Alan H. Bryce, MD, Mayo Clinic

 How do you feel when you hear about these advances, knowing that you participated and can see where the field is going?

 It excites me because, just last week when I was in your office after my regular series of blood tests and scans, that was my question to you. When and if in fact this does stop working for me, is there anything else out there new for me? You said, “Yeah, the next generation of treatments is just exploding. We have all kinds of things to talk about.”

It’s encouragement. The thing you always have to hang on to as a patient is hope. You’ve got to have hope, and you’ve got to listen for the encouragement because there are so many new options out there. And you need to find the ability to trust your oncologist and know that he is trying to lead you down the direction of, as Dr. Bryce says, putting him out of work—hopefully finding a cure for this prostate cancer. Honestly, I encourage every one of you to get into depth of what it is that’s going on with your particular type of cancer. Talk to your oncologist. Get as much information as you can. It will put your mind at ease. It will allow you to get a lot more sleep at night.

 That’s wonderful. Thank you for that, John. It’s always a pleasure to talk to you. The audience probably understands by now—you and I have been doing this so long that we’ve become buddies. Right?

: Any last words of advice for the people listening, the caregivers as well as the patients? You’ve already given some great advice, but any last thoughts?

 For the caregivers, just keep up the support. Do all the encouraging that you can. To the patients, trust your oncologist. Don’t be afraid of trying something new, finding what it is that’s out there that will work for your cancer. Because the worst thing you can do is be fearful of the disease. You must keep a positive attitude. You have to move forward every day, and your attitude has an awful lot to do with it.

 Very good. Thank you, John, for your friendship over the years and for your advocacy for patients. I also want to thank the people watching and the team at 

® for putting this together. For the patients and caregivers, thank you for your encouragement, for your courage, and your ongoing commitment to helping us find a cure for prostate cancer. Please help put me out of business. That’s the goal. No more oncologists. That’s the world we want to live in.

Videos

Advances in Prostate Cancer

 Let’s talk about the future of prostate cancer and where rucaparib fits into the current practice and where we see the next steps in the development of rucaparib—Rucabra is its trade name—in prostate cancer. Rucaparib is approved for the late-stage treatment of prostate cancer after one of the oral androgen pathway inhibitors, such as abiraterone or enzalutamide and after chemotherapy with a taxane, most commonly docetaxel. That ends up putting it as a fourth-line therapy, if you will, for men with prostate cancer who have this 

 mutation. That is part of the normal drug development process. There are practical and ethical reasons why we usually develop new cancer drugs in late-stage treatment rather than early stage.

The next steps are to start moving those drugs forward. We do the initial study late to get a clear, positive signal and know that we’re on the right track, but then what we start doing is start testing the drug in earlier stage, in combinations, start tweaking the dose, the regimen, finding ways to optimize the drug and make it more effective. Make sure we’re getting the most out of it for every patient.

In prostate cancer, those studies are ongoing. For rucaparib specifically, there is the TRITON3 study, which is testing rucaparib earlier, before chemotherapy, but after one of the oral androgen pathway inhibitors. In the future, you can fully expect that there will be lots of combinations with PARP inhibitors in prostate cancer. Many of those studies are already ongoing. I fully expect there’s going to be a steady drumbeat of data and results over the coming years as the cancer community starts to figure out ways to optimize these treatment options.

In my own practice, rucaparib is one of our standard drugs for the 20% to 25% of men with prostate cancer who have a qualifying mutation. It’s a big part of the population. Almost a fifth or a quarter of men are going to have the kind of mutation that makes rucaparib a good treatment option.

In our practice at Mayo Clinic here in Arizona, every man with advanced disease should have genetic testing, and in our practice every man gets it. We test his inherited genes, his germline genes right from the beginning. Usually from the first appointment we’re having that conversation. Then we get biopsies to test the tumor whenever there is a growing spot where we can easily get a piece of the tissue.

A key point here is that cancer evolves. By definition, cancer is a cell that’s mutating. The prostate cancer might look relatively quiet in the beginning, but after years of therapy, hormones, and chemotherapy, it can start to acquire more mutations and look different. An important point is repeat testing. As we saw in John’s case, his inherited genes were normal, but the tumor had the mutation. It’s not enough to just look at the inherited genes. We also must look at the tumor mutations. Then look at it again as the cancer evolves over time.

Future Use of PARP Inhibition in Prostate Cancer

 What support services or support structures do you have around you? You talked about your daughter, you talked about our relationship. Is there advice you would give to other prostate cancer patients or perhaps other types of support you would like to have or would have liked to have had in the past as one prepares for this journey?

I would like to have been closer to my twin sons too. My children are in their late 30s. Because of the frequency of my treatments, for the first year I tried flying back and forth from Alaska to Phoenix for my treatments, and then finally the expense of the flights just got to be too great. I was forced into making the decision that I should just relocate down here. I’ve been living here relatively close to your services for going on 10 years. Yes, it would’ve been nice to have the personal hugs and touches of your family, as opposed to being able to do it over the telephone. I’m very blessed. My family has always been very close. I can feel the love through the phone.

They’ve never once given me anything other than encouragement. You’re doing the right thing, Dad. I’m glad you’re where you are. We miss you, but the proof is in the pudding. The proof is in what has transpired with me—eight years ago saying I had at least three to five years to live. Well, here I am eight years later, and I feel as healthy as a horse. I wish I could control my weight a little more, but I have a great appetite. There are upsides and downsides, but nothing that I can point a finger to that would tell me that I should have done something differently. I really think that these new genetic treatments are the answer for some prolonged treatments for most of you who are out there under the same conditions that I am with the metastatic prostate cancer. I really believe in that.

Advice to Patients Facing mCRPC

 I’d like our viewers to be aware that there are now two PARP inhibitors approved. Six months ago there were none. Rucaparib was the first. There’s also olaparib. These two drugs are very similar. They’re both PARP inhibitors. They’re both pills. You take them both twice a day. The side-effect profile is fairly similar between them.

Because of some technical details of how clinical trials are designed and how the FDA approval process works, the approval labels on the two drugs are slightly different. They both target the same population. That is, men with castration-resistant prostate cancer whose tumors have specific mutations in these genes involved in the PARP pathway.

For my part, this was a long time coming. We have been doing this research for years when we started doing genetic research. We knew 

 was a good target. We knew this target was in prostate cancer. We knew that in breast cancer and ovarian cancer they’d already shown that these drugs worked. So much of what had to happen was convincing everyone—regulators, the industry, and ultimately patient advocates and patients—that this concept had to be brought over to prostate cancer, that it wasn’t just a concept that worked in breast and ovarian cancer. Ultimately that happened. This is an international effort from researchers in Europe, in the United States, and throughout the world to make this happen.

What’s really exciting in prostate cancer is that the pipeline of ongoing research of other drugs of other concepts and other modes of attack is brimming. There is a full pipeline of new concepts, some of them trying PARP inhibitors in other ways, moving them earlier in the disease course. There are two other PARP inhibitors being tested, some concepts that are completely different—the radiotheranostics and lutetium.

My goal as a medical oncologist is to put myself out of business. We want to cure prostate cancer so that no one has to deal with this again or ever go through this again. The great thing is that in prostate cancer, the pace of change right now is gangbusters. We’re seeing a couple of new approvals every year. The thrill, the happiness of every drug approval, never wears off. We are moving this field forward.

When you started on rucaparib, John, why did I recommend it for you? Obviously, it’s because it matched your genetics. I had a high degree of confidence that it was going to work.

Based on our conversation, what did you feel about the likelihood that this was a good move for you? As you go into a study, knowing that you’re an early adopter—that because it’s a study, by definition we don’t know exactly what’s going to happen—how do you think about defining success? And what was most important to you in that decision-making process?

 As the patient, not the doctor, not fully understanding the mechanics of this type of treatment, I relied on my discussions with you, but the people should know that when you’re volunteering into one of these researcher trials or studies, you’re coming in on a fairly regular basis for blood tests—extensive blood tests—bone scans, and CT scans on a three-month basis, much more frequent than would be normal for a patient with this type of cancer.

My concern was that with the earlier chemotherapies and pill forms of drugs, I was always watching. I couldn’t wait to see what my PSA [prostate-specific antigen] level was. Is it still low? It was almost at a point that it’s not negligible. You almost can’t even discern that it’s there, but with the other modalities, yes, it would start to rise back up. The conclusion would be, “Well, I think the cancers found an immunity to the drug.” This was a totally new concept. I wasn’t sure how I could identify whether I thought it was a good thing, a bad thing, how it was working for me. I relied on waiting to see what my blood tests were and what my scans were.

In a matter of three months of being on this PARP inhibitor, the increased size of my abdominal lymph glands shrunk down to normal size. The cancer was no longer visible in any of the soft tissue areas of my body where they were before. That to me was total success. I could tell that this treatment was working well for me.

The beauty of it all was far fewer side effects of taking this type of treatment than all the others prior to this. No loss of hair, no nausea, no general fatigue, no mood swings, no other things that would come and go with the other treatments. They were gone. I can tell you that I’ve been a full year now with virtually no symptoms and taking a drug that has totally kept my cancer at bay.

I am so encouraged by it. I want to encourage everybody out there to investigate it if in your process of where you are with your cancer, you’re ready for this type of treatment. Because there are some things that you must do prior to getting into a PARP inhibitor type of medication.

 That’s right. The FDA label talks about prior therapies as well. Indeed.

Alan H. Bryce, MD, Mayo Clinic

Advances in Prostate Cancer

Future Use of PARP Inhibition in Prostate Cancer

Advice to Patients Facing mCRPC

PARP Inhibitors in Recurrent mCRPC

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