[00:00:00] Adam Walker: This episode of The Real Pink Podcast is brought to you by Relay Therapeutics. Relay Therapeutics is a precision medicine company based in Cambridge, Massachusetts that is transforming the process of discovering new medicines by combining leading edge computational and experimental approaches. Relay Therapeutics work in breast cancer focuses on the most frequently altered gene in metastatic patients, PIK3CA.
You can learn more at RelayTX. com
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.
Breast cancer treatment today is becoming more personalized, more precise. Precision medicine is rapidly expanding the options patients have for treating their cancer while helping them maintain a desired quality of life. An uncommon mutation in breast cancer called PIK3CA affects more than one in three people with breast cancer, making it harder to treat.
This mutation often leads to worse outcomes for these patients compared to others. Scientists are now developing new treatments that target this mutation specifically, aiming to reduce side effects and improve treatment outcomes, such as shrinking tumors or preventing disease progression. Today, we’re speaking with Dr. Sarah Sammons of Dana-Farber Cancer Institute to explore the exciting new possibilities brought by personalized medicine, including whether it can help slow disease progression and how it can improve patients abilities to potentially live more active and productive lives while on treatment. Dr. Sammons, welcome to the show.
[00:01:45] Dr Sarah Sammons: Thank you, Adam. I’m happy to be here.
[00:01:48] Adam Walker: Well, I’m glad to have you this is really interesting and I’m glad we’re talking about it, because I don’t know anything about it. So I expect I will at the end of this episode so what does personalized medicine mean to patients now as a part of their treatment?
[00:02:03] Dr Sarah Sammons: It’s a really good question essentially. The broad term of personalized medicine means trying to match a specific therapy to a specific patient and their breast cancer based on the genomic profile of their tumor. And we’ve actually been using personalized medicine for decades in breast cancer in some ways, meaning that we’ve always been looking at the tumor to see if it was estrogen positive or HER2 positive or negative for all of them.
But now within those subtypes, so within metastatic estrogen receptor positive HER2 negative breast cancer, we’re now even personalizing further by looking at dozens of different types of mutations and trying to match therapies. to the specific mutation that we can find in their cancer.
[00:02:57] Adam Walker: Okay. And so it’s important for patients to know what kind of disease, what their specific mutation is then, correct?
[00:03:05] Dr Sarah Sammons: Exactly. And it’s important that patients know, that mutational profiling exists so that they can advocate to their providers, their physicians and make sure that this type of mutational testing is being done. Because it is standard of care at this point.
[00:03:25] Adam Walker: Love that. So let’s talk about the REDISCOVER trial.
So what is the REDISCOVER trial aiming to accomplish through personalized medicine?
[00:03:33] Dr Sarah Sammons: Yeah, so the REDISCOVER trial is a platform looking at a new therapy called Relay 2608. Which is, to me, exciting because it is a drug that specifically targets the mutation PIK3CA that is found in about 40 percent of patients with metastatic estrogen receptor positive HER2 negative breast cancer.
Now we have some drugs that are already approved in this space. We have alpelicib that’s approved for PIK3CA mutations, capibacertib, and now inovolacib. So we actually have options already for these patients. The Relay platform and Relay 2608 and some other compounds that are coming down the pipeline are exciting because they specifically target the mutation and they have the promise of hopefully sparing the normal cells that also have PIK3CA in them.
And so in doing that, the hope is that the side effect profile will be better for patients because The drugs that are approved have some efficacy, but they definitely have some challenges with side effects for patients. And so the hope is that the more specific we can be, the more we can actually target the mutation and not the normal cells.
The less side effects that will cause patients, and the better that will do in treating their cancer.
[00:05:01] Adam Walker: I love that. All right. Less side effects and less side effects means they can potentially stay in treatment for longer, right?
[00:05:07] Dr Sarah Sammons: It means that potentially they can stay on for longer. We also look at what we call discontinuation rates.
So how often does the patient have to stop the therapy? Not because their cancer is getting worse, but because they can’t tolerate the side effects. You can’t benefit from a drug that you can’t take, right? And so not only do we need to be working on more effective drugs, we need to be working on drugs with less side effects.
And I, do think that’s the hope of the Rediscover platform, Relay 2608, and other mutant specific, inhibitors that are out there.
[00:05:38] Adam Walker: Love that. Love that. We talk a lot about self advocacy at the time of diagnosis, but it’s important to advocate for yourself and for your quality of life.
Throughout your breast cancer experience, a huge goal of self advocacy is to work with your provider to minimize treatment side effects and improve someone’s quality of life while on treatment. So how can the patient perspective help to shape clinical trials with the goal of maximizing effectiveness and quality of life?
[00:06:07] Dr Sarah Sammons: It’s a really good question and it’s a metastatic breast cancer. So let’s take a step back for a minute and just talk about how we currently treat metastatic breast cancer. Currently metastatic breast cancer is not thought to be curable. Our goals are, our goal would be cure, but, in the absence of that, our goals are to offer treatments that prolong the amount of time until the cancer gets worse, so control the disease, shrink the disease, prevent it from getting worse for as long as possible.
We start the best therapy that we know of based on, large randomized clinical trials. And then we follow with imaging and lab testing and clinical visits the patients. And then at the time that the cancer is getting worse, then we switch to something else. And in doing that, many patients can live for years and years with optimal therapies.
But, our goal is twofold. It’s to prolong the amount of time to control the cancer from growing for as long as possible. And in doing that, if we can control the cancer from growing and spreading, then we would hope that ultimately we’d
also be prolonging their life. But then the second goal is to also make sure that the treatments are not dramatically impacting their quality of life.
What’s the point of prolonging someone’s life six, 12 months, 24 months if they’re feeling horrible while they’re on those therapies. And so we’re always balancing trying to get better therapies, but also trying to manage the side effects of those therapies so that patients can not only live longer, but they can live well.
And so how can patients advocate for themselves? Well, their doctors are going to talk to them about what’s the best therapy, what’s the best personalized therapy for them at the time of, they’re either new diagnosis or the time of their progression, you’re going to ask why are you recommending this regimen for me?
Has it improved? The amount of time until cancer progress has it improved the amount of time that patients lived And then by how much and if so, what are the side effects and so those are the questions that patients need to be asking. And then I would also take it a step further and say, are there any medicines that could potentially reduce the side effects that I might have. For example, capivasertib is approved for patients that have alterations in PIK3CA or P10. So as Alpella said, we know that if we give those patients antihistamines or Zyrtec, we dramatically lower the rate of rash that they might have. Make sure that they’re having a prescription for Imodium at home.
And the first, sign of diarrhea that they’re taking that so that it doesn’t get worse. For some medications, some of these medications, can actually cause high blood sugar. And so should I be doing a low carbohydrate diet? How are we going to be monitoring my sugar? Things like that.
And then also you can advocate yourself while you’re on the therapy because you don’t want to let, you want to let your team know when you’re having side effects. You don’t want to wait until the side effects are intolerable. You want to tell your team so that they can help support you through it before things get so bad that we have to stop the medication.
And oftentimes dose reduction, so reducing the dose of the therapy can be helpful. Oftentimes we have many supportive, medications or tricks of the trade that we can offer patients so that they can stay on the drug.
[00:09:55] Adam Walker: I love that. So let’s talk about clinical trials for a minute. Why is it so important for clinical trials to be a part of a patient’s standard of care and not a last resort?
[00:10:05] Dr Sarah Sammons: Yeah, I think that’s a really common misconception and that’s it’s also what I see in the clinic. So I’m the associate director of metastatic breast cancer, Dana-Farber, and I do clinical trials half the time. And oftentimes patients will come looking for a clinical trial for their, fifth, sixth, seventh line of therapy.
And that’s really not, sometimes we have trials at that point, but we have trials in the first line setting, the trials in the second line setting, we have trials in all of the settings. because every single new drug, every better drug that’s come along has come through in a clinical trial, right?
And the place that it’s studied is the place that the FDA approves it. And so we’re trying to do better. And all the different subtypes of breast cancer, the first line of therapy is being challenged right now. And so the next best first line trial is currently the next best first line drug is currently in trials right now.
And so you could potentially have access to that sooner. And we’re certainly screening our patients, in academic centers for trials in all settings, but that’s not necessarily always the case, in the community or things like that. But we do need to be thinking about trials, thinking about doing better than we’re already doing, until we have a cure. So because we always want to be doing better than first line, then second line, then third line, there’s always going to be trials in those spaces. for us trying to do better, and we can’t do better unless patients get involved in clinical trials.
[00:11:40] Adam Walker: That’s right. Yeah. So I’m just curious, how would you recommend a patient look at a clinical trial? Because, what you just said is interesting. I think you phrased it in a way that I’ve never heard a phrase where you’re basically saying, in some cases, you’re getting early access to a more effective treatment.
Is that kind of your viewpoint for a clinical trial? It’s a positive opportunity?
[00:12:03] Dr Sarah Sammons: Absolutely. Especially, phase two and phase three trials. There’s already some signal that this drug is exciting, that this drug is probably, working to some degree. But the time you get to a phase three trial, there’s been some pretty good signal that the drug may be better than the standard of care for the company to put.
Many, millions to potentially billions into that trial. And that’s one, one thing that’s challenging for patients is that, well, how do I know that the drug is going to be better than the standard of care? Well, we don’t.
That’s the whole point of the trial. But, especially if the there’s usually two arms to a trial, sometimes there’s three worst case scenario on a trial that has a control arm.
The control arm should be standard of care.
[00:12:54] Adam Walker: Right, what you’d be getting anyway, without the trial.
[00:12:56] Dr Sarah Sammons: What you would be getting without the trial anyway. So that’s what you want to be asking your doctor. What’s the control arm in case I don’t get the new drug that might be better. What’s the other arm that I would be randomized to and usually that’s what your doctor would be prescribing you a standard of care anyway, right?
And it can be a good opportunity patients on trials are monitored a little bit more closely Their. Scans are usually a little bit sooner sometimes the drug is given for free, sometimes it’s not. So lots of questions to ask the trial team, but, would say that we’re always trying to do better.
We’re trying to do better in the first line setting, in the second line setting, let’s talk about the first line setting for metastatic hormone receptor positive disease for the average patient. The regimen is going to work around, 22 to 24 months. Well, I want a regimen that’s going to work for five years.
We’re never going to get that unless we challenge it.
[00:13:52] Adam Walker: Yeah, that’s right.
[00:13:53] Dr Sarah Sammons: So that’s why we do trials in every setting.
[00:13:56] Adam Walker: I love that. I love that. So how can we ensure that, that all patients are educated about clinical trials and have access to clinical trials, especially black and Latina patients that are underrepresented?
[00:14:07] Dr Sarah Sammons: Yeah. Well, I would say that we’re definitely making progress there. Clinical trials used to be, thought about only in academic medical centers. That’s not really the case anymore. Clinical trials are in the community now. Clinical trials are at many, community sites. I would say, one of the main barriers is, just patients being offered clinical trials by their team.
And so one thing that you can do is say, okay, I hear you about the standard of care, do you think that there is a clinical trial that might be helpful or is promising that I could be involved in?
And if you’re at an institution that doesn’t have clinical trials, It’s not a bad idea to, get a second opinion, either a larger community practice or an academic center that does have access to many clinical trials.
And what we do, what I do is I often see patients who are treated in the community. Because it’s hard for them to travel to Boston once nobody wants to go to cities anymore, if they don’t live in the city, right? So they’ll come, they’ll come see me every couple of months.
They’ll check in send me a message I need a new treatment. Do you have any trials that would be interesting and then they can come see me but if you’re at, a more rural place or a very, community focused place that doesn’t have trials, it might be a good idea to get a second opinion of either an academic institution or a larger community institution that does have a clinical trial portfolio.
[00:15:42] Adam Walker: That’s good. Good advice. Good advice. So let’s go back, for a minute just to talk about the specific mutations, right? As the treatment landscape is changing, it’s hard to stay in the forefront of all that. Why is it important for patients, especially those from African American and Latino backgrounds to know whether they have a specific mutation?
[00:16:06] Dr Sarah Sammons: Well, we want to know the mutation. This is particularly relevant, Adam in hormone receptor positive for two negative breast cancer, metastatic breast cancer, and It’s important to know the metastatic, the mutational profile in metastatic breast cancer. We’re not currently testing that in early stage breast cancer.
So I want to make that clear.
[00:16:28] Adam Walker: Got it.
[00:16:28] Dr Sarah Sammons: The reason why the mutational profile in metastatic estrogen receptor or hormone receptor positive HER2 negative disease is so important is because we have great therapies that can target them. So we currently have therapies that can target ESR1 mutations. It can target PIK3CA, AKT, P10.
It’s important to know if you’re a BRCA2 carrier because we have therapies that could target that. It is important to know something called your tumor mutational burden, because if you have a very high tumor mutational burden, you actually might qualify for immunotherapy.
[00:17:07] Adam Walker: I wonder also about biomarker testing.
So is biomarker testing widely available? Tell me more about that option.
[00:17:17] Dr Sarah Sammons: So biomarker testing and mutational testing are similar, but not fully the same. Biomarker is any, it could be a mutation, it could be a protein, it could be anything that is going to tell us that you might that your cancer might respond better to a therapy.
So that’s what a biomarker is broadly. Now within biomarkers, there’s immunohistochemistry. So immunohistochemistry is what’s going to tell us. Are you still estrogen positive? Are you HER two positive? Are you what’s called her two low, which is a new biomarker, which could tell us if you are a candidate for a drug called Trastuzumab Deruxtecan, and even now soon, are you HER two ultra low, which is basically that, does your T have any expression of HER two at all?
And if it does, then you would qualify for a drug called INHER two or Trastuzumab Deruxtecan. So there’s immunohistochemistry biomarkers, and then there’s mutational biomarkers. Those are the PIK3CA, the P10AKT, ESR1, tumor mutational burden, sort of part of genomic profiling. And so I would say that mutational testing and immunohistochemistry are the main very important biomarkers
in metastatic breast cancer, that patients should make sure that they’re being tested for.
[00:18:46] Adam Walker: Okay. So, when I think of cancer treatment, I immediately think of IV medication, like that’s where my brain goes. While many people think of IV medications as their main cancer treatment in precision medicine, oral medications are becoming more available for many with breast cancer.
How can the advent of oral medications help improve access or outcomes for those with breast cancer?
[00:19:13] Dr Sarah Sammons: Yes. So I think oral medications are definitely more common in metastatic hormone receptor positive for two negative breast cancer. The first for the vast majority of patients with metastatic hormone
receptor positive for to negative breast cancer we’re going to be targeting estrogen.
So we’re going to be using endocrine therapies for most patients in the first and second line setting. Endocrine therapies target the estrogen receptor in a certain way and then they usually go with a second targeted therapy that which help that endocrine therapy work better, either a CDK four six inhibitor or a P3CA inhibitor, or an a KT inhibitor.
Now, most endocrine therapies are oral, most targeted therapies that go with endocrine therapies are oral. And so this is nice for patients because you, it is a drug that you take it home. You do not have to come to the clinic and have it administered IV and sit in the chemo infusion chair and, go with all of the things that feels like being a cancer patient.
It’s you’re taking a pill at home now; usually in the first parts of metastatic disease, this can mean that you’re only having to go to the doctor maybe every four to six weeks. Sometimes if things are stable, maybe even every three months. and so that’s certainly very helpful for patients with metastatic breast cancer because yes, they’re facing this diagnosis, but they also have lives.
They have families, they have jobs, they have other things, that they want to be doing instead of coming to the clinic. And maximizing oral therapy is nice because it can cut down on what we call time toxicity, which is the amount of time that you are physically going to the doctor, going to the lab, sitting in the infusion chair.
it can cut down on that a little bit. Now, one common misconception with oral medications, versus IV is that They’re always, going to have maybe no side effects or limited side effects. The oral therapies that we give do still have side effects. And so our teams, patients do still need to be seen they still need to be aware of you know the possible side effects with all of these therapies so that we can help them manage them
[00:21:47] Adam Walker: Yeah, I love that. And for people that don’t want to travel into boston all the time it’s probably helpful for them too, right? So yeah, exactly all right, so last question and I want to go back to clinical trials for just a moment. What are three questions you recommend patients ask their providers if they’re interested in learning more about clinical trials?
[00:22:08] Dr Sarah Sammons: Yeah, so I think anytime you have a new diagnosis of metastatic breast cancer or your disease is progressing or getting worse and you are being told that you need a new treatment, that is the time to
ask. Is there a clinical trial that might be promising for me? And so I think it’s important to know a few things.
First, what is the standard of care? Next best option that you would recommend for me and why it’s usually going to be based on clinical trials and that it was shown to be better than the prior therapy, right?
And are there any clinical trials out there that are close to me that are trying to do better than this
that, I might be eligible for. And then I think, there’s also, there’s early phase clinical trials too. So the different phases of trials are phase three is, it looks promising. We are challenging the standard of care. It’s the net, it’s the last step before it gets approved by the FDA and it’s available to everyone.
Phase two is usually that we’ve seen it work a little bit in phase one and we’re trying to learn more about it. But then phase one trials can still be very, helpful as well. Because every single new drug has to go through the phase one process first, which is where we first study it. We first learn about its efficacy.
We first learn about its safety. And those trials can also be, highly accessible and usually there’s no control arm there. So you’re guaranteed to get the drug. And so I guess anytime there’s a treatment change, is there a clinical trial that might be available to me? What’s the standard of care?
And if you are enrolling in a clinical trial, it’s obviously very important to understand What’s the new drug that I might get and what’s the old regimen that I might get? And what are the risks and benefits to both?
[00:24:06] Adam Walker: Oh, that’s great advice. Dr. Sammons, this has been enlightening. It is exciting medicine. I really appreciate you taking the time to join us on the show today.
[00:24:16] Dr Sarah Sammons: Thank you so much for having me. Happy to come back anytime.
[00:24:19] Adam Walker: Oh, I’ll hold you to that. As we heard from Dr. Sammons, quality of life is as important as disease progression for people with metastatic breast cancer.
For people looking for ways to prevent their disease from getting worse over time, with few side effects, personalized medicine may offer compelling new options. Thank you to Relay Therapeutics for supporting the RealPink Podcast.
Relay Therapeutics is transforming the process of discovering new medicines. By combining leading edge computational and experimental approaches. For more information about Relay Therapeutics, visit RelayTX.com.
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. You can find me on Twitter @AJWalker, or on my blog, AdamJWalker.com.