients actually lived longer! The biomarker-treatment interaction had a significant relationship with the patients’ long-term survival. These results were published in the journal JAMA Oncology
Act 3: We tested another 142 patients’ blood with the AR-V7 test and followed their outcomes, similarly to before. We sought to determine if the technology and biology was robust enough to see the overall survival effect again. When we un-blinded the results, it became immediately clear that it had hit the mark. I’ve been wanting to tell the world for some time, and now I can. These results were released online this week, again in the journal JAMA Oncology. I was involved with study planning and design, as well as biostatistical analyses with our collaborators at Memorial Sloan-Kettering.
Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer
Act 4: A team of physician-scientists at multiple institutions across the U.S. conducted a study (the PROPHECY trial) to independently test the association of the positive test result with poor outcome on the standard of care anti-hormonal agents. The initial results of the study were presented at the annual American Society of Clinical Oncology meeting in Chicago earlier this month, and were very consistent with results observed in our two previous publications. We had no role in design or analysis of this study, and it’s nice to see these consistent results. Some press coverage of the results in Urology Today.
Act 5: Simply making a diagnostic test is not good enough; it must be able to get in the hands of patients and physicians who need it. We have a collaborative agreement with Genomic Health to distribute the test and provide sales and medical affairs support to oncology and urology offices across the U.S. (link to Commercial Page): Also, a diagnostic test like this would be little use if it was not covered by insurance. While discussions with private insurance bodies are ongoing, we did receive a favorable draft LCD from CMS (who oversees Medicare, the V.A., etc) which means that it might soon be covered by public insurance programs.
In closing, it’s been a wild journey so far, the type that provides the “good” stress to expand and grow professionally. But, many milestones and a lot of work remains. AR-V7 is just the first diagnostic test that we’ve developed commercially with our technology. I cannot share too much along these lines at the time being, but I can share that we are actively pursuing other uses of the technology, within prostate cancer and beyond, and I look forward to the hard work and unique challenges ahead.
I’d like to thank you for visiting, dear reader. Until next time!