If someone you love or care for has been diagnosed with a life threatening illness, like breast cancer, and you are now thrown into a new role to help support them as they fight to survive, it can be overwhelming. It is not an easy task, by any means. And it’s a learning process. But if you’re like most people, you want to do the best you can to help your loved one through this journey. You’ll need knowledge, patience, resources and support of your own. It can also be helpful to connect with others who have gone through or are going through similar experiences with breast cancer.
Tatiana M. Prowell, MD is Associate Professor of Oncology in the Breast Cancer Program at the Johns Hopkins Kimmel Comprehensive Cancer Center and Breast Cancer Scientific Liaison at the FDA. She was the principal architect of FDA’s policy on accelerated approval using pathological complete response as a novel regulatory endpoint in the neoadjuvant high-risk breast cancer setting, and was a member of the Biden Cancer Moonshot Blue Ribbon Panel Cancer Immunology Working Group. She is a frequent public speaker and a three-time recipient of
FDA’s Excellence in Communication Award, a Giants of Cancer Care Award finalist, and the 2019 recipient of the John and Samuel Bard Medal in Science or Medicine. A passionate medical educator and mentor, she is Chair of the 2020 ASCO Annual Meeting Education Committee and
has served for many years on the faculty of the Vail Methods in Clinical Cancer Research Workshop, the Society for Translational Oncology Fellows’ Forum, the Dana Farber Clinical Investigator Seminar Series, and the FDA-ASCO Fellows’ Day Workshop among several others. She sees patients in the Johns Hopkins Second Opinion Breast Cancer Clinic and teaches in the medical school and medical oncology fellowship training program. Dr. Prowell received her BA degree from Bard College in Languages and Literature and her MD degree from the Johns Hopkins School of Medicine with election to the Phi Beta Kappa and Alpha Omega Alpha honor societies. She completed her residency and fellowship training at Johns Hopkins Hospital.
Adam: [00:00] Over the last forty years breast cancer treatment has greatly improved due to lessons learned through clinical trials. A clinical trial offers you the chance to try a new treatment and possibly benefit from it. Many new treatments for metastatic breast cancer are under study and most our drug therapies. Learning that a new drug is even better than a standard treatment regimen can also help others. To help us separate the myths from the facts let me introduce Dr Tatiana Prowell. Dr Prowell, welcome to the show.
Dr Prowell: [00:29] Thanks so much for having me.
Adam: [00:30] I’m really excited to talk to you. You know, drug trials are kind of a mystery I think to a lot of people and I’m really interested to hear more of your thoughts about it, but before we get into that can you tell us a little bit about yourself?
Dr Prowell: [00:43] Oh sure. So my name is Tatiana Prowell. I’m originally from Atlanta, Georgia and have been in Maryland now for about twenty-five years. I trained at Johns Hopkins all the way from medical school through the end of my residency and fellowship and I now am an associate professor at Johns Hopkins in the medical oncology department in the breast cancer program and the scientific liaison for breast cancer at the US Food and Drug Administration.
Adam: [01:10] Wow, that’s fantastic. Well, let’s dig into it. Help me understand can you define clinical trials and what that means?
Dr Prowell: [01:18] Sure. So when we say clinical trial we mean a research study where medicine or other intervention is being tested in patients who have a certain condition to see if that medicine will be helpful in their treatment. And there are a variety of types of clinical trials so some clinical trials everyone enrolled in the clinical trial gets the same treatment. Other clinical trials might compare an existing treatment to something new, but in all cases what we’re trying to learn is whether or not in the long run there’s a better way to treat patients with a certain condition than the way we do it currently.
Adam: [01:57] Okay and so there’s a lot of maybe lack of understanding or myths or misunderstandings about clinical trials. Can you just walk me through what are the biggest myths versus the most important facts and what should we really know about clinical trials?
Dr Prowell: [02:12] Yeah, so I hear lots of myths about clinical trials. I think that a common one that I hear, I hear this from my family members for example, some of my extended family, they’ll say I don’t want to be a guinea pig by going in a clinical trial. They feel uncomfortable with the idea that something new is being tried in them. That myth may come from phase one clinical trials so phase one clinical trials are usually clinical trials where a drug is being used in humans for the very first time, so it’s been tested in animals. We know what the side effect profile is in animals and we have an idea of the right dose that would be safe to start if we’re going to deliver that drug to people. And the purpose of those trials is to give successive groups of patients higher doses as they go along in the trial to the highest dose that patients are able to safely tolerate and I think that when we think of clinical trials sometimes people are envisioning that that sort of clinical trial is what we always mean when we say clinical trials, which is a drug where there’s no information about its use in humans.
[03:16] No evidence of whether it will be safe in humans, no evidence of whether it will be helpful for their cancer and there are definitely times when maybe we can get to this later in the interview, there are definitely times that phase one trials are appropriate for patients to enroll in, but the far more common scenario is actually not that. The much more common scenario is a drug where we already have some data in humans and maybe we’re using it in a different way, either at a different dose or in a different combination or in a different patient population and we’re trying to figure out ultimately can we produce better outcomes for patients than we’re currently capable of producing.
[03:55] There are a lot of safeguards in place put in place by the investigators who design the clinical trials and conduct them, but also regulators who oversee the development of all drugs that are being considered for ultimate FDA approval and institutional review boards. There are a lot of safeguards in place and in fact, I think that if a patient is eligible for a clinical trial, meaning it was designed specifically for people like themselves, that’s why the eligibility criteria allow them to be in it. If they’re eligible for a clinical trial that’s actually the best place to get your treatment. I think the other myth that I commonly hear is that clinical trials are really for people who are out of options and again this sort of gets at maybe these phase one or first in human kind of clinical trials where that idea may come from.
[04:45] But the truth is that if you’re eligible for a clinical trial at the time of diagnosis, for example, maybe a clinical trial is a randomized trial that is being used, the company will hope to ultimately support FDA approval, that trial might compare our existing best treatment by itself versus our existing best treatment to which a new drug has been added. And so, in that case the person will be receiving the standard therapy no matter what, but they may also be getting an additional drug.
[05:19] Now it may turn out that the additional drug is better that adding the additional drug means better outcomes for those patients, but it also may mean that the additional drug just adds side effects and doesn’t actually improve the outcomes and that is the purpose of the clinical trial being done. But we shouldn’t give the impression that clinical trials are only for people who are late in the course of their disease who’ve had a lot of prior treatments and the doctor is out of ideas in terms of standard therapy that is definitely a myth. There are others, but those are the most common.
Adam: [05:50] Let’s just talk about some of the benefits for clinical trials for metastatic breast cancer patients. So what are those benefits that they should be thinking about as they’re considering participating in a clinical trial?
Dr Prowell: [06:03] Yeah, so thanks for asking about metastatic breast cancer patients in particular clinical trials, that’s another myth maybe, is that they’re only for patients with metastatic cancer and I realized it as soon as you said it. In fact, they can be for patients they commonly are for patients who have earlier stages of breast cancer for example, that’s been resected with surgery and we’re looking at whether or not we can prevent a late recurrence. But I do think that there has been a lot of emphasis on the early breast cancer experience or prevention or risk reduction of breast cancer and maybe not as much focus as there should be in popular press on the experience of patients with metastatic disease. So thank you for asking about them in particular.
[06:42] I think if we’re talking about the benefits to a patient with metastatic breast cancer of going in a clinical trial, there are really two things. One is, is there a benefit to the patient herself or himself in terms of how long they’ll live with their breast cancer or how long they’ll be able to stay on a given treatment before they have to switch and go onto another treatment because the cancer has gotten worse. There’s also an altruistic part of it though and I think that really is a point that should not be lost. Everything we know about how to treat breast cancer comes from clinical trials and it comes from patients who went in clinical trials before us and so we owe them a tremendous debt of gratitude and having a diagnosis of cancer is so hard, and having a diagnosis of metastatic cancer in particular is so hard and what I’ve heard from many patients is that participating in a clinical trial brings meaning to their experience as a patient. And that matters a lot.
[07:42] No one wants to be in this situation and I don’t believe that everything happens for a reason in the trite sense that it’s usually offered that some unequivocal good will come out of this. I don’t think that that’s true. I think a lot of people suffer with metastatic cancer and that’s just a fact. I do think that being in a clinical trial allows a patient to feel that she or he is giving back and it brings meaning to that experience.
Adam: [08:12] Right, wow. I really love that perspective that’s kind of a beautiful thing even though it’s a very tough thing. Okay, so in considering clinical trials what questions should someone ask a research team before joining?
Dr Prowell: [08:27] The clinical trial is a tremendous commitment on the part of a patient. There’s a commitment of time, which really cannot be emphasized enough. Patients have additional study procedures as additional visits. There’s sometimes cost to the patient. Cost in terms of things like the study drug usually are not an issue because those are covered by the clinical trial, but there’s cost in terms of missed work. There’s cost in terms of needed childcare, so if patients are going to be in a clinical trial I think that they need to understand what’s being asked of them. Not just the medical risk, if you will, that they’re taking by being in it, but what is going to be the cost to them in their personal life, so to speak. If one has decided that being in a clinical trial is not an excessive burden on time and okay we’re committed to doing this, then how do you choose between them and there I think that it’s important to know what phase of clinical trial this is.
[09:31] For example, is this a drug that’s being tested in humans for the first time? If so, why does a doctor think it might be appropriate for me to be in that clinical trial now at this stage of my breast cancer? For example, is it because we’ve exhausted all the standard treatment options and this is a reasonable idea to try. Is it because there’s some marker in my tumor, for example, on testing the presence of a mutation or another marker that might lead us to believe that even though this drug is very early in development, that there’s good biological rationale for why it might be an effective treatment. Patients really want to understand the question that’s being asked because sometimes the questions that are asked in clinical trials are incredibly meaningful.
[10:20] So in the case of metastatic breast cancer does this drug help patients live longer? Does this drug reduce the chances of this cancer growing and spreading or prolong the amount of time until that will occur? Does this drug produce outcomes as good as our current drugs, but with fewer side effects? So those are questions I think are very meaningful. I think that in some respects shopping for a clinical trial is, is higher stakes, but not dissimilar to shopping for any other really valuable thing in your life. You want to do a lot of research.
[10:54] My husband and I talk about this a lot. He’s also a physician. He’s an HIV physician and both of our fields are scientifically and clinically and very complex. In 2019 we both feel like if we had to understand our car, for example, and how it worked nearly as well as patients have to understand their disease in 2019 to make treatment decisions or to decide to join a clinical trial, we probably would never get our cars fixed.
[11:21] You know we put a ton of trust in people and we just say, you tell me that it needs that part, okay. We don’t go do research on how do you know when the timing belt really has to be replaced? We trust that someone’s telling us the right thing to do. Patients need to be able to trust their doctors and their investigators. At the same time I do think it’s really critical for patients to get themselves educated as best they can to be able to make sure they’re making an informed choice because this is your life that we’re talking about.
Adam: [11:50] Yeah, that’s right and it’s striking that balance can be very difficult for patients. Trying to figure out how much do I research and how much do I trust and what’s the right balance in between those two, so, yeah, that’s a really good point. I appreciate you bringing that up.
Dr Prowell: [12:03]
Absolutely. Breast cancer’s interesting like that actually because that is part of why I love doing breast cancer specifically as a specialty. Breast cancer patients are so well-informed. They come with binders, with tabs, they’ve looked up articles, they’ve highlighted them, they have a whole page of questions. They are a uniquely organized and well-informed group and they don’t all come from backgrounds where they’re extensively educated or something like that. Certainly, some of them are, but some of them are not and nonetheless, I’m just constantly impressed by how well informed people with breast cancer are about their condition. By how much they can speak the language, by how much prior background work they’ve done before coming to a visit. It’s just incredible and I really tip my hat to them because I don’t know that I would be able to do that in another disease, for example, if I were diagnosed without the medical background that I have right so it’s really a credit to them.
Adam: [13:09] Well, and the nice thing is there’s a lot of great resources out there, including Komens resources and others where they can get a lot of really good information, which is part of why we’re doing this podcast too so that’s great. Well, so a few more questions related to clinical trials, who can join and how do they enroll? How does all that work?
Dr Prowell: [13:31] So that’s a great question, so in terms of who can join every clinical trial has something called eligibility criteria. So there are inclusion and exclusion criteria. The inclusion criteria are things that patients who are going to go on a clinical trial must have all love to be able to be in and the exclusion criteria are things that if they have even one of them, then they cannot join. And so examples of those things might be for inclusion criteria that you have to have metastatic breast cancer and that it has to have positive oestrogen and progesterone receptors and it cannot have [inaudible 14:08] expression in the tumor for example, and so if you have a different type of breast cancer or if you have another type of cancer entirely like colon cancer, you wouldn’t be able to go in that clinical trial.
[14:19] So that’s about helping us define the patient population and they are chosen to be able to enable us at the end when we get our results back, to know who do these results apply to. And then the exclusion criteria they can exist for a variety of reasons, but the most common reason that they exist is to protect patient’s safety. So for example, patients who have liver dysfunction of a certain degree might be excluded from a clinical trial because the drug is cleared out of the body through the liver and if the liver isn’t working properly, then the drug could build up in the patient and make it not safe for them or potentially not safe for them. One of the things that has been really terrific to see and, and I was so proud to be a part of this, along with a tremendous group of people is modernizing eligibility criteria for our oncology clinical trials.
[15:14] So there’s been for many years I think because everyone’s busy and no one likes to reinvent the wheel, there’s been a tendency to cut and paste eligibility criteria from one protocol to the next. Certainly, sometimes some of those absolutely can be cut and pasted. There is no need to reinvent the wheel, but this often leads to excluding patients who don’t need to be excluded because history has moved on. We have, for example, historically excluded patients with HIV from our clinical trials and that really reflects the fact that for many years patients with HIV had a limited life expectancy and we were concerned that enrolling them in our clinical trials if for example, the endpoint was overall survival. If they died, we could be confident whether that was a consequence of their cancer or a consequence of HIV and AIDS.
[16:08] I think that as we’ve made a lot of progress in HIV and in brain metastases and in many other conditions, it doesn’t make sense to be excluding these patients from clinical trials anymore. It’s anachronistic and so one of the efforts that several FDA staff including myself have been involved with along with the patient advocacy organization Friends of Cancer Research and American Society of Clinical Oncology, that published those recommendations in 2017 and they are increasingly being adopted. And so we’ve seen the National Cancer Institute modify their standard template for clinical trials to be consistent with those recommendations. We’ve seen a number of companies and cooperative groups and individual investigators embracing these recommendations and what’s exciting is this means we have now clinical trials available for a lot more patients who want to enroll in them.
[17:02] In terms of actually finding one this is something that we need to work on, honestly. There are clinical trials that are available in the community certainly there’s a large number of clinical trials that you can enroll in right from a private practice in the community, that that’s maybe another myth I should have addressed with the first question, which is to say you don’t have to be at an academic medical center to enroll in a clinical trial.
Adam: [17:31] Oh that’s great.
[17:32] That being said, for people that live far away from an academic center or who happen to be getting treated at a clinical practice that doesn’t participate in clinical trials and many do not, I think that that is a real limitation that we have not done as well as we could at getting patients into clinical trials by bringing the clinical trials to the patients. There’s an effort that’s underway now within the FDA and this has really been honestly a source of advocacy by a number of patient advocacy groups, but including the metastatic breast cancer community to decentralize clinical trials. To be able to have things like laboratory testing or imaging studies performed in the community whatever places is most convenient to the patient’s home or work.
[18:09] To be able to figure out can we use things like telemedicine for visits just like this. Can I as your doctor look at you and say, “Seem to be doing pretty well,” and ask you about the side effects that you’re having and then see you when I need to see you. But maybe that means you don’t have to travel this long distance to the clinical trial site quite as frequently. Is there an opportunity to use things like wearable devices to capture vital signs?
Adam: [18:51] I love that.
Dr Prowell: [18:52] This is coming and I’m very excited and I think that once that is fully realized, we’re going to have a lot more patients being able to participate in clinical trials and I hope that our clinical trials will accrue and give us results more quickly.
Adam: [19:08] I love that. That’s really good. I learned a lot just listening to this. This has been great. Well, Dr. Powell, this was great information. I really appreciate your time and thanks for being on the show.
Dr Prowell: [19:19] Thanks so much for having me. It was an honor.
Intro and outro music is City Sunshine by Kevin MacLeod. Ad music is Blue Skies by Silent Partner. The Real Pink podcast is hosted by Adam Walker, produced by Shannon Evanchec and owned by Susan G. Komen.