Download Personalizing Advanced Prostate Cancer Treatment

Personalizing Advanced Prostate Cancer
Treatment
Recorded on March 12, 2015
Emmanuel Antonarakis, MD
Assistant Professor, Oncology
Johns Hopkins School of Medicine
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Andrew Schorr:
Hello and welcome to Patient Power. I'm Andrew Schorr. At the 2015 ASCO GU meeting, doctors and researchers from
around the world gathered to discuss the latest in the treatment of prostate cancer, among them, Dr. Emmanuel
Antonarakis from Johns Hopkins University in Baltimore. He joins us once again on Patient Power to discuss his research
for a blood biomarker to help decide which men could benefit from chemotherapy.
Dr. Antonarakis, welcome back to Patient Power. Help us understand the significance of your research and what it means
for men with advanced prostate cancer.
Dr. Antonarakis:
Yes, thank you very much. So we're actually very excited about this research, because we think it's actually very applicable
to patients and to clinical practice. So about six months ago, we presented this first story about the AR-V7 biomarker. This
is a biomarker which we have developed at Johns Hopkins. Other groups are also working on it, and it's a blood-based test,
and we look for this mutation in the androgen receptor called AR-V7.
And what we showed in our previous work was if this mutation was present in circulating tumor cells from the blood of
patients, they did not have any response whatsoever to enzalutamide (Xtandi®) and abiraterone (Zytiga®), which are two
of the more novel hormone therapies for advanced prostate cancer.
So that was interesting and yet a bit discouraging, so the question was now we have a biomarker that we think we have
associated with resistance to abiraterone and enzalutamide, but what do those patients respond to? So the obvious
question was to examine the effect of chemotherapy.
So there are two chemotherapies which are approved for advanced prostate cancer, as you know, docetaxel (Taxotere®)
and cabazitaxel (Jevtana®). They are both called taxane chemotherapies, and they're related to each other. And what we
decided to do was to prospectively test the AR-V7 biomarker to see whether it was linked with resistance or response to
the taxane chemotherapy drugs.
And we investigated 37 patients, all of whom had a CTC, circulating tumor cell, blood test at baseline during the course of
therapy with the taxane and then at the time that the taxane was discontinued. And what we found to our surprise was
that patients who had the AR-V7 mutation present still could respond to the chemotherapy. Patients that did not have the
mutation also responded and perhaps at a slightly higher rate. Nevertheless, those patients that did have the AR-V7
present did have a 40 percent chance of responding to docetaxel or cabazitaxel.
So we were very encouraged by these results, because now we have a biomarker where if the biomarker is present, if
AR-V7 is positive, we have good evidence that those patients will not have any appreciable benefit from abiraterone or
enzalutamide. But they do, in fact, have quite a good chance of responding to taxane chemotherapy.
So this might, in fact, be what we call a treatment selection marker, in other words, a biomarker that can help us select
patients for one particular therapy over another. So in this case if the biomarker is positive, if the AR-V7 is present in the
circulating tumor cells, we might be able to direct that patient away from abiraterone and enzalutamide and towards the
chemotherapy drugs.
Andrew Schorr:
So with the number of nonchemotherapy treatments for advanced prostate cancer, does chemotherapy still fit in and for
which patients?
Dr. Antonarakis:
So I very much believe that there is a role for chemotherapy in the advanced prostate cancer patients, and I think
chemotherapy can be used in two situations. We now know that chemotherapy benefits patients with hormone-sensitive
metastatic prostate cancer. This was the data presented by Christopher Sweeney from the CHAARTED study. This made
a big splash at the national ASCO meeting last year in June, and what Dr. Sweeney presented [were] the results of the
CHAARTED study.
So this was a trial where patients with newly diagnosed metastatic prostate cancer who had never received hormone
therapy, the so-called hormone naive patients, were randomized to receive either standard hormone therapy alone,
androgen deprivation, or hormone therapy plus six doses of docetaxel chemotherapy given once every three weeks.
And the very surprising result was the patients that received the combination of chemo and hormone therapy had an
overall survival that was much, much longer than those patients that received the hormone therapy alone. So this is one
setting in which the use of chemotherapy combined with hormone therapy up front in patients with newly diagnosed
hormone-sensitive metastatic prostate cancer appears to have a huge benefit in terms of survival.
The patients that seemed to benefit the most from that study [were] those who had what was called extensive metastases.
Extensive metastases was defined as a patient that had more than four bone metastases or a patient that had a metastasis
in the liver or the lungs.
Now, in practice we may not adhere to that exact definition. So if I have the sense that a patient has extensive metastatic
disease and they may or may not meet that exact definition, I might still offer that patient a chemotherapy combined with
hormone therapy for the newly diagnosed hormone-sensitive cases.
The second scenario is for the man who has hormone-resistant prostate cancer, also called castration-resistant prostate
cancer, and this is where most of my research here at Johns Hopkins has focused on. And I think with the information from
the AR-V7 study we now might be able to more accurately define which patients might be best suited for chemotherapy in
the castration-resistant setting.
So if a patient with metastatic castration-resistant prostate cancer has the presence of the AR-V7 mutation in their
circulating tumor cells, that patient would probably have a better chance of responding to chemotherapy compared to
abiraterone or enzalutamide.
Now, that's a—that's a pretty big move for a patient because the chemotherapy is intravenous, it does certainly have more
side effects. And yet you wouldn't want to expose that patient to an oral therapy that was not going to work just because it
happened to be a pill and just because it happened to be less toxic. So in my opinion, the AR-V7 biomarker could be one
potential biomarker that could select patients that would benefit most from chemotherapy in the castration-resistant
prostate cancer setting.
I must stress at this point in time the AR-V7 test is not available or offered outside of Johns Hopkins, and it is not currently
commercially available through a biomarker company. So at this point in time, the only way that a patient can get tested is
by participating in a research study either here at Johns Hopkins or a small number of additional institutions who are also
testing the AR-V7 biomarker.
Andrew Schorr:
Based on your study results, doctor, what questions should a man with advanced prostate cancer be asking their doctor
today, so they make sure they get the treatment that's right for them?
Dr. Antonarakis:
So my sincere hope is that in the next one to two years the AR-V7 biomarker test will be commercially available and
offered to patients throughout the country and hopefully throughout the world. And until that time comes, I think what
patients should ask their physicians is can I be referred to a center that is performing AR-V7 testing?
As I mentioned, Johns Hopkins is one such center. We are soon going to open a multi-institutional study involving Duke
University, Weill Cornell Medical Center, Memorial Sloan Kettering Cancer Center as well as Dana-Farber Cancer Center.
So these five hospitals are going to be collaborating on a prospective study that offers AR-V7 testing and then tries to
determine the clinical significance of the AR-V7 test in the setting of abiraterone, enzalutamide and taxane
chemotherapies.
So at the present time, the best way of having the AR-V7 test performed is to be seen at one of those institutions. And
hopefully in the near future we and others will have the capacity to be able to receive blood samples from out of state, from
different institutions and different practices, and to obtain the result and send it back to the patients. But at this point in
time, we're not quite there yet.
Andrew Schorr:
Any final thoughts, doctor, on where we are now and where we're headed in the treatment of advanced prostate cancer?
Dr. Antonarakis:
So I strongly believe that we are at a great and very exciting time with a lot of promise and progress going on in the field of
advanced prostate cancer. And, you know, all you have to do is take a look around at the drugs which are already available
right now and FDA approved. We have two novel hormone therapies. We have an immunotherapy, sipuleucel-T, which
acts in a totally different mechanism. We have bone-targeting therapies. And now we have radium 223, which is a liquid
form of radiation therapy that binds to bones.
So it's truly a very exciting time where we have a number of different drugs, each of which is targeting a different pathway
in the prostate cancer process. And the key will be how do we use these drugs in the optimal sequence, in the optimal
combination so that our patients can get most of these drugs or all of these drugs in the most rational manner possible.
And secondly, can we develop biomarkers that will help us personalize therapy. So the buzz word right now is all about
personalized medicine, personalized oncology and precision oncology. And so my dream would be in the next three to five
years that we would have blood-based biomarker tests available that will tell us ahead of time, in advance, which patients
should receive which therapies in which sequence. And I think that day will come, and I have a lot of optimism for the
future.
Andrew Schorr:
Dr. Emmanuel Antonarakis from Johns Hopkins, thank you so much for being with us on Patient Power once again.
Dr. Antonarakis:
Thank you very much.
Andrew Schorr:
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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors,
partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor.
That’s how you’ll get care that’s most appropriate for you.