The Latest in Breast Cancer Clinical Trials

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today I'm happy to be joined by Dr. Jame Abraham, Chair of the Department of Hematology and Medical Oncology at the Cleveland Clinic Cancer Center, to talk about breast cancer trials. Welcome, Jame.

Jame Abraham, MD: Thank you, Dale. Thank you for having me.

Dale Shepard, MD, PhD: Absolutely. So you've actually been in your new role as the chair for... It's coming up on a year or so. How's the transition been from director of the breast cancer oncology program to chair?

Jame Abraham, MD: It's going really well. As you can imagine, when I took the job in August I was not expecting the world is going to change, and I am six months. So as you can imagine, we are dealing with all this COVID-19 crisis, but I think overall things are going really, really well. We have an outstanding team. We have an outstanding team. It's really stepped up to make sure that our patients and our caregivers are safe and are able to deal with this crisis.

Dale Shepard, MD, PhD: Yeah. What have you enjoyed most?

Jame Abraham, MD: Talking to people like you.

Dale Shepard, MD, PhD: Flattery will get you far.

Jame Abraham, MD: We have a great team. The docs are really good. They are, if I can say, really top notch colleagues. I really enjoy working with our colleagues. We have a really outstanding team.

Dale Shepard, MD, PhD: Can't agree more. I guess today we're going to talk about breast cancer trials. Maybe you could tell us a little bit about some of the key trials that we have ongoing at Cleveland Clinic.

Jame Abraham, MD: Our goal is to make sure that we have a trial for all subset of patients starting from early stage, from adjuvant setting to metastatic. Then when you come to metastatic in breast cancer, we look at ER-positive, or HER2-positive, or triple negative. Our goal is to make sure that all these subset of patients have a trial option. Then, as you know, unfortunately even now with all these advances happening in breast cancer, we still lose a number of patients because of advanced or metastatic breast cancer. So the goal is to make sure that we have a new trial option for any patient who is walking through the door.

Dale Shepard, MD, PhD: How do you line up the trials in terms of selection? If I'm not mistaken, you talk about these at tumor boards, for instance, and try to match up new patients to trials?

Jame Abraham, MD: Right, so multiple ways. One, when we have a new patient coming, one of the first questions we ask is do we have a trial? So our research nurse, I send a message to our research nurses, and we ask them to screen them for a trial, or sometimes our research team actually proactively screen those patients. That's fine, and of course we continue to educate our other colleagues to tumor boards. Then let's just say, like I'm sure like you, when I get a second opinion or a phone call from one of the doctors around the state or around the country, we always look for a trial and say, "Oh, by the way, we have this trial." Then the patient may end up coming here for a trial option.

Dale Shepard, MD, PhD: So you mentioned COVID, and all the associated issues with COVID certainly have wreaked havoc on many, many areas of cancer care. How about breast cancer trials? Have we still seen a lot of patients willing to come in for trials? What does that look like?

Jame Abraham, MD: So let's just say April or May, that time we were adjusting to this new reality. Now that this is June or July, now we know that we are going to live with this. So I think now if I can say okay, the trial team, and the doctors, and the nurses, we know that COVID is going to be with us for a long time, and of course the patients. So the patients know... or I guess we know how to navigate this environment now. So we continue to accrue patients for trial. We're not putting any trials on hold, so things are going well in that regard.

Dale Shepard, MD, PhD: Has there been anything particular you've had to change in terms of logistics to keep your trials going?

Jame Abraham, MD: So if you look at CTEP, NCI CTEP had some concerns about how often patients should be coming, and let's just say there is a blood draw which can be done at a local hospital, or let's just say this is looking at survival only, or some toxicity check, can we do that over the phone? So I think NCI, CITA, pharma companies, investigators are trying to adjust to this new reality by cutting down frequent visits, cutting down some blood draws, which can be done locally. Another really interesting thing, which NCI CTEP is talking about, placebo controlled trial that there's an IV placebo, and the patient is supposed to come only for that IV placebo to the hospital. That's the control arm, and NCI is actually in one of the trials which we are working through NRG oncology, and so I kind of said that we shouldn't be doing that now in this COVID time. So the overall goal is to cut down the exposure and making sure our patients are safe in this time by limiting travel, limiting exposure to the hospital site.

Dale Shepard, MD, PhD: I'm hoping that some of those changes, like letting people get local labs and things, will continue because it has significantly reduced the burden on patients.

Jame Abraham, MD: You're absolutely right, and allowing distance health, and allowing research nurses to reach out to the patients over the phone. I'm thinking many of these things are probably good, and this will, if I can say, bring some fundamental changes in how we take care of our patients.

Dale Shepard, MD, PhD: If you look at the breast cancer trials that we currently have open, are there any that you think have the greatest likelihood to make a big impact in how we treat patients with breast cancer?

Jame Abraham, MD: One of the really exciting compounds is DS-8201, or it's known as trastuzumab deruxtecan. That's a drug for HER2-positive metastatic breast cancer. It's an antibody-drug conjugate, so of course the antibody is trastuzumab. With a connector molecule it's connected to ectopic isomer. It's FDA approved for third line metastatic HER2-positive breast cancer patients at this point. At this point it's FDA approved only for HER2-positive, but there are phase two data saying it's active in HER2 low. So even if they are not HER2-positive, let's just say they have HER2 1-plus and 2-plus, this drug may be active. So we have a trial looking at the role of this drug in HER2 low positive patients. So if somebody has ER-positive refractory, or even triple negative refractory, but they have 1-plus and 2-plus, potentially those patients are eligible for this trial. I really think this is a really exciting or really active compound.

Dale Shepard, MD, PhD: Are there any particular trials that you're principal investigator on that are coming up that you're excited about?

Jame Abraham, MD: There is a global trial. We are working on that. It will be called as NSABP B-60 or DESTINY-Breast05. That's a trial with DS-8201, or trastuzumab deruxtecan, in post neoadjuvant HER2-positive breast cancer. So now let's just say somebody has a locally advanced breast cancer, we treat them with TCHP or one of the Herceptin pertuzumab containing regimen. Then after the new adjuvant chemo, the patients go for surgery, and then if they have any residual disease, they will get T-DM1. That's based upon the data, which has to show a substantial improvement in disease-free survival when we use T-DM1 instead of trastuzumab or pertuzumab. That's the new standard. Now we are designing a study comparing T-DM1 versus this DS-8201, trastuzumab deruxtecan, in post neoadjuvant setting. It's going to be a global trial. We are expecting about 1600 patients to be enrolled in this trial.

Dale Shepard, MD, PhD: So it's going to be a large trial, and it seems like it's going to be a while before we get results.

Jame Abraham, MD: So this could be... So in US, NSABP is leading this trial. In Germany, it's going to be German Breast Cancer Group, GBG, and then it will be open in Japan and other parts of Asia. It's a multi... If I can say multinational trial, so we'll see. Some of these trials, when it's open globally, accrue really fast.

Dale Shepard, MD, PhD: When you think about how we're providing trials to our patients, how have we been working toward engaging our regional hospitals, our family health centers, our community partners? How have we collaborated with them to get patients involved in breast cancer trials?

Jame Abraham, MD: We can divide this into two. One are regional doctors, and one, we can say, are other referring doctors from the rest of the state or outside the state. So regional doctors, we engage them through two mechanisms. One, we discuss what trials every time in the tumor board. Dr. Moore, who is the director of the breast cancer program, does an outstanding job. Every time when we talk about any patient from the region, she would pull up our trial list, and show that, and say, "Okay, this patient may not be eligible, but in this setting, we have this trial." That kind of keep bringing to our attention we have potential trials. So keep discussing in the tumor board. That's a huge, huge step. Then the second thing, as you know in our disease oriented group, the doc meetings, our regional research nurses, and some of the regional doctors are calling in. That's a really good way of continuing to educate our regional colleagues around the state.

But I think for our referring doctors, I think, I see the patients come here because of probably two ways. One, patients self refer them. They come here to see Dr. Shepard, or to see Dr. Moore, or another. So they come because of the name. Then second, they are sent to us by the local doctors for a second opinion or clinical trial. So I think we need to continue to educate the patients directly. Then of course, like what you're doing now with the podcast and other ways of reaching out to our referring doctors. We need to continue to educate the importance of clinical trial because, as you know really well, only less than 7% of adult patients go on clinical trial. We can do much better than that, and we really believe clinical trial is the gold standard of cancer treatment. We need to do better.

Dale Shepard, MD, PhD: So in terms of reaching out specifically to patients within breast cancer trials and breast cancer care, how big of a role does social media, patient support groups, how big of a role does that play in terms of patient awareness of a trial and coming here, or something like that?

Jame Abraham, MD: Really good question. So breast cancer, if I can say we are fortunate to have really engaged patient advocacy groups. So there are many different advocacy groups, and I have to say, I'm inspired by the way they engage. I mean, we go to San Antonio Breast Cancer or ASCO, we meet with them. We see them. We engage them. We communicate with them. They are really active on the social media. They follow many of us, many of us in this thing. They know who are breast cancer doctors. They follow us, that we continue to educate, we continue to publish our personal data on social media. Then if we have a new trial, I post that on the social media. The really interesting thing is, let's just say... and I think that's really true. When I say, "Oh, the overall response rate is 60%, and the improvement and survival is whatever, X months," the patients, they will push me back and say, "Really? Are you going to be happy with that X months?"

So I think that's what we want. We want them to bring us to reality and keep pushing us to do better. So I think social media plays a major role, and then I'll give you an example. We work with actually Megan Kruse. Dr. Kruse, one of our colleagues is really playing a major role in lobular breast cancer. We connected with lobular breast cancer advocacy group. We organized a meeting over here. We are really part of Lobular Breast Cancer Alliance, social media engagement. We always connect with those groups. Another group is metastatic breast cancer group. We really connect us, breast cancer providers and myself, with this patient advocacy group. They play a major role.

Dale Shepard, MD, PhD: So certainly that gets the word out for patients to look for us and look for trials. I guess, doubling back a little bit on more involvement of people away from main campus, a more common cancer like breast cancer, is it possible, or what works best in terms of trying to bring patients here to participate in the trials, or taking the trials and putting them out in the region with a more common cancer like breast cancer? Is that, is that an effective strategy?

Jame Abraham, MD: That's a really good strategy. So, at least for breast cancer, what they're doing is like phase three trials. Of course we have a standard treatment and we're testing something new, but phase three trials, adjuvant phase three trials we are putting out in the region. So we really have huge success. We're looking at adjuvant palbociclib and adjuvant abemaciclib. So all those trials are actually, when accrued, a fairly high roll in from the region. Then when it comes to phase one, of course, as you know, you lead the phase one program. Phase one, even breast cancer phase one, we do mainly at the main campus. There's some phase two, some phase two with less, if I can say, complicated schema and less complicated patient visits, or with no pharmacokinetic stuff, then that can be done in the region too, looking only for efficacy data. So phase three, definitely region. Phase one, predominantly main. Phase two can be a combination of main and region.

Dale Shepard, MD, PhD: So in terms of clinical trials, was there anything that you found particularly compelling at ASCO this year?

Jame Abraham, MD: Two or three trials. One, there was a trial in breast surgery in metastatic breast cancer. So Dr. Kahn, this is an eco trial, which is presented by Dr. Khan from Northwestern, which looked at what's the role of removing breasts when a patient presented a stage four disease. It didn't show any survival advantage for removing or doing a breast surgery for one of her patient with metastatic disease. The background is there are probably three trials presented in the past.

Dr. Khan actually did a retrospective study, which actually showed a survival advantage, and then there were a Turkish trial and an Indian trial which showed no survival advantage. This is probably a little more definitive data saying there's not survival advantage for doing breast surgery. I think that's, if I can say, a study with practice impact. Another trial, which is not exactly new, but it was presented at ASCO, roll of trastuzumab, trastuzumab in DCIS. That's a NSABP trial, which looked at giving two doses of... I mean, trastuzumab in DCIS-positive patients. It didn't show any survival benefit. So there was no really practicing thing interesting, but these were interesting trials.

Dale Shepard, MD, PhD: So of course you have San Antonio Breast, but ASCO certainly is a huge forum for people to interchange ideas. With it being virtual, do you foresee either a positive or negative impact on new trials in breast cancer? Not necessarily being able to interact directly, but maybe having people involved that wouldn't ordinarily? What do you think about the virtual format for conferences and impact on trials?

Jame Abraham, MD: I mean, conferences provide many testing for us, and if I can say, of course we learn, but most importantly, the conferences provide as a platform to meet people. That's huge. We can always say, "Well, it's really easy to stay home and look at the computer," but meeting people, sitting down for a coffee, that's huge. I think that connecting people directly, we're going to miss that. People from around the country, around the world, from other institutions, and then industry, and publishing world, and patient advocacy groups. I think that will be a huge miss.

Dale Shepard, MD, PhD: So when we think about breast cancer trials, what's ongoing? What's upcoming? What are your concerns about the gaps? What's the real need that's being missed? Is there anything being missed?

Jame Abraham, MD: There were some early data on role of CDK4/6, but particularly abemaciclib in ER-positive early breast cancer. So we are always... In estrogen receptor positive patients, of course we treat them with endocrine treatment, and in metastatic setting, we know that CDK4/6 can definitely double the progression-free survival. Some of the CDK4/6 inhibitors, like ribociclib, increase the overall survival. We've been really looking forward to see CDK4/6 data in adjuvant setting. We were part of many trials, and one of the trials was palbociclib. Palbociclib didn't show SLR, at least from the preliminary data, and the impact on survival is minimal, but abemaciclib part of the trial NSABP-58 that the early results which is released by the investigators shows the survival benefit for adding abemaciclib in ER-positive early breast cancer. So that's exciting, and we are hopefully in one of the future meetings ASCO or SABCS, we will learn more about it.

Dale Shepard, MD, PhD: Well, thanks for all of your insights on clinical trials, Jame. Is there any additional comments?

Jame Abraham, MD: No. Thank you so much. This is exciting. This is good. Again, stuff what you are doing, if this is interconnecting with our referring doctors will be a huge help for clinical trials and other stuff.

Dale Shepard, MD, PhD: All right. Well, very good. Thank you.

Jame Abraham, MD: All right. Thank you.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/cancer-advances podcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. Don't forget you can access real time updates from Cleveland Clinic's cancer center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.