Published on July 31, 2017
How can men with prostate cancer live better? Andrew Schorr leads a roundtable discussion with expert panelists, including Dr. Philip Kantoff, Dr. Daniel Petrylak, Dr. Sumit Subudhi and patient advocate Darryl Mitteldorf, to discuss how men with prostate cancer can live better while combatting treatment toxicity and side effects.The panel discusses how targeted therapy, vaccine therapy and immunotherapy could improve a patient’s quality of life.
This roundtable discussion is a Patient Empowerment Network program produced by Patient Power. We thank Sanofi Oncology for their support.
Transcript | Tools for Combatting Prostate Cancer Treatment Side Effects
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Dr. Petrylak, the therapies that we’ve had in prostate cancer have had toxicities, traditionally.
My father took one, and he had hot flashes. That was rough on him. Where are we now in developing medicines that could be more targeted, fewer side effects so that somebody can have prostate cancer but live better?
Unfortunately, we really have not made major advances in taking care of the hot flashes. But what we have made advances in are looking at molecular markers for different types of treatment. There is a molecular marker called ARV7, which is a splice variant of the androgen receptor. It’s the area where testosterone binds, has been removed, spliced out, and it’s constitutively active.
So giving certain types of hormones will not necessarily work in those patients. We’ve also looked at RAK and DNA mutations, DNA repair changes. Those can potentially mark for sensitivity to drugs such as PARPinhibitors.
So we may be able to spare toxicity and unnecessary treatment by focusing on molecular markers and using these to stratify patients as to what they should receive.
Okay, so he’s mentioning some PARP inhibitors and things that I’m hearing about in other cancers. So, Dr. Kantoff, are we getting to a place where you may identify something in a prostate cancer patient that has some molecular similarity to another cancer? Maybe there’s a medicine over there that has promise in prostate cancer. Is that the way it’s going to work?
Let me first address something that Dan mentioned and sort of speak to the patients out there about the concept of advanced prostate cancer. Advanced prostate cancer as we define it is cancer that’s come back after local therapy as usually defined by a rising TSA. The majority of those patients will not die of prostate cancer, and that’s an important thing for patients to realize.
And the majority of those patients will not require the hormonal therapy or what we call androgen deprivation therapy that is a treatment for advanced prostate cancer. So understanding that and sparing people the toxicity of hormonal therapy is something that we all need to be cognizant of. So getting back to your question about what we learn from other cancers, we’ve known for a number of years, probably a decade or two, that DNA damage repair is an important contribution to the development of cancer. Keeping the integrity of DNA is very important to not developing cancer
To make healthy cells.
To make healthy cells. Cancers develop when there is some damage to the system which repairs DNA.
DNA is constantly being damaged, and there are very sophisticated mechanisms that try to repair it. One of the most frequently aberrant systems that give rise to cancer is damage to one of the players that are involved in DNA damage repair. An example of this is BRCA in breast cancer, which was first discovered in the context of breast cancer, important in ovarian cancer, turns out to be important in other cancers as well; very important in prostate cancer.
We’ve found that about 25 percent of patients with advanced—and what I mean by advanced in this case are men with metastatic and resistant cancer—25 percent of the men have some abnormality in DNA damage repair. Astounding frequency that we did not recognize before.
It turns out that about half of them are heritable; they inherited them in the germ line. So these men had a lifelong tendency toward the development of not only prostate cancer but more importantly aggressive prostate cancer. Conceivably in the next few years we’ll be able to test for this. So getting back to your question and your point, we have to look at prostate cancer as prostate cancer, but we learn a lot of principles by looking at the science that is developing in other cancers.
I know it’s moving forward at this meeting. We’re hearing a lot about that across different cancers. So, Dr. Subudhi, one of the big buzzes for now a few years is the term immuno-oncology. And so if people in the United States see television ads, they see it for lung cancer drugs, and they’re hearing about it if they read the paper. Does it apply to others?
Does it apply to prostate cancer or a subset of prostate cancer patients, these so-called checkpoint inhibitors that can sort of either take the brakes off the immune system to go after the cancer or things like that?
Actually Dr. Kantoff here led the original studies with a therapeutic vaccine known as sipuleucel-T or Provenge. They’ve shown that in an unselected group of castration-resistant prostate cancer—these are all patients with metastatic and advanced disease—that patients who received it live longer than those who do not. And so this was the first proof that a therapeutic vaccine, not a preventive one but a therapeutic vaccine, can be successful. And prostate cancer is the first disease in which that’s been shown to be effective.
More recently, immune checkpoint therapies have gained a lot of attention, first in melanoma and most recently in other genitourinary diseases such as immunal cancer and bladder cancer. These drugs have been tested as mono therapies in prostate cancer and have not been shown to be effective in an unselected group of patients.
But as both Dr. Petrylak and Dr. Kantoff mentioned, now with these primocene biomarkers and having molecular characterization, we believe that we will soon be able to identify a subset of patients that may benefit from the immune checkpoint therapies. In addition, we believe that the immune checkpoint therapies in combination with some of the exciting drugs such as the PARP inhibitors may also play a role.