Treatment of Advanced Prostate Cancer: Expert Evaluations of Recent Studies - Episode 1

Use of AR-V7 as a Prostate Cancer Biomarker


Raoul S. Concepcion, MD, FACS: Hello and thank you for joining this OncLive TV Peer Exchange which features expert insight on advanced prostate cancer. My name is Raoul Concepcion and I am the Editor-in-Chief for Urologists in Cancer Care and the Director of Advanced Therapeutics at Urology Associates in Nashville, Tennessee. Recent and emerging data are providing signals as to the benefit of early treatment in patients who have high-grade prostate cancer.

In this panel discussion, my colleagues and I will be discussing the results of several studies that address questions related to treatment of patients with or without frank metastatic disease. We’ll also discuss mechanisms of resistance to therapy and the potential impact of early treatment or sequencing of therapies.

I’m joined today by: Dr. Mike Fabrizio of Urology of Virginia. Mike is a Professor of Urology and Director of the Endo-Urology Fellowship at Eastern Virginia Medical School. I’m also joined by Dr. Jorge Garcia who is the Director of the Advanced Prostate Cancer Research program at the Taussig Cancer Institute and Glickman Urologic & Kidney Institute in Cleveland, Ohio; Dr. Judd Moul is the James H. Semans Professor of Surgery and Director of the Duke Prostate Center, Division of Urologic Surgery at Duke University Medical Center; and Dr. Charles Ryan who is Professor of Clinical Medicine and Program Leader of Genitourinary Medical Oncology at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, California.

Thank you again for joining us today. Let’s discuss recent findings as presented surrounding the androgen receptor (AR-V7) splice variant and response to taxanes in men with metastatic castration resistant prostate cancer.

Jorge A. Garcia, MD, FACP: The initial data presented and published in the New England Journal of Medicine by Emmanuel Antonarakis aimed to assess whether or not men with metastatic castration-resistant prostate cancer who harbor a specific mutation in AR (specifically with splice variant 7) would predict for response to oral therapy with enzalutamide and/or abiraterone acetate.

In their data, 62 patients were initially tested for this specific splice variant and then patients went on to receive either enzalutamide and/or abiraterone acetate. Findings of that data demonstrate that patients who harbor that specific mutation in the ligand binding domain had no clinical benefit to either oral agent. More importantly than that, we’re looking for biomarker development in prostate cancer.

One of the challenges of these data is how we detect that it’s splice variant. The initial data looked at circulating tumor cells, which is a controversial way of assessing men in terms of a biomarker for castration-resistant disease. Nonetheless, I think those data are powerful enough to demonstrate no benefit from oral therapy if you have a splice variant 7.

More important is whether or not that splice variant could protect subsequent response to a taxane-based therapy, and that’s what Emmanuel presented at ASCO GU this year. In his small sample size, approximately 30 patients went on to receive cabazitaxel-based chemotherapy. Having the presence of that splice variant did not predict for subsequent benefit or lack thereof to cabazitaxel. Therefore, I don’t think having that splice variant should be utilized to define who needs chemotherapy in this context.

Raoul S. Concepcion, MD, FACS: I think it’s important for the audience to understand that this CTC assay looking for the mRNA and the splice variant is not commercially available. From your perspective, what are the limitations of this right now? What does the audience need to take home about splice variants measurements, biomarkers, etcetera?

Charles J. Ryan, MD: That’s the challenge. It’s a very exciting story because it’s a predictive biomarker and heretofore, we have not had that in prostate cancer at all. So, assuming that it is validated and that it becomes a commercially available test, it would be useful because it will prevent us from using an expensive therapy.

It will prevent us from wasting patients’ time, but you highlight the very issues that remain unanswered, which is when is this test going to be available. How reproducible is it going to be? And keep in mind that a large proportion of patients with CRPC don’t have circulating tumor cells. And, in fact, it could mean that the very patients in whom we want to begin treatment with enzalutamide or abiraterone are those who would harbor a very low burden or zero circulating tumor cells.

So, even if this becomes commercially available tomorrow, there are still going to be questions that remain about it. My understanding is that the original data came from an assay that was developed in Johns Hopkins and they deserve a large amount of credit for developing that assay. There’s a company that’s developing a commercial assay as well, and those have been done in parallel. But, for the practicing physician out there right now, it remains something they should know about but it’s not something they can act on.

Transcript Edited for Clarity