Prostatepedia

Conversations With Prostate Cancer Experts


Leave a comment

Clinical Trial Eligibility + Black Men

Ms. Marie Vastola is a Clinical Research Assistant in Radiation Oncology at Dana-Farber/Brigham and Women’s Cancer Center. She works on Dana-Farber-led and international clinical trials that accrue men with multiple stages of prostate cancer. She is an author on six research articles focusing on prostate cancer and has presented her research at a national conference.

Dr. Paul Nguyen is an internationally recognized expert in prostate cancer clinical care and research. He has published over 250 original research articles and has various national leadership roles and is the Dana-Farber Cancer Center Genitourinary Clinical Center Director for Radiation Oncology, Vice-Chair for Clinical Research in the Department of Radiation Oncology, and Associate Professor at Harvard Medical School.

Prostatepedia spoke with them about how eligibility requirements for prostate cancer clinical trials may unfairly exclude African American men.

How have black men been underrepresented historically in prostate clinical trials? What are some of the prevailing theories or ideas about why that might be?

Dr. Nguyen: It’s multifactorial, and that was something that our research aimed to get at. Because of the historical experiences like the Tuskegee experiment, some African- Americans may have been more leery of engaging in clinical trials. Because trials require certain costs and extra time away from work, this can be more difficult on certain populations. Or it could be from the doctor side. Some doctors may not be as willing to engage African-American patients to enroll them on trials. There are multiple factors, so it’s hard to know exactly what is the main driver.

Ms. Vastola: We have patients come from long distances to Dana-Farber, and they do that because they know that Dana-Farber is a good place for them to get treated. Many patients, especially ones who travel long distances, either have connections in the medical field and that’s how they found out about this, or they’re highly educated and they have the resources to look into research and potential treatments themselves. These are tools that only people who are a little more privileged have.

Why did you zero in on eligibility criteria? What were you looking at?

Ms. Vastola: Actually, a patient is what started this research project. I had been screening an African-American patient for one of our open trials, and filling out the paperwork to determine if he was eligible. Most of this paperwork is related to the cancer, to make sure that patients have the type of cancer that we’re studying. But other sections of the checklist establish that the patient is otherwise healthy. We wouldn’t want to give an experimental treatment to a patient who wasn’t healthy for their sake and for the research’s integrity. He didn’t meet the criteria for one of those health checks.

One of the ways we determine that a patient is otherwise healthy is to look at their immune function, and his white blood cell count was too low. I hadn’t seen that before, and we ran his blood test again. His medical oncologist said the patient had benign ethnic neutropenia, which I had never heard of it until then. Because of that he couldn’t go on the trial that we had. It wasn’t a trial that we were running out of this hospital, but we talked to the sponsors. And as with many big trials, they don’t allow exceptions, no matter what.

He didn’t get the opportunity to be on a trial that was designed for men just like him, and that was really frustrating. Everyone involved with his treatment was frustrated with that, and so we looked into if that could be happening to other men. We also looked at creatinine. It’s well known in the medical field that black patients have a higher serum creatinine, and so you have to use a special formula that accounts for race when you’re looking at their kidney function. We looked at benign ethnic neutropenia because that’s what started it, and it was something that people seemed unaware of.

Dr. Nguyen: In a research group, the ideas usually come from the lab principal investigator (PI), and then the junior people carry it out. In this case, Marie actually came up with this idea herself because of a patient experience that she had, seeing an African-American patient not be able to get on one of our trials. It’s what led to this Journal of the American Medical Association Oncology paper, which is impressive.

That is. What did you look at?

Ms. Vastola: We wanted to know how often this happens. Was this a fluke, or does this happen to other African-American men? The best way to find out was to look at the eligibility criteria of other trials. Every trial records when people don’t meet the criteria. They don’t often record why though, so we couldn’t just look at the internal records of our trials. The website clinicaltrials.gov lists all trials available to patients in the United States and also a lot of international trials, and it usually lists the eligibility criteria. Not all the trials go into detailed criteria, but many do. We went through 401 trials that had endpoints that we thought meant that they had the potential to reach large audiences and change practice. We looked at all of them and pulled the eligibility criteria to see how many of them had this white blood cell criterion.

We expected some would have it. We did not expect that almost 50% of trials would have either of these two criteria. We were also surprised that the serum creatinine criterion was so common that a quarter of the trials have it.

People are aware of this, and they know to calculate kidney function accounting for race. A lot of trials would use serum creatinine, which is just the blood test, but then they would also say that if a patient meets formula criteria (based on race), then they’re okay, which is what we want to see. Not all trials do that, and that’s the issue. Every single lab result you look at that measures creatinine says at the bottom that if the patient is African-American, apply this formula. But over 25% of these trials weren’t including that formula.

What else did you find?

Ms. Vastola: Those were the two criteria that we looked at. We also broke it down by year, size of the trial, the phase, and toxicity of the therapy. We were glad to see that, over time, people are using the serum creatinine eligibility criteria less and less, which may mean that more people are aware of it. That’s not the case for the white blood cell criterion though.

Dr. Nguyen: We looked only at trials that have survival as an endpoint, so these are trials looking to make people live longer. We think it’s especially important that all patients have equal access to these kinds of trials. There are a few consequences of not having African-Americans on these trials. Patients who go on trials can sometimes get access to new drugs, so it’s a problem if African-American patients aren’t getting on trials. We also don’t get to learn enough about whether certain drugs perform particularly well in African-Americans, and so we don’t get to learn about the specific benefits or lack of benefit of certain agents for African-American patients. We wind up extrapolating from the larger patient pool, which probably works most of the time, but perhaps there’s something special that we can learn from having African-American patients on trials so that we could find better cures that can be tailored for African-American patients.

Ms. Vastola: Exactly. Not having access to these clinical trials hurts the individual because they don’t have access to treatment that could potentially help them. But the lack of access also hurts the whole population.

It also skews your results, so that what you’re learning about isn’t really prostate cancer in all men, just prostate cancer in a subset of men.

Ms. Vastola: Exactly.

What do you hope this will mean for clinical trial design and eligibility recruitments?

Ms. Vastola: We presented this research letter at the Prostate Cancer Symposium of the American Society for Clinical Oncology in poster form. We got a lot of feedback from academic investigators, people who devote their lives to this. Their papers define the field. They said they’d never thought of this, and that some didn’t know benign ethnic neutropenia existed. This section of the eligibility criteria—the part that defines whether a patient is healthy—is just carried over from trial to trial because it’s so standard. It’s not something people think about when they design trials because it’s so standard.

It’s textbook. We hope that, as more people understand this, they will consider it when they design their trials.

Dr. Nguyen: We were guilty of it in our own trials, and that’s how this all came about. We just used standard entry criteria copied over from previous studies. We were surprised to learn that this could disproportionally disadvantage African-American patients from being able to enroll in our trials. Given all the barriers that African-American patients face in getting on clinical trials in the first place, the last thing that we need is yet another barrier.

Not a member? Join us.


Leave a comment

Prostate Cancer, NIH + Clinical Trials

Dr. Ravi Madan (@Dr_RaviMadan), the clinical director of the National Cancer Institute’s Genitourinary Malignancies Branch, focuses on immune stimulating therapies. In particular, he’s interested in how we can combine these approaches with other therapies to improve patients’ lives.

Prostatepedia spoke with him about clinical trials for prostate cancer patients.

Why has it been difficult for doctors to enroll patients in clinical trials?

Dr. Ravi Madan: The reasons vary from case to case. Sometimes physicians don’t mention relevant trials at the right time for patients (when they’re making treatment decisions). Sometimes patients don’t want to go through the process of enrollment because of the perception that it delays their care and that delay will somehow impact their outcome. There is also personal preference. Some patients really don’t like the uncertainty of a clinical trial—uncertainty in terms of what their treatment will be if there’s a randomization or uncertainty about the outcome.

Trials should be discussed with patients when they’re making a decision to change therapies. While enrollment does take time, it’s usually only a few weeks, and for the most part, that doesn’t impact the patient’s outcomes or overall course. Ultimately, patients need to have a risks/benefits conversation with their doctor to determine if a clinical trial fits into the personal treatment strategy that they’ve developed with their doctor and their family.

Perhaps many people assume clinical trials aren’t really available until you have advanced disease, but that’s not really true is it? There are trials available at all stages along the journey.

Dr. Madan: Correct. Trials exist in all stages of the disease. The ones that often get the most notoriety, either on television or in the news, are the ones for late-stage patients. But for example, here at the National Cancer Institute (NCI), we have trials for every stage of prostate cancer, from patients who are newly diagnosed to early recurrence to non-metastatic, and then ultimately, late-stage disease.

Why would someone want to join a trial? Just to gain access to a treatment he may not otherwise have access to?

Dr. Madan: Sometimes you get access to treatments earlier than they may be available to the general public. People should understand that clinical trials often involve the standard of care they would get anyway plus an experimental agent.

There is an altruism component to a lot of this as well. It never ceases to amaze me, but when I deal with the patients here at the NCI, so many of them tell me: “If this helps me, that’s great, but I just want to help someone else later on.” It’s not like everybody has to have that reason, but it’s remarkable how many do. So, the reasons are variable. Sometimes it’s because there aren’t other options, but sometimes it’s because it adds options or adds cards to the playing deck, if you will, and sometimes it’s just pure altruism.

I guess that’s especially true in earlier-stage diseases, where you don’t necessarily need experimental treatment or access to something that you wouldn’t otherwise get access to, such as those on active surveillance.

Dr. Madan: Correct. We have patients in studies who just have rising PSAs where we’re trying to evaluate the potential of immunotherapy in that setting, but the alternative therapy is just really observation for a lot of those patients. For them, the trial is an opportunity to do something when the standard of care might be to do nothing.

What about the concept of the placebo? I’ve heard patients say they’re afraid of getting a placebo, which could make their cancer worse. Is that still a part of the clinical trial world?

Dr. Madan: It is part of the clinical trial world. Many trials require a placebo because in order to scientifically answer a question, there may have to be a group of patients who are untreated. In those circumstances, the protocol (a document that is often over a hundred pages) is designed to protect those patients. Whenever patients are on placebos, there are very strict guidelines about how they’re watched and the parameters used to remove them if there’s evidence that their cancer is getting worse. In some cases, they have scans very frequently. They’re not left unminded, and it’s usually for a short time.

But many trials don’t involve placebos. We conduct trials to see if we can take a standard therapy that’s in use and add something to it to make it better, and this is especially true in this new age of immunotherapy.

In that process, everybody will get the standard therapy, and some of the patients will get the experimental therapy in addition.

They’re not just getting a placebo, and then left unmoored.

Dr. Madan: Right. There are very strict criteria about how patients are monitored so that, if there is evidence that the cancer is getting worse—regardless if it’s standard therapy or placebo—then they move onto something else. In many trials with placebos, oftentimes the physicians don’t even know what the patients are getting, so the physicians often treat them all like they’re getting the placebo because that’s really the safest thing from a patient’s standpoint.

That’s interesting.

Dr. Madan: We need to monitor placebo patients closely in case they are getting nothing, and we need to move on to something else. But if a trial involves placebo, patients should be comfortable with that and comfortable with the relationship with their doctor who’s going to help them make these decisions. Otherwise, it creates a lot of stress, whether in the initial process with the randomization or while they’re on the study.

What about the financial end of trials? Do patients have to pay to participate in clinical trials—for the therapy itself, the procedure, the scan, or more? Or are the costs just travel expenses and time away from work?

Dr. Madan: Generally speaking, patients don’t pay the price for the drug treatments on a clinical trial. Sometimes trials are billed so the insurance company will cover standard costs that would be covered anyway. But for the most part, the patients do not incur the cost of the clinical trial. Costs are borne out by the companies or research bodies that conduct the trials.

Here at the National Cancer Institute (NCI), we are able to conduct trials that are completely free of charge to the patients. And in addition to that, because we are a government entity designed to really benefit the entire country, once patients are enrolled in our trials, we are able to fly them in from different parts of the country.

We can incur the travel costs for patients who travel from anywhere in the United States. That’s part of our mission here: to bring the benefits of this institution to everyone in the country.

Wow! So your clinical trial patients only have to pay for their hotel and time away from work?

Dr. Madan: Correct. And most patients qualify for a subsidy toward their hotel.

That’s unusual, isn’t it? Most non-government- funded trials don’t offer things like that, do they?

Dr. Madan: Yes. It’s an unusual circumstance. It allows our institution to address diseases that may not affect many patients within one geographical area. It’s a unique opportunity to conduct studies on rare diseases, but we also use it for studies in more common diseases.

You don’t want to just study prostate cancer in men in the metropolitan D.C. area, right?

Dr. Madan: Correct. For example,

I have studies with medullary thryoid cancer, which is a very rare disease. But we’re able to get people from across the country and do it in a way that no other institution can because our catchment area is the entire country.

How can men find out about clinical trials? My impression is that the usual path is that their doctor brings it up, or perhaps they hear about it in a support group, but what are some ways that men can find out about trials? Just by visiting clinicaltrials.gov?

Dr. Madan: I would actually recommend https://www.cancer.gov/about-cancer/treatment/clinical-trials/search because clinicaltrials.gov is more for clinicians. One of the greatest features of cancer.gov is you can search by zip code or city, and it tells you trials within 25, 50, 100 miles, or whatever you like. But either website has a great patient-based resources. I encourage patients to bring up clinical trial options with their doctors and get their doctors’ thoughts on what they find.

Patient support groups are another excellent resource. Depending on the cancer, there are also online support groups that are more prevalent and will probably become more so. Over about a third of our patients are self-referred from around the country, and not just referred by doctors, so it’s common for patients to advocate for themselves in this manner.

I was under the impression that if, for example, a man found one of your trials on clinicaltrials.gov and thought he was a perfect fit, he had to go back through his doctor to get involved in the trial. Is that true? Or can he contact you or the researcher directly?

Dr. Madan: Yes; he or she can contact the researcher directly. I get some calls directly from patients saying they saw this on the internet. We also have a clinical trials contact, so no, they don’t have to go through their doctor. I often encourage patients to speak to their doctor just to get an impartial perspective or additional perspective.

Also, patients and doctors have very good relationships usually, and it’s important to get a second opinion before you embark on the clinical trial journey.

But certainly they can contact us directly, and they very frequently do.

When studies are finally completed and published in academic journals, are patients informed, or do they have access to those results?

Dr. Madan: There’s not often a direct mechanism by which patients are informed about the results of the trial. But often, through the course of a study, patients will ask about the experiences so far. We’ll certainly fill them in, and then we have had patients call us up for results. We certainly publish the results and can share them, but there’s not a direct mechanism.

Interesting. There probably should be.

Dr. Madan: That’s an interesting idea. It’s possible some institutions have that. I’m not aware of any at this time.

But patients can always ask their contact directly, right?

Dr. Madan: Yes.

What else should patients know about joining clinical trials?

Dr. Madan: Clinical trials can be an important part of each patient’s individual treatment strategy. Especially for patients with cancer, it’s important for them to develop these strategies in conversations with their doctor and their families, and to develop that strategy based on personal preferences.

Clinical trials are a way to get additional treatment options over time, options beside the standard options that are generally available. Being on a trial requires a little additional time, and there is potential for side effects. If there’s a randomization process, patients should be comfortable with that, no matter what they get.

As the patients who come to NCI from all over, consider local trials and those around the country. Sometimes travel is not optimal, but we’ve had patients come in from as far away as Hawaii and Alaska. Take advantage of the opportunity if you can. The pace of cancer research today is remarkable, especially in immunotherapy, which is one of the biggest focuses here at NCI.

All of us should remember that none of these advances would have happened without remarkable patients who decided to enroll in clinical trials. I consider it an honor to be able to work with the types of people who enroll in trials here at NCI and around the country. It’s really an extraordinary and humbling experience for me.

Not a member? Join us.

 

 


Leave a comment

Funding Clinical Trials

Dr. Jonathan Simons is the driving force behind the Prostate Cancer Foundation, one of the leading funders of prostate cancer research worldwide.

Prostatepedia spoke with him about what clinical trial participation can do for your own prostate cancer journey.

Join Prostatepedia to read more about prostate cancer clinical trials.

How did you become involved with prostate cancer advocacy and the Prostate Cancer Foundation (PCF)?

Dr. Jonathan Simons: When I joined the Johns Hopkins faculty in 1993 as a young assistant professor, perhaps six laboratories in the world had prostate oncologists trained in molecular biology. Johns Hopkins did not have even one clinical trial in advanced prostate cancer using a medicine actually designed to fight the disease.

Then I met Mike Milken. He’d been diagnosed with advanced prostate cancer and was seeking third and fourth opinions—not only about his own case, but the state of prostate cancer research in general. Mike wasn’t new to medical philanthropy; he’d been funding a broad range of research for decades before his diagnosis. But he was new to prostate cancer, so it was encouraging when he left our meeting saying there would be an infusion of research funds and a foundation to make progress against this disease. My mentor and research director at Johns Hopkins, Dr. Donald Coffey, told me, “If anyone’s going to change this field, he’s the guy. I didn’t realize that later I’d end up being PCF’s CEO and President.

You were quite young.

Dr. Simons: I was an Assistant Professor eight months on the Johns Hopkins faculty, and I had a six-year-old and a four-year-old son running around in my office with coloring books on weekends while we set up experiments in my small laboratory. Back then, I was funded by PCF from across the hallway. They were within shouting distance. I have now a 30-year-old and a 28-year-old who do not use crayons.

What year did you officially join PCF?

Dr. Simons: I was there at the beginning in 1993 and was invited to the inaugural celebration of the founding in Washington, DC. Early funding from PCF allowed me as a physician-scientist to train in my laboratory another generation of young investigators who have gone on to become chairpersons and full professors at leading cancer institutions. Today they work toward better precision treatments and cures for prostate cancer in fields ranging from molecular biology to drug development, early clinical trials and nanotechnology. In 2007, I was recruited from the Emory University Cancer Center as its Founding Director and appointed CEO and President of the Foundation. I feel an awesome responsibility and the privilege to continue to serve the field in this way.

PCF funds quite a bit of research, both in United States and abroad. Is there a theme behind the kind of research you fund? What is your overall strategy?

Dr. Simons: The overall strategy is to fund the world’s best, most innovative ideas early enough to reduce deaths from prostate cancer, reduce suffering from prostate cancer, and ultimately eliminate prostate cancer as a plague on humanity. What that means, though, is that we fund mostly laboratory-to-clinic, game-changing, early-stage research in university and cancer center laboratories. We find partners to leverage this funding with additional government or biopharma support. We also fund research to help guide those therapies into the clinic to test whether they are successful or not.

If the treatment shows promise, we try to leverage further the tens of millions of philanthropic dollars that we put in at the beginning with hundreds of millions more from Department of Defense, National Cancer Institute, Stand Up 2 Cancer, the V Foundation, and private foundations. About 80% of what we fund is precision treatment science, 10% basic biology, and perhaps 10% prostate cancer prevention including precision nutrition research.

Additionally, PCF was established with more in mind than accelerating cure for prostate cancer. From the beginning, we aspired to change the face of cancer research and to produce results that could help people suffering from a broad range of serious diseases. We never saw the process as a zero-sum game where increased funding for one disease diminished support for others. Rather, it has always been one of our key goals to increase the size of the research pie in ways that would benefit the greatest number of people.

Your organization funds the beginning idea—sparking research—and then other organizations like pharmaceutical companies or research institutes take the ball and run with it?

Dr. Simons: That’s exactly so. Spark, instigate, cultivate scientific proof-of-concept, and convene stakeholders to ensure there is a strong ecosystem to take those concepts forward for patients.

You partner with pharmaceutical companies. You partner with medical institutions and the United States government. What about other countries? Do you work with groups in other countries?

Dr. Simons: We fund research in 21 countries. We have working partnerships with five foundations. We usually lead invest, but we are delighted to co-invest in research, particularly new kinds of treatment. We should really be called the Global Prostate Cancer Foundation.

It has been difficult for researchers to get patients to enroll in clinical trials. Why do you think that is? What has been the obstacle to getting men to participate?

Dr. Simons: It is complex. I wish I knew all the answers. I think one reason is that patients feel fear about receiving a placebo and about being a guinea pig. That almost never happens in the kind of treatment research that we fund.

But I also think there is a lack of access to information about trial availability. I still think patients aren’t empowered to ask which clinical trials could help them have a better outcome and also help others. I don’t think the system is proactive. (Crate and Barrel bothers me a lot more about their products than the National Cancer Institute bothers patients about whether or not they might be eligible for a precision medicine trial.)

We’re trying to increase awareness of these newer precision medicine clinical trials that have a much higher probability that the drug will work because the target gene is expressed or mutated. Basically: your tumor is vulnerable now and we’re getting access to it, so the investigational drugs have a real chance of getting you back into remission. I think those are the major challenges.

Another issue is distance and travel time and associated costs. Clinical trial participation goes way down if it takes the patient more significant time to get to the hospital. If you are enrolled in a clinical trial, you have to go back and forth more often to see the doctor and nurses monitoring you. With a longer commute, participation rates fall. We’re therefore very interested in telemedicine, or using the internet, so patients don’t have to drive as much. That’s still experimental. Dr. Matthew Galsky, from Mount Sinai, is working on that problem.

Using telemedicine in clinical trials?

Dr. Simons: Yes. Most everything in the clinical trials world is still analog, and yet we live in this extraordinarily digital age. I’m talking to you on my phone—a piece of glass with some metal off ultra high frequency radio waves. Right before this call I was looking at an MRI scan on my iPhone. I can do that, but we still make patients drive 90 minutes to see a doctor when we could probably use a smartphone.

There are a lot of ways we could very reliably take care of patients in an outpatient fashion. We just haven’t fully digitized clinical trials, particularly for patients at a distance. There are a lot of ways to innovate around digital healthcare that would help make clinical trials easier for prostate cancer patients.

I think some men assume that a clinical trial might not be an option until their cancer has advanced. They wait until things have gotten really bad and then they look for a trial. I don’t get the impression that many people think about trials when they’re first diagnosed.

Dr. Simons: No.

But there are trials for the newly diagnosed, aren’t there?

Dr. Simons: Absolutely. And a lot of them offer the possibility of much greater longevity and survival. Your instinct should be: where is the right clinical trial? But you’re still processing, thinking, “My God, I have cancer!” We could do a much better job of educating patients.

How do most people find out about clinical trials? Just waiting for your doctor to say that she has found a trial you might want to consider? Or is the burden on the patient to find the trial?

Dr. Simons: Most of the time, if your physician isn’t a real champion, it’s just not a part of the consultation. Most clinical trial enrollment happens because you have a urological oncologist who believes in putting patients on clinical trials and is probably participating in one. We’d like patients at every stage in their journey to look for a clinical trial with the idea that it might offer a better plan of care than they would otherwise have. We could also do a better job of encouraging nurses to talk with patients about clinical trials.

How would you suggest men look for trials?

Dr. Simons: The site http://www.clinicaltrials.gov is an excellent place to look. I think www.PCF.org is an excellent place to look as well. Making a habit of asking your doctor if there are any new clinical trials for where you are is also a great idea. Create the expectation that your doctor has to pay attention to potential trials.

The site http://www.clinicaltrials.gov tends to be a little bit technical. I would think it might be difficult for the average person to sort through.

Dr. Simons: You can always just ask your nurse or doctor about it. But I agree. We put more than 82 cents on the dollar into our research mission every year. But we wish we had the resources to create an incredibly patient-friendly, readable, real-time, digital website for clinical trials. Until somebody does that, clinicaltrials.gov and pcf.org are good places to find the really important trials.

I suppose you could always come up with a list of trials and then bring it to you doctor and ask if any are appropriate for you.

Dr. Simons: Yes. For right now, that is the best thing to do. The first thousand men cured of advanced metastatic prostate cancer will all be on a clinical trial. That’s a true thing. This is how we talk to lymphoma patients. It’s just more and more possible to talk about it for prostate cancer.

Prostate cancer is undergoing a revolution that other cancers have already gone through?

Dr. Simons: We’ve cut the death rate down by 52%. That’s incredible. For the last 48%, we’re going to need clinical trials. We need patients on clinical trials to take the death rate to zero. Sometimes prostate cancer, unfortunately, escapes surgery or radiation and comes back. While we’ve significantly increased the overall survival rate, we’re not yet able to cure the majority of men. We think we can. We know we can, but we have more work to do.

What does the financial end of clinical trial participation look like? Do men have to pay a fee for the therapies?

Dr. Simons: In clinical trials, research drugs are always free. Medical care is always free. The inconvenience is what is costly. Some employers are very difficult about you missing work for a clinical trial. There is a lot of going back and forth. They call it wage and financial toxicity. One of the effects of the experimental drug is toxic to job security. (It’s hard enough when you’re a cancer patient and worried about your employer.) But the drugs, the pharmacy, the medical care, and the scans are all free.

Is there anything else you think patients might want to know about clinical trials?

Dr. Simons: The misperception is that patients will be treated like guinea pigs. But the first thousand patients cured of prostate cancer will all be on a clinical trial. Every major clinical trial is changing prostate cancer patient survival.

For example, in the SPARTAN trial for Erleada (apalutamide), the drug was so effective that within two weeks of presenting the results, it was FDA-approved. That’s a record. Data was presented showing that 800 patients were benefitting from the drug, and then it was approved.

The only drug that gained approval that quickly in all of oncology was Soltamox (tamoxifen) for breast cancer. We think this is going to happen all the time now.

The SPARTAN Trial focused on patients for whom previously there were no treatments. They saw their PSAs going up, but they were not metastatic. There was really nothing for them to do except wait until we started seeing metastases.

Now, with Erleada (apalutamide) there is a chance that they’re not going to see metastases for years. They’ve got hope. For that first group of men, all of this is possible because they found that clinical trial. Hundreds of men who participated in the SPARTAN trial are going to have a prolonged time without metastases.

Would you encourage newly diagnosed men to seek out clinical trials, even if their cancer is under control?

Dr. Simons: Yes. I encourage every patient to think about joining a clinical trial. It’s not an easy message, but there are many studies showing that you get better nursing just by being on a clinical trial. You just get more attention. You can be there for the cure.

Not a member? Join us.


Leave a comment

Prostate Cancer Clinical Trials

Dr. Charles Myers frames our May conversations about prostate cancer clinical trials:

Over the past ten years, the management of prostate cancer has been revolutionized by the appearance of new drugs and new concepts using established drugs as well as surgery and radiation. Every one of these advances only exists because of clinical trials. This is the only path forward. This month, we discuss many of the issues patients face when they consider entering a clinical trial.

The fact that most large clinical trials include a randomization to a control arm is often a major source of patient concern, especially if the control arm uses a placebo. When the control arm involves an active treatment, that treatment will typically represent current state-of-art care that you might receive if you do not enter a clinical trial. However, the cost to you will be less because the clinical trial sponsor will commonly cover the cost of care. The financial benefit to you could easily reach thousands of dollars.

What if the trial includes a placebo arm? First, the existence of a placebo arm commonly indicates that no existing treatment has proven to be of benefit. As a patient, you should do your due diligence on this point. Second, there are strict rules in place to protect patients on the placebo arm. You should know these rules and make sure you are comfortable with them.

Patients on a trial’s placebo arm commonly do better than similar untreated patients not on a clinical trial. There is actually a large literature on why the Placebo Effect exists.

One explanation offered is that patients on the placebo typically get better standard care, and I think this is a major factor. It may also be that patients on placebo do better for psychological reasons or a mind-body effect. The latter might be particularly relevant for the treatment of nausea, pain, anxiety, or depression.

Finally, many patients enter clinical trials for altruistic reasons. By entering a well-designed clinical trial, you will help answer questions that will benefit future patients. The progress we have made over the past decade only happened because patients who came before you chose to enter clinical trials.

Not a member? Join us to read our May issue on clinical trials.

 


Leave a comment

Patients Speak: I Had Genomic Testing

Steve S. talks to Prostatepedia about how genomic testing gave him confidence that active surveillance was a safe choice for him.

Join us.

How did you find out that you had prostate cancer?

Steve: I don’t remember exactly, but I think I went to the urologist on the recommendation of a doctor who said I should have some PSA tests. I went to the urologist. The urologist ran some PSA tests and said, “They’re a little elevated. Maybe we need to run a biopsy,” which they did. That was about ten years ago. The biopsy came back with three or four cores indicating cancer with a Gleason score of 6 (3+3), which has remained the same over the last ten years. I think that’s what happened.

What kinds of genomic tests did you have and when?

Steve: That happened about five years later. I went to a support group and I heard about genomic testing. My doctor at the time hadn’t mentioned anything about genomic testing to me. I said to him that I didn’t see any downside in having genomic testing. Why couldn’t I have it? He said that he didn’t think it would be covered by my insurance and it’s not something they had done. I felt like a little bit of a pioneer.

I actually got on the phone with the people at Genomic Health in California and asked how much the test would cost. They mentioned a figure of about $500. I asked, “So that’s what I’m going to be charged?” They said, “Probably.” They weren’t really clear about it. In the end I was never charged.

They sent three results to my physician after a few weeks. Because my physician had never given them instructions as to what risk category he felt that I was in, they sent back three results based on different risk profiles. To this moment, I still don’t know exactly which risk profile I fit into.

All three results looked somewhat encouraging to my layperson’s eyes. I discussed the results with the doctor at the time and he said, “I think this confirms what we’re doing at the moment is right. You can continue on active surveillance, but of course it’s your choice.” They will always say that….

The results definitely changed your treatment path?

Steve: I was already on active surveillance, although in the first two or three years, I was thinking about some form of radiation therapy.

We talked about seeds. We talked about beams. I even talked to a friend a few years older than me who had gone through proton beam therapy and he was very encouraged by his results. My insurance at the time did not cover that, so proton beam therapy came off the table. I was not thinking about surgery. I was turned off by the idea of surgery, even though they had a DaVinci robot.

Then I got the OncoTypeDX test. I looked at the results with my physician and decided to proceed. It confirmed what I was already inclined towards.

Do you feel like it gave you more confidence in your decision?

Steve: Yes. I think so. I think that’s fair to say.

Would you recommend that other men take these tests?

Steve: Everybody has a very different psychological makeup. For example, I’ve got a brother-in-law who doesn’t have prostate cancer, but is very educated on medical matters. He’s a smart guy, and so I talked to him about it. He said, “God, if it was me, I would take care of it right away. I’d have that prostate out of there and have peace of mind.” I responded with: “I’ve lost very little sleep over the years about it.” That’s just my makeup. It doesn’t bother me. I’ve got other things to think about, other things I care about. Health is very, very important.

I’m not a complete passenger in this process. That’s why it’s called active surveillance. I’m very careful about going to my doctor’s appointments, following up, trying to keep myself educated, and so forth. Would I recommend it to somebody else? Somebody else who has the same psychological makeup that I do? Absolutely. Somebody who is a nervous person, a Type A person, somebody who is likely to lose sleep? Perhaps not. I don’t see any possible downside to the testing, though. It’s another tool for you and your doctor to use to help you make your decisions.

Not a member? Join us to read the rest of this month’s conversations about genomics.


Leave a comment

Genomics + Prostate Cancer Care

Dr. David J. VanderWeele is an Assistant Clinical Investigator in the Laboratory of Genitourinary Cancer Pathogenesis at the National Cancer Institute. He is particularly interested in investigating the progression of clinically significant prostate cancer.

Prostatepedia spoke with him about how genomics impacts patient care.

Join us!

What is genomics, and how does it differ from genetics?

Dr. VanderWeele: Typically if you’re talking about genetics, you’re talking about an individual gene or a small set of genes. When you refer to genomics, you’re referring to all the genes or a very large set of genes. Genomics usually refers to the genes–the DNA sequence. But sometimes genomics is also used to refer to when those genes get expressed (as RNA), or to other changes to the DNA that don’t change the DNA sequence (also called epigenetics).

What do and don’t we know about why some men develop curable or indolent prostate cancers while some develop widely lethal diseases?

Dr. VanderWeele: A lot of effort has been put into trying to learn more about the genes you inherit from your parents and how that influences the likelihood that you’re diagnosed with cancer. Most of that effort has been unable to identify which alterations in your genes make it more likely that you will get an aggressive versus an indolent cancer.

As many of your readers probably know, many people get indolent prostate cancers. In fact, many autopsy studies have looked at patients who have died of other reasons and have never been diagnosed with prostate cancer. Once men reach their 70s or 80s, it looks like more than half of men develop prostate cancer. Of course, those are relatively slow-growing cancers.

The most information that we have now is that men who come from families with breast and ovarian cancer syndrome appear to be more likely to get cancer and more likely to get aggressive cancer. These involve BRCA1, BRCA2, and other DNA repair genes in a similar pathway. Though there aren’t FDA-approved therapies yet, there are trials suggesting that these patients are also more likely to respond to certain therapies approved for breast and ovarian cancer.

This is a pretty small subset of all the men with prostate cancer, but the percentages increase with any kind of measurement of aggressiveness. If you look at people with localized cancer, that percentage increases if you have high-grade cancer versus low-grade cancer. The percentage increases if you compare people with advanced castrate-resistant prostate cancer to those with localized cancer.

If you look at the length of time between a man’s diagnosis and when he dies, that rate increases significantly the shorter that time is. That is just looking at three of these genes, BRCA1, BRCA2, and ATM. If you look at a broader number of these DNA repair related genes, it looks like ten to twelve percent of all patients with castrate-resistant prostate cancer harbor a mutation that they inherited from their parents. It seems likely that for most of those patients, that inherited gene contributed to their prostate cancer.

That has led to some debate about how often we should test for mutations in these genes. Is that a high enough number that we should test everyone with castrate-resistant prostate cancer? Should we still rely on family history to provide guidance for which people should be tested?

Is it really expensive to test those men? Why wouldn’t you just go ahead and test?

Dr. VanderWeele: Depending on how you do it, testing costs have come down quite a bit.

But when you’re testing for genes that could potentially be passed on to your offspring, or that siblings or other family members may have inherited, there are implications for your other family members, not just for you.

Some members of your family may definitely want to know that information and think that more information is better. Others may feel that if they find out that they harbor that gene mutation, they will just feel like they’re waiting for the other shoe to drop. It’s not information that they’d want to know.

Generally, we advise people to get counseling to help them think through some of these issues before getting tested for genes they’ve inherited from their parents.

Do we know why some men respond to certain drugs and therapies and others don’t?

Dr. VanderWeele: There’s a lot of interest in that. There has been some progress made in terms of identifying the biomarkers that might suggest which patients are more likely to respond to which types of therapies. At this point, however, most patients still get treated with most therapies.

There are some genetic biomarker-driven therapies that look like they’re on the horizon. Patients with mutations in BRCA2, ATM, and related genes are more likely to respond to a type of therapy called PARP inhibitors, which are currently approved for patients with ovarian or breast cancer, but not yet for prostate cancer.

There was a single Phase II study that showed that patients who had loss of a specific tumor-suppressor gene called

PTEN are more likely to respond to a certain type of targeted therapy. There are larger ongoing trials to demonstrate that these are indeed predictive biomarkers for response to these therapies.

There are companies like FoundationOne and GenomeDX that look at the molecular features of a man’s cancer. Are those tests useful? What do they tell a patient?

Dr. VanderWeele: The FoundationOne test looks for mutations, deletions, or amplifications of specific genes that are relevant for a wide array of cancers. There are a lot of companies offering this type of sequencing.

Many hospitals offer their own version of it. A FoundationOne type of test can tell you if you have a mutation in BRCA2 or ATM. They should also be able to tell you if you have a deletion in PTEN. When they detect a mutation is present, however, generally they are not looking to determine if you inherited those changes from your parents versus the mutation being present only in the tumor cells.

These genetic tests are more popular in other types of cancers, because for prostate cancer there aren’t yet any FDA-approved therapies that would be given based on the results of these tests. These tests will become more popular as we make progress in demonstrating the benefit of these specific therapies and in our ability to predict which patients are most likely to respond.

If a patient reading this gets one of those tests, is it likely that his doctor is going to know what to do with the results? Will the results actually impact his treatment?

Dr. VanderWeele: There are probably a small number of patients who will have a result that will directly impact their therapy. At this point, the way that it would impact therapy is that it might suggest that they should find a clinical trial testing a specific type of drug.

I see.

Dr. VanderWeele: There are also other commercially available prostate specific genetic tests, like the one performed by GenomeDX, that are mostly aimed at men with localized prostate cancer who are trying to decide how aggressive their therapy should be. Typically, this means whether they should pursue active surveillance or get surgery or radiation.

Sometimes these tests are also used to determine if a patient should get radiation after undergoing a prostatectomy or if he should just continue to follow PSA numbers. The prostate specific gene expression tests are RNA-based tests, which are a little different.

They measure the levels of expression of a few specific genes. Tests like FoundationOne look for mutations, amplifications, or deletions of genes—which means they are DNA-based tests.

Tests like Decipher are more widely used now, right?

Dr. VanderWeele: Yes. They’re probably used mostly by urologists. My sense is that how often urologists order those tests and how heavily they rely on them versus other ways to predict the risk level of the prostate cancer varies quite a bit from urology practice to urology practice.

Subscribe to read the rest of Dr. VanderWeele’s thoughts on how genomics impacts prostate cancer care.


Leave a comment

Dr. David VanderWeele: Why Prostate Cancer?

Dr. David J. VanderWeele is an Assistant Clinical Investigator in the Laboratory of Genitourinary Cancer Pathogenesis at the National Cancer Institute. He is particularly interested in investigating the progression of clinically significant prostate cancer.

Prostatepedia spoke with him about why he became a doctor.

Join us.

Why did you become a doctor?

Dr. VanderWeele: Physicians come to the job through a number of ways. For me, it was both an interest in biology in general and in cancer biology specifically. I really enjoyed learning in undergraduate school, and later on in training, how cancer represents a normal biological process gone awry.

Of course, many people also have a family member who helped inspire their choice, either directly or subconsciously. My mother had breast cancer; I’m sure that was part of my internal motivation and interest in oncology.

How did you end up specializing in prostate cancer?

Dr. VanderWeele: I was interested in genitourinary oncology—prostate cancer, bladder cancer, kidney cancer, and testicular cancer—because there is a wide range in the natural history of those diseases and how we treat them. I became especially interested in prostate cancer in part because some prostate cancers are very aggressive and others are more indolent. The first step of managing prostate cancer is assessing the risk of the disease and not just treating all cancers the same way.

Subscribe to read the rest of Dr. VanderWeele’s thoughts on prostate cancer genomics.