[00:00:00] Adam Walker: From Susan G. Komen, this is Real Pink, a podcast exploring real stories, struggles, and triumphs related to breast cancer. We’re taking the conversation from the doctor’s office to your living room
[00:00:17] We know that clinical trials are a critical lifeline, offering new ways to prevent, detect, diagnose, and treat breast cancer. Today, patient advocates are transforming clinical trials by bringing the real-world experiences of patients directly to researchers. By acting as a bridge between science and the community, patient advocates boost enrollment in clinical trials and help build a lasting trust.
[00:00:42] Today we’re speaking with Dr. Lior Braunstein, a radiation oncologist and researcher at Memorial Sloan Kettering Cancer Center, and Dr. Ellen Landsberg, a retired OBGYN and patient advocate, also at Memorial Sloan Kettering Cancer Center. Today, they’re working on the ARCHER clinical trial, a study that is investigating the new treatment strategy for HER2-positive metastatic breast cancer.
[00:01:08] We’ll talk about what they’re hoping to accomplish through the ARCHER trial, what their collaborative process looks like, and how new patient advocates in clinical trials can help improve patient outcomes. Doctors, welcome so much to the show.
[00:01:22] Thanks for having us.
[00:01:23] Dr. Ellen Landsberger: Thank you.
[00:01:24] Adam Walker: I love talking about clinical trials because they’re so important, and I love talking to patient advocates because they’re so important, so this is like a double win.
[00:01:31] I’m very excited about this. So I’ve got questions for each of you. So to, so to start Dr. Braunstein, this is for you. When an idea for a clinical trial is born, at what point is an advocate brought into the process, and how are they integrated into that process?
[00:01:48] Dr. Lior Braunstein: It’s a great question, and it, the answer probably depends, and it depends on an historical context too.
[00:01:54] So probably historically, the answer was that they were… advocates were brought in far too late really, if at all. And so the traditional model was that people would design the science, they’d lock in the protocol, and if an advocate was being brought in, it would typically be towards the very end, and they’d be asked to just sort of make sure the language was readable, and they’d sort of proofread things, and that was the extent of the function.
[00:02:14] But these days, I think there’s an increasing recognition that patient advocates can actually contribute a significant deal more to the design and the conduct of the study. So on the ARCHER trial specifically, we tried to do very much the opposite of what that historical setting was. So Ellen and our other advocate partners really joined at the conceptual stage, I would say, when the trial was still just a hypothesis.
[00:02:36] It was on the whiteboard. Basically, almost every important decision was still open, so that as we were getting that feedback- patient advocates who had a stake in the design and the conduct of the trial could could really influence what would happen. And the timing matters because the choices that most affect patients what we measure, how often people come in for scans or for blood tests and things, how we explain the risk, all these decisions are made early in the design of the study.
[00:03:00] And so once they’re settled in a protocol or once things have been sort of discussed and locked in, they’re very difficult to undo. So it’s critical to involve patient advocates early. We did that on the ARCHER trial specifically. This study is, has the benefit of being run through a group called the Translational Breast Cancer Research Consortium, which is a group of 18 major cancer centers around the country, and things are organized in such a way, and I think we’ll probably get to talk about this a little bit more, where patient advocates in a working group are brought on very early.
[00:03:33] So our advocates ultimately sit in the same design meetings as the statisticians and the surgeons and the medical oncologists and the radiation doctors, and they review all the eligibility criteria, they review the schedules, they discuss the burden of what it is that we’re asking of the participants, and they’re critically thinking about the questions that we’re looking to answer.
[00:03:52] So they, they have the standing to say that this won’t work for everybody, and you haven’t thought about something, or this is a blind spot of yours, and then we’re, as investigators, obligated to sort of take that seriously and to respond to those concerns. And so the goal is for the advocate to be sort of structural and woven into the design of the study itself rather than just a courtesy.
[00:04:15] And so that’s what we’ve tried to do here, and I’m, I- I’m hopeful we get to talk about that some more today.
[00:04:20] Adam Walker: I love that. I mean, it sounds like it gives gives you a lot more context as you’re designing the study because they have a very different perspective, I would imagine, right?
[00:04:27] Dr. Lior Braunstein: That’s exactly right.
[00:04:28] Different incentives, different burdens- a different viewpoint. Some investigators are patients themselves, and they can advocate in that setting, but many investigators are not, and then the experience of being on a trial can be something that’s totally foreign to the person who’s designing the trial, and so that’s why that voice is so important.
[00:04:44] Adam Walker: I love that. All right so, so Dr. Landsberger how did your own personal journey with breast cancer inspire you to become a patient advocate, and how did it influence your specific s- perspective as you began to come to the table for clinical trial design?
[00:05:01] Dr. Ellen Landsberger: That’s really an important question.
[00:05:02] I was diagnosed with early stage ER positive breast cancer in when I was 43 years old, and at that time, I was a practicing physician, I was academic in OBGYN and working really hard. I got my treatment, I worked throughout my treatment, and at the end of the treatment, I was ready to put breast cancer behind me Little did I know that breast cancer had a different plan for me.
[00:05:32] And 22 years later shortly after I had retired, I was found to have metastatic disease. And at that point based on my medical background and my learning in medical school, I thought I had two to three years left in life, and I– that’s all I could do, was think about getting treated and getting through this process.
[00:05:55] And I was really fortunate. I have I had oligo-metastatic disease, the word that was not mentioned at the time that I had the diagnosis, and I responded very well to treatment. So within a few months, I was working on scans that showed no evidence of active disease. And after about a year or two, I realized that I was doing very well.
[00:06:20] This was persistent, and I felt very obligated to give back to the community and to participate in this, that I understood the science, I understood the medicine, I understood the practicalities of being a patient, and it was, for me, a very easy transition to do this. And then I was– I spoke to my oncologist at Sloan Kettering, and the next thing I knew, I was being appointed as the MSK representative to this TBCRC.
[00:06:51] And that’s where I met Dr. Braunstein when he presented his trial. So I was interested in that from MSK. Dr. Braunstein is a really open person, open to all the discussions, and I was very interested in the concept of potentially curing, which that he’ll go into more about the trial, oligo-metastatic disease, because that, even though the ARCHER trial is for HER2-positive patients and my subtype is different, the concept is very pertinent to, to myself.
[00:07:28] So it was a, it was very easy transition for me, and Leon made it easy to… He’s very receptive to all of our ideas. All the patient advocates had ideas in the– when he presented to the group, and then we were able to continue a more personal conversation.
[00:07:45] Adam Walker: Oh, that’s fantastic. Now, Dr.
[00:07:46] Landsberger can you explain to us, like, what patient advocates do when they sit down with researchers who are developing the clinical trials like ARCHER? Like, what are you discussing aside from just the science?
[00:08:01] Dr. Ellen Landsberger: Well really the questions that I’m looking at is what’s the purpose of this trial?
[00:08:07] What are they trying to get– what is the researcher trying to get? What question is it are they trying to answer? Who is this being directed towards clinically? Like who’s going to benefit from this? What it… What kind of patient et cetera. And are they really addressing what patients want to know?
[00:08:29] Yeah. The questions are different, the answers are different, and the goals may be different. And as the research gets developed, as the protocol gets developed, you want to see better synergy between those two viewpoints, what the researcher wants to know and what the patient wants to know
[00:08:49] Adam Walker: Gotcha.
[00:08:50] And so I also know that a lot of people are leery of participating in clinical trials because they worry they’re going to get the placebo, or they worry about unwanted side effects from an experimental treatment. So how do you help researchers better understand the potential barriers like those that keep people from enrolling in the clinical trials?
[00:09:10] Dr. Ellen Landsberger: Well, the placebo issue is really a false issue. Okay. So more than dealing with the researchers, they deal with the patients about that. Because nobody wants a placebo. And in the cancer trials, we’ve learned that everybody gets treated, and sometimes it’s standard of care, and you’re adding the trial drug to the standard of care.
[00:09:34] Oh, okay. And so everybody’s getting treated. And people aren’t They, the patients think of themselves as being experimented on, and the idea is not to experiment on the patient. It’s the drug that’s being, that is the experiment. And so working with the patients, working with the researchers to see what the patient’s concerns are-
[00:09:58] Adam Walker: Right
[00:09:59] Dr. Ellen Landsberger: trying to align those. That’s how you can bring that together. But I think that’s a real misperception in, of that, th- that you get placebos.
[00:10:08] Adam Walker: So yeah, ju- just to reaffirm, reiterate that and make sure I understand it, so when you say they’re getting the placebo, what they’re really getting is what they would be getting not in the clinical trial anyway, right?
[00:10:19] Dr. Ellen Landsberger: Correct.
[00:10:20] Adam Walker: Okay. Okay. That’s-
[00:10:21] Dr. Ellen Landsberger: I mean, that, that’s one of the arms of it, yeah. There are different approaches to it.
[00:10:25] Adam Walker: Of course.
[00:10:27] Dr. Ellen Landsberger: Different trials do it different.
[00:10:28] Adam Walker: But generally speaking, that’s the case. Yeah. Okay.
[00:10:30] Dr. Ellen Landsberger: That’s- Everybody gets treatment.
[00:10:32] Adam Walker: That’s very helpful. That’s a very helpful lens to, to view that through.
[00:10:36] I appreciate that. Now now Dr. Landsberger o- one or two more questions for you here. E- have there been any specific, like, light bulb moments during the design process where like, one of the researchers said, “Wow we never thought of it that way,” and it actually affected or changed the trial protocol because of you?
[00:10:54] Dr. Ellen Landsberger: I was actually thinking about a trial that one of Dr. Braunstein’s colleagues was doing with using radiation and a drug that would sensitize increase sensitization.
[00:11:06] And one of the issues that many of us are very concerned about as treatment has changed is that no longer are we looking for the do we want to know the highest dose that we can tolerate, but what is the lowest effective dose of the drug- that we can have? Right. Lower dosing being hopefully having less side effects. And this particular researcher had not thought of that at all. So we talked about a different approach rather than just pushing up more and more drugs, more to studying the effectiveness at different- and that was really helpful. And he specifically said, “Gee, I never really thought of that.” So that, that was, that made me feel better.
[00:11:53] Adam Walker: That’s the magic line right there. I love that. Okay. That’s great. Now, Dr. Braunstein can you tell us a little bit more about the Archer trial? What are you hoping to accomplish through the study, and how do advocates help elevate its design?
[00:12:08] Dr. Lior Braunstein: Yeah fantastic. So Ellen actually alluded to a fair amount of this, but the study is essentially looking at patients with HER2-positive breast cancer, which is a specific subtype of breast cancer where we have excellent systemic therapy. And then for people generally speaking with breast cancer that has sort of spread beyond the breast or is metastatic the standard of care basically is systemic therapy today, and that means essentially drugs, chemotherapy or targeted drugs, and they’re continued indefinitely.
[00:12:38] And these therapies for HER2-positive breast cancer have become very effective. They’ve become actually very effective in a lot of breast cancer settings, but particularly so in this particular subtype of breast cancer. And people now live very well for years. But the framing for metastatic breast cancer, also known as stage four breast cancer, it’s always been about control rather than cure.
[00:12:58] So someone stays on treatment, hopefully for a very long time, but generally with the expectation that the disease is being managed sort of for a long period of time, but not quite eliminated. And so what the ARCHER trial is asking is if we can change the framing of that for a specific group of patients, and these are folks who present with HER2-positive breast cancer specifically, that spread only to a limited number of sites.
[00:13:23] And so Dr. Landsberger mentioned this. We call it oligometastatic disease. That has different definitions depending on the context, but here we talk about five sites or fewer. Oligo just means few essentially, so few metastases. And also, in addition to having spread to just a few sites, we allow people to start on their standard therapy, so people will start the usual treatment.
[00:13:49] Again, as Dr. Landsberger mentioned, no placebo. People start on what we know is effective as far as their chemotherapy and their targeted therapy for this type of breast cancer. And once we’ve identified that they’re responding well to that therapy in the initial few months, then they’re eligible for this trial.
[00:14:06] And what the trial’s effectively looking at is testing whether adding local treatment, meaning surgery and radiation, to all the sites of disease that we can see on top of the usual chemotherapy or targeted drugs, whether that can push us towards something closer to cure or at least towards sort of durable, more long-term control.
[00:14:27] And so everyone in the study re- receives excellent, standard, effective systemic therapy drugs. The question is whether adding, in addition to that, radiation and surgery changes the trajectory of the disease. Now, it’s important to know that, In earlier stage breast cancer, stages one, two, and three, the goal of treatment in those stages is actually to affect cure, to basically eradicate every last cancer cell.
[00:14:56] And in those situations, because the disease is considered to be confined to the breast and the lymph nodes, it’s still in the local area, we use radiation and surgery routinely to try to destroy every last cancer cell. In stage four disease, that paradigm’s a little bit different because radiation and surgery obviously only work where you target them, and in stage four disease, the thinking is that the whole body unfortunately is harboring little microscopic cells that you can’t see.
[00:15:24] But in this specific type of breast cancer the agents, the drugs, the chemotherapy, the targeted HER2 agents are so effective that it’s entirely possible that we’ve eradicated all the cancer cells that you can’t see, and that all that’s left is effectively what you can see. And so what led to this was that on some of these landmark studies of chemotherapy for this particular disease, we see that a small minority, but a measurable minority of patients, once they start the chemotherapy Their disease doesn’t really show up again as long as we follow them for up to a decade at this point.
[00:16:05] And so that kind of raises the notion, have you already been able to control everything, and now they’re just staying on the therapy because we don’t know whether it’s safe to stop? But there probably are people out there where we’re starting to think that maybe we have eradicated every last cancer cell, and the thinking is that adding surgery and radiation might be able to increase the proportion of patients where we’ve done that.
[00:16:24] And so the second part of the question was about advocates, and Dr. Landsberger and her colleagues in the patient advocacy sort of working group where we designed this study really influenced the fundamentals of this trial. They influenced what we chose to measure. So a trial like this typically just measures whether a cancer has come back or not and for how long.
[00:16:49] And that matters importantly, but of course, our advocates also insisted that those numbers don’t necessarily capture the entire experience in terms of what everyone’s interested in. And so this Archer trial specifically also measures quality of life. It measures patients’ anxiety over the treatments.
[00:17:05] It measures the degree to which thoughts about the illness intrude on work and relationships, and and people’s feelings about what they anticipate from this more aggressive treatment and how the treatment works, frankly. If we are more aggressive about our therapies, but our patients have a harder time going through treatment, that’s something worthwhile for us to know because quality of life is obviously very important in terms of the long-term outcomes that, that people care about.
[00:17:32] So there are a number of surveys that are part of this study as well, very interested in the patient experience on the study, and essentially incorporating the questions and the measurements that matter most to patients because ultimately, folks who choose to enroll in this kind of trial are going to be influenced very heavily in terms of their long-term outcome depending on what treatment they receive.
[00:17:57] Adam Walker: Okay. And I know that that the study was shaped with input from patient advocates from the outset addressing some of the questions that matter most deeply to them. Do you have any examples of some of the, what the, some of those questions are that you’re directly addressing?
[00:18:12] Dr. Lior Braunstein: Yeah. So e- exactly the side effects of the treatment, how people feel in terms of their long-term outlook. It’s very important there’s a literature that looks at what patients anticipate from a treatment versus what the doctor is trying to convey about the treatment. So there are a number of studies that look very specifically at interventions like this saying, “We think this will work, but it’s a hypothesis.
[00:18:38] We haven’t proven it yet.” And it’s very important for us to understand if patients are signing up for a trial like this expecting that it will cure them versus understanding the limitations of the scientific question, and understanding that there’s a probability that may happen, but we may turn out to be wrong, and it may actually not have that effect.
[00:18:56] So dissecting that very carefully and ensuring that expectations are aligned with where the science is absolutely critical.
[00:19:03] Adam Walker: Okay. Yeah. Yeah, I like that. Setting expectations is is absolutely critical, that’s for sure. Now, Let me interject something about that. Yeah. Go ahead. A number of studies look at these the patients, experience in this. They’re called PROs, patient-reported outcomes, and they’re surveys, and you answer a lot of questions and about side effects and anxiety, the things that Dr. Braunstein mentioned. They tend to get separated from the result, the scientific results of the trials. So the science is reported first, and the PROs are reported later on.
[00:19:42] Dr. Ellen Landsberger: And if you look at some of this, in the first paper, the doctors report on the outcomes and the patient’s side effects, and in the second paper, the patients are reporting on it, and they don’t always align. And so and that’s a commitment that we ask from all of our researchers, like, put these PROs out, do the results of this.
[00:20:03] If we’re going to spend the time answering these questions, we want to know the answers as much to those issues of quality of life that we’re going to experience in addition to the scientific aspect. Different people are going to have different different risk tolerance. We know that. So the more information that you can have about these treatments ups- upfront, the better it
[00:20:27] is.
[00:20:28] Adam Walker: I love that. Okay. Now, Dr. Braunstein clinical trials often struggle with diversity. How did your patient advocate push your team to think about geographic, financial, and racial equity when choosing the centers where the ARCHER study would take place?
[00:20:47] Dr. Lior Braunstein: Yeah that’s a real and challenging problem in a lot of oncology and a lot of medical research sort of writ large.
[00:20:54] And so for decades, really, the patients who ended up in our trials particularly at my institution, they kind of s- have skewed white, affluent, urban. These are kind of populations that are already at major academic centers or the surrounding geography, and it’s not because anyone designed it that way on purpose.
[00:21:12] It’s just because trials tend to open at the institutions where the investigators are already working, and those institutions serve particular populations. And so my institution happens to be on the Upper East Side of Manhattan. There are other institutions that have very different sort of nearby geographic populations.
[00:21:29] But if you’re not deliberate about it, you sort of reproduce the same inequities every time you open a study just by virtue of geography and location. So our advocates really pushed us to sort of reframe the question. So instead of asking where we could most easily open the trial, the question really became, where are patients sort of systematically underrepresented and kind of falling through the cracks when you ask these questions?
[00:21:51] So it’s a bit of a different question. It leads to opening the study at slightly different sites than maybe typically. Again, as I sort of alluded to, we’re running this ARCHER trial through the Translational Breast Cancer Research Consortium, which has a national footprint, and as we’re expanding, we’ve been quite intentional about including centers that have large, sort of diverse nearby underserved communities.
[00:22:15] We’ve also Incorporated some practical considerations in the study where folks can get the majority of their treatment quite close to home. They can continue on their systemic therapy locally with their local providers, and then basically just come to one of the large centers in an episodic fashion to get surgery and radiation, and then go back home, and we do the rest of the monitoring largely remotely.
[00:22:38] And so that also allows a much larger footprint of folks to participate. It alleviates the burden of of travel. That, I mean, that’s a huge economic burden on folks when they’re coming in routinely on an indefinite basis, and it also sort of democratizes access to the study so people can participate in this exciting research regardless of where they happen to be, so long as they can kind of get to us one time in an episodic fashion.
[00:23:04] Adam Walker: Oh, man. I love that. That’s great. I’m very… I’ve d- we’ve talked a lot about transportation problems on this show and how that can produce inequity, and so I love hearing that. Dr. Braunstein are patient advocates a standardized part of clinical trial design today, or are they becoming more common in the research community?
[00:23:25] Dr. Lior Braunstein: It sort of depends. It depends very much on where you look. I mean, directionally, I think patient advocates are getting much more involved than they have been historically. That’s absolutely true. Involvement has moved from when I was in training to a rarity to something that’s sort of increasingly expected as people are designing trials.
[00:23:44] And in some pockets, you actually find that it’s mandatory. So there are a lot of funders, including some federal funders, the Department of Defense has a breast cancer research program, now the Department of War has a breast cancer research program, and I think for some of their mechanisms, they actually require that scientists involve advocates or patients in their projects, and they even seat advocates on the panels that decide what research gets funded.
[00:24:08] So that’s a pretty fundamental manner in which the patient voice flows directly into the design of the studies. And that’s a meaningful shift because it actually puts the patient advocate voice before any money and decisions flow into any of these studies and that’s that’s about as early as you can get.
[00:24:26] But I wouldn’t declare victory just yet. I think there’s probably still plenty of studies that squeak through with very little by way of patient advocacy early on, and there’s probably still a great deal also of probably what you can think of as like ceremonial inclusion of an advocate where they’re added quite late just to, to sign off and give that semblance of input.
[00:24:52] So I think generally speaking, the field has probably won the argument that the advocates belong in the room and they’re requisite for the design of these studies, but the work goes on, and we have to make sure to keep spreading the word and ensuring that the science really considers the the patient perspective, the patient role really fundamental to the nature of how these studies are designed.
[00:25:14] Adam Walker: So I guess, Dr. Braunstein, with that in mind do you have a message to any cancer centers that, that might still be designing trials kind of in, in isolation without patient advocates at the table?
[00:25:27] Dr. Lior Braunstein: Yeah. It’s something we talk about routinely. And basically, I would say that designing a trial really without a patient advocate is just not the most rigorous way to do the science these days.
[00:25:36] It probably creates some blind spots and it makes the trials a little bit weaker. And so we’re trained to think that scientific objectivity means sorta keeping the personal experience at arm’s length from people’s concerns. But the critical thing is that a clinical trial is typically not just an experiment.
[00:25:57] It’s something that you’re asking for real human beings to live through, and a beautifully designed study, no matter how scientifically sound and beautiful If no one’s going to enroll in it and it’s measuring things that patients don’t really care about, it’s already failed before it’s gotten off the ground.
[00:26:11] So I’d encourage my colleagues, many of whom are already on the same page with me, to consider the fact that advocates make the science better. They don’t make it softer or fluffier. They actually truly make the hard, rigorous science much better.
[00:26:24] Adam Walker: I love that. Well, Dr. Landsberger my last question’s for you.
[00:26:28] I think patient advocates are amazing human beings. And I just, I so admire what you do. And so if someone’s listening today and wants to become a patient advocate how would they go about that?
[00:26:43] Dr. Ellen Landsberger: Well there’s a couple of ways. One, a first way is to ask their oncologist. So that’s how I started, how the path that I got my oncologist turned me on to the social worker, turned me on to some other people, et cetera.
[00:26:59] And there’s some organizations that I think are very helpful. There’s some courses. Komen g- has a course on advocates and science. There’s Project Leads, z- sponsored by the National Breast Cancer Coalition. These are programs that will teach the patients about the science so that they can discuss these projects with the researchers and feel less intimidated by it and more open to being able to share their their thoughts.
[00:27:29] And I thought about an organization called GRASP which aligns researchers with patient advocates- To work together, so something like GRASP that can help people meet each other and share the ideas. And then just to talk to other patients most of us who are involved in this would welcome we welcome other patients to get involved in this, because everybody brings their…
[00:27:57] we’re all experts in our own experience. Right. Right. Yeah. And it takes a little while for the patient to understand that and to jump over that hurdle and get involved. But once you get involved, it can be really very rewarding.
[00:28:11] Adam Walker: I love that. Well, d- Dr. Braunstein, Dr. Landsberger, I l- I love the work that you’re doing, so appreciate, this community appreciates the work that you’re doing, and thank you for taking the time out of your day to join us on the show today and share it with us.
[00:28:24] Dr. Lior Braunstein: Thanks for highlighting a very important topic. It was a pleasure.
[00:28:27] Dr. Ellen Landsberger: Same. Thanks for having us.
[00:28:29] Adam Walker: Thanks for listening to Real Pink, a weekly podcast by Susan G. Komen. For more episodes, visit realpink.komen.org, and for more on breast cancer, visit komen.org. Make sure to check out @SusanGKomen on social media. I’m your host, Adam.
[00:28:43] You can find me on Twitter @AJWalker, or on my blog, adamjwalker.com.