Educated Patient® Metastatic Breast Cancer Summit Updates in Disease Management Panel: June 11, 2022

This panel featured Dr. Suchita Pakkala, Dr. Jane Meisel, Dr. Keerthi Gogineni and Kelly Shanahan.

Meisel: I just wanted to ask Kelly, since you haven't had the chance to speak with us yet. Tell me a little bit about what you're most excited about. And we've seen a lot of new data here. You know, just thinking about what are the things that from your standpoint, excite you?

Shanahan: Unfortunately, I was not able to be at ASCO in person and was able to catch a bit of it virtually. But one of the things I think a lot of us, even those of us that don't have HER2 overexpression, are really excited about is the possibility of using TD XD and HER2-low disease. I mean, I'm sitting there going please, please develop some HER2 overexpression even if it's only one or two plus because I think that data deserve the standing ovation that it got. You know, it was always in the past that ER-positive disease was (the) subtype to have…over the last few years, (but) with the explosion of options for HER2-positive disease have been going when is it our turn? So at least now people with HER2-low disease have what looks to be an excellent option, not an option without its side effects and pretty significant side effects according to people I know that are on these drugs. But it does…give us hope. It's not a glimmer of hope. It really is, as I tweeted, it's a bright, shining star of hope for people with HER2-positive and HER2-low disease.

Meisel: Yeah, no, I completely agree. And a couple of things I would add on that. I mean, I think I agree with you. And being in that audience for the standing ovation, it did feel historic, and just the idea that we can offer this as an option to so many patients who previously didn't have this kind of option is fantastic. And I think also the science that allowed this drug to be developed where you've got HER2 as a target. But it also is able to get at these HER2-low patients, I think means that this will open the door for potentially more treatments like this. And actually, I had my first conversation with an insurance company yesterday to get this approved for HER2-low patient. And I was surprised at how amazing they were I had to get on the phone with someone. But he immediately said I saw your notes. I pulled up the New England Journal (of Medicine) paper and like, absolutely treat your patient today. So I do think that even before we get full FDA approval for this and the HER2-low patient population, we will be able to see this progress forward.

Shanahan: That's super exciting, from a patient standpoint, to hear that an insurer, who it is their first priority to actually maybe help us by saving money. It has authorized the use of it when it's not FDA approved for the HER2-low indication. That was you know, something that was a conversation among patients and even among oncologists, right after this was like, “Hey, I'm gonna start prescribing this on, you know, Monday or Wednesday.” But is insurance gonna pay you?

Meisel: I think one of the things that was great about that was that they did publish in the New England Journal of Medicine the same day. And so doing a journal paper in our, you know, pre-certification package for insurance that often does speak for itself. So I think, you know, hopefully many people will have the same good luck. Yeah. And we're in Georgia, I think there are other states where insurance may even be more up on the data than down here. So we'll see.

Pakkala: I thought for myself as we oftentimes can get patients therapies, where we have the data and we can argue for that data. So, you know, even if it's not approved, sometimes as long as we can say that this is going to benefit our patient, sometimes we can get it approved.

Meisel: Totally. So another great question for the audience. Couple that are filtering through now. Someone asked about treatment options for men with metastatic breast cancer. Dr. Gogineni do you want to maybe take a stab at that?

Gogineni: Sure. You know, generally speaking, most of the time when a male is just diagnosed with breast cancer, it's usually going to be hormonally driven. So we use many of the same drugs. The truth is that when you think about the trials that led up to the approval of those drugs, there weren't as many men in the trials. That doesn't mean that we can't use the drugs. We have to be a little bit careful when we're using drugs other than tamoxifen too. Also think about whether there's some estrogen production that requires us to also use some of those drugs that Dr. McCollum mentioned, like Lupron or Zoladex, which we use a lot in prostate cancer also. But in general, whether that breast cancer in a male is HER2-positive, estrogen-positive or triple-negative, we use the same armamentarium for these folks.

Meisel: Yeah, I think that's a great point. And I think I would add, there's also a lot of interesting stuff coming up now about real-world data, because we've got electronic medical records now that are often more integrated with data collection. And so we're getting more information about our male patients, and how these treatment options impact them. Through because there are not that many men enrolled in metastatic breast cancer trials. But exactly, you know, we really treat them much the same way based on receptor status and with a lot of shared decision making.

Shanahan: Wasn't there something that using real-world data, and potentially in future clinical trials, you know, instead of having a control arm, being able to use real world data in real world evidence as that control arm and therefore getting more people on the investigational new agent, which I think makes it more attractive from the patient's standpoint, to enter a trial.

Meisel: Yeah, no, I think that absolutely is true. And I think now that we have more robust ways of collecting real world data, that may even become a reality. So I think there will definitely be more to come on that. But I think as investigators and companies look to design more efficient trials that are more attractive to patients and, you know, attract a wider diversity of patients, stuff like that becomes really a lot more important. So, it's good that we have that capability now, which we really didn't have even like five years ago.

Let's see there are a couple of great questions filtering, and I want to make sure we have time to answer many of them. One question, I think, is a really good kind of question that spans all of these options is how much and what kind of progression on first-line treatment makes second-line treatment necessary? I think that's a great question. I'm happy to take a stab at that. But Dr. Pakkala, maybe let me let you speak to that. And then I can add anything that I have to add after that.

Pakkala: Yeah, so in a lot of the clinical trials, they use the number of 20%. But again, it really depends on what you're measuring. So you have to be consistent in what you're measuring or new sites of disease. So if you're having any, you know, new bone disease, or some new area that's showing up, then that defines progression. But sometimes, again, if a patient is slowly progressing, meaning we may see one new spot and not five minute spots, we may say, “Well, you know, we can just monitor this one new spot and continue on the therapy that you're tolerating well.” And then at what point that we feel that you are progressing more then we change your therapy.

Meisel: Yeah, I think that's great. I think sometimes it's obvious that a change in therapy is needed. A patient's feeling a lot worse, or they've got new liver metastases say, they never had liver involvement before. But a lot of times, especially it depends on the subtype. But a lot of times, if things are kind of percolating along slowly, you can have these discussions and I have several patients that have had very slowly progressive disease where they're tolerating a treatment well, but maybe there are a few lesions that have grown by, you know, 1 to 2 millimeters over three months. And I typically don't change treatment over that, you know, I think, for me, I sort of acknowledged to them that like the time may be coming, or we may have to make a change. But as long as your labs continue to look good, and you continue to feel well, I think we can safely wait until the next scan. So I think that's a great situation where I think now, because we have the ability to monitor people closely, and because we have a lot of good options from almost all of these subtypes. A lot of times you can, you don't have to make a huge switch at the sign of first potential progression.

Shanahan: And what about the idea of using something (other) than imaging-based markers? I know for people like me that have extensive but bone-only disease, you know, you couldn't tell whether a new something popped up on my bone scan. And it's difficult to measure. So what about the idea of using biomarker-based or circulating tumor DNA or circulating tumor cells as that marker of progression, maybe along with imaging, but you know, especially for those of us with extensive bone only disease, I think we need something above and beyond imaging.

Meisel: Yeah, no, I think that is definitely where the field is starting to go with so much research now actually in circulating tumor DNA, which is a little more specific than the tumor markers like CA2729 and CA153, which we can check into, which can be great markers for some patients. But I think especially with bone only where it's not as easily measurable on a scan, even a bone scan. That can be a very useful adjunct to kind of try to understand how people are doing.

Pakkala: In terms of DNA, there are several trials that are looking at the role of ctDNA. So we do know that sometimes with, you know, what ctDNA is, is basically a kind of tumor cells that may be found in the blood. But what we don't know is, you know, how do we integrate therapies or changes in therapies based on that right yet. But that's what the studies are looking at, like, how do we now decide how to use this information now that we have it?

Meisel: Another question that came through, we've got so I love all this involvement. We got so many great questions here. One, I will direct to Dr. Pakkala. This was comment on ESR1 mutations in hormone receptor-positive endocrine resistance.

Pakkala: Yeah, so ESR1 is usually in about 20% of patients. If it is detected, then sometimes we use the third, which are the receptor degradation of fulvestrant (injection), there are newer certs that are being looked at that class of drugs. And there are several clinical trials that are now ongoing, even at Emory, where hopefully, this may be another mechanism where we can use these drugs to overcome that kind of resistance.

Meisel: Yeah, there's so many great trials in this space. And I do think seeing antibody drug conjugates as one of the big stories of ASCO this year, I do think there could be a time where SERMs are, you know, become more of the theme…And I think, you know, solidifying that language will also be important, (because) I think it confuses a lot of people, doctors and patients. But I do think that's going to be a great space for drug development.

Kelly, one question that is directed towards you. There's sort of a theme and a few questions here is wanting to learn more about that patient and health care team partnership and the importance there. And we've talked a lot about shared decision-making and treatment options. Give us some of your wisdom on this topic?

Shanahan: Well, you know, there needs to be a partnership between bench researchers and clinical researchers/oncologists and the patient. The bench researchers are experts in the whys and wherefores of cancer, you oncologists are experts in treating cancer. But us patients were people living with disease, we are the experts in living with metastatic breast cancer. And I think not only in terms of research, but also in terms of our individual care that when we partner with our care team, we get much better results. And the first time a patient asks a question like, “Doc, why are you recommending this treatment? What are the side effects going to be from this treatment? Doc, you didn't tell me about this. This is what I'm experiencing.” You're becoming an advocate, you're an advocate for yourself.

And I think we all learn from each other. And you know, we truly are stronger and smarter together, when we partner in a meaningful way. In every aspect of cancer care, from the earliest stages of research, all the way through you being the patient sitting in your doctor's office discussing progression and your next options for treatment, including clinical trials, which unfortunately I don't think are discussed early enough, and often enough, and I think there is this misperception on the patient community that clinical trials are a last resort. And I think some of that comes from some of our oncologists, and even some oncologists at major academic centers, not just community oncologists, that, “Oh, we've got all these things. Let's wait for a clinical trial.” And I think as patients, we have to be proactive. We know ourselves best. We are our own best advocates. And we also need to find care partners who respect us and want to work with us. We all deserve that.

Meisel: Yeah, no, I think that's very wise information, I do think is, as physicians, we can learn so much from our patients, both in terms of, you know, how we think about clinical trials and how we discuss them, because you're right, I mean, we have trials, as you've seen, all of you have seen that, you know, really have impacted how we treat first-line and second-line (disease), like it's definitely not just a last resort thing. But I do think sometimes when they get brought up later, there's that perception of oh my god, she has nothing else to give me. I think for all of us, it helps to really put ourselves in our patients’ shoes, to think like, if that were me, like what would I want to hear? What would I need to hear? And how would I tell this to myself.

Shanahan: And clinical trials are not necessarily the be-all and end-all, especially in terms of side effects. I think a good example of something you mentioned earlier when you were talking about (Perjeta [pertuzumab]). And the side effect profile in the original clinical trials, itching was not reported. And when he was on Perjeta I started reporting it, it was like, yeah, It's on the list from the trials, because it's a late side effect after the trials, and it was patients talking to their oncologist about the itching that they're experiencing, that led to it being a recognized side effect. And it can be debilitating. I've had friends on Perjeta who had such poor quality of life because of the itching that after, you know, periods of stability, have elected to go off of it. And I think as patients, it is incumbent upon us, and I know I am guilty of this, I minimize telling my doctors about my side effects if I'm on an otherwise effective treatment, because I don't want to change. And I think it is incumbent upon us as patients to be upfront and honest with our doctors about what we are experiencing and let them know everything because again, everything's not apparent in the timeframe of a clinical trial.

Meisel: Yeah, everything's not always apparent in the clinic visit. But I do think a lot of it, and I've had patients tell me explicitly that like, they tried to put themselves together for their visits or family members tell me like she made it seem like she's doing really well. But like, here's what's happening. And I do think sometimes that is, like you said, out of fear that like what if the doctor wants to change the treatment or stop the treatment? But I think there's agency in that too. And I've definitely had conversations where I say, you know, it sounds like you're really struggling? Like, are you sure you want the full dose? Are you sure you want to continue? Here's the other option. But I definitely think patients also have agency and I've had people say, Yes, I do. And I'm so glad you brought that up. But I've also had people say like, continuing this treatment is more important to me, it's working, give me the full dose. And I think it because there is a lot of potential right paths, we have to be able to listen to our patients but I think our patients have to be able to trust that they can have that conversation and be heard.

So much to talk about here. Another question. I think this is an interesting one. And I think probably worth raising. Someone said please address the disappointing palbo data in metastatic breast cancer. Dr. Gogineni, do you want to tell us what that data was and kind of give a summary and then we can talk about how we feel about it.

Gogineni: So it's been challenging for us, as providers to kind of distinguish between the different CDK inhibitors. So we've got three that are on the market. (Ibrance [palbociclib]), (Kisqali [ribociclib]) and (Verzenio [abemaciclib]). And they haven't been compared head-to-head to each other. But each of them has been coming out with different sets of results over the years. And we've seen some signs of what we call overall survival improvements with certain of these drugs, including Kisqali. But the palbociclib data that were presented at ASCO last week. We didn't quite hit the mark on that. And so if one is starting a CDK inhibitor now, and you're kind of questioning “Well, which one do I start first?” Some of this may come down to potential side effect profiles. And as Dr. Bacala had mentioned, there's a few that have more of an impact on your white blood count. But that might not necessarily translate into effect on the fever infection. Whereas the present can have an effect on diarrhea. Kisqali requires a little bit more monitoring with EKGs. But I think that right now, if we had a woman who was starting this drug, and they were either pre-menopausal or postmenopausal would be leaning towards thinking about the ribociclib or Kisqali. Because of this data that we've been seeing now, in the past few conferences.

Shanahan: Do you think consensus is that if you have someone who is on palbo? Well, that you would not change them at this point. And also, I haven't been able to delve into the trial and the data in detail. But you know that one of the questions that came up in my mind is, you know, did they check for ESR1 mutations? Was there a higher incidence of ESR1 mutations? Because the patients were on either palbo plus letrozole or letrozole alone. So you know, if in that group that was on palbo, there was a higher incidence of ESR1 mutations, well, then maybe it's not the palbo maybe it's you know, the fact that letrozole is ineffective, or any AI is ineffective in the face of an ESR1 mutation. So you know, I think there's still some questions to be answered. And, you know, as a patient, I'm sure you guys as oncologists, you know, would love to see some head-to-head comparisons because, you know, until you have those head-to-head comparisons, it's conjecture. Yeah, I think populations can be so different in these trials. How many lines of prior lines of therapy were in Paloma? How many prior lines of therapy and Monalisa you know how many in all these different trials the patient characteristics can be very, very different.

Gogineni: That's a really good point. I think that in this Paloma-2 trial, what you've said earlier, if someone's doing well on Ibrance or palbociclib, or whatever it might be, I would not switch them, I think all of us would keep them going on the same course of treatment that they're on. The women that were on the Paloma-2 trial were on palbociclib and letrozole. And to your point, no drugs like that can create an ESR1 mutation over time. And did that affect something? I don't think they actually reported on that at this abstract. But it's a really good question.

Meisel: Yeah, and I think a lot of that biomarker data will be forthcoming, and also some real world data, because I think they do have a lot of real world data analysis. Palbociclib has been on the market since 2015. And I think a lot of people also have made the point, which I think is a good one, that our clinical trial populations don't always fully reflect the real-world patient population, you know, they can be a little like ivory tower, so to speak. So understanding that real world data will help too. And I think you have a sense of is a great drug if you woulda came to market first. And it really revolutionized how we take care of these patients. And as they reported, you know, a good 10% of patients on that trial are still on the problem that result seven and a half years. And definitely patients in my clinic who've been on that combination for years, and they've done really well. So it's certainly not a bad drug, I think it's just a little hard to reconcile, like survival data, and the other two without survival data for this. But I do think there's still some things to be looked at. And it's certainly not a foregone conclusion that you wouldn't start this drug again, you know, I think, also there are slightly differential side effect profiles with the three drugs and so there may be people, you know, for whom, like rabbits, like we have to check in kgs more frequently and abemaciclib causes more diarrhea, were maybe probably would be the right choice, again, because those quality of life concerns. So I think there's, you know, probably, my guess is that what will happen is that it will have less of like the lion's share of the market, because of this data, but it will still remain a very viable option.

Shanahan: Because we have like 80% of the market or something ridiculous. And I know, last year when I had my first progression, and we were adding a CDK4/6 inhibitor, and in discussing it with my brilliant mBC expert oncologist, who was privy to, you know, some of the preliminary data, and was kind of steering me towards abemaciclib. And I'm like, there are two side effects that I despise, and that, you know, vomiting, and diarrhea. Yeah, I was about to do a road trip with my daughter. And I'm like, I cannot start a drug with a high incidence of diarrhea. And so we had a negotiation, because, again, she was privy to some of this data early. And, you know, I chose to go on the palbociclib, you know, knowing that ribo could be used in the future. And then the clinical trials that, you know, might be available for someone like me, it's relatively heavily pretreated in the future.

Meisel: Yeah, no, I think that's like a perfect example of the sort of like, gentle push back that is really required, because we do see a lot of data and we are incorporating that into our practices and all that stuff. But I think people stop to different degrees to think about, like, what is this person's priorities? Like, what road trip? Did they have planned? Like? What are they doing professionally? How is the side effect and impact them? And how much do they care about it? So I think, understanding what the side effects of a drug are, and what are the alternatives is so key, you're obviously the epitome of the educated patient, you know, but I think it is, these are really important life lessons for doctors and for patients about, you know, how to really conduct those conversations, because I think each progression is emotional. And it does involve a lot of thought.

Shanahan: And and I think that's, you know, very important to, you know, to ask the patients and for patients to let ER doctors know, you know, what is what will we put up with? And yeah, changes when I was first diagnosed with metastatic disease. My daughter was a sophomore in high school and not, you know, not quite 15 years old. I would have taught if they told me my right arm was going to fall off, but I would live to see her graduate from high school, I would have done it. Yeah, now graduated from college, she is kinda sort of making her way in the world on her own. And my priorities have changed quality of life is much more important to me now than it was when I was still raising this young woman. And, and I think sometimes, both his patients and I think as clinicians, it's, you know, it's what was told at the beginning, and we don't update that and I think it's really important for for you guys as oncologist to say, what are you know, what are your goals of therapy now? And for us as patients to do the same thing, you know, my priorities have changed. I won't tolerate horrible side effects anymore. Um, quality of life is more important, or, you know, my kid is graduating from, you know, college, kindergarten, high school, whatever, I'm getting married, whatever in, you know, six months, and I will do anything to be there in six months.

Meisel: Yeah, yeah, no, I think having a good understanding of those priorities is really key. Because then we can help people and meet their goals, whatever those goals are. And as you said, those goals can change.

Transcription edited for clarity.

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