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Home Runs and Hope for HER2+

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Published on March 6, 2020

Key Takeaways

“We have a couple of drugs that I would really call home runs,” says expert Dr. Julie Gralow, from the University of Washington, as she discusses research on several agents in development and what they mean for the future of treating HER2-positive breast cancer. Watch as Dr. Gralow shares promising clinical trial data on targeted therapies for advanced Her2+ breast cancer, including those with brain metastases.

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Transcript | Home Runs and Hope for HER2+

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrea Hutton:       

Hello. I'm Andrea Hutton from Patient Power, and I'm very excited to be here at the San Antonio Breast Cancer Symposium, the largest breast cancer conference in the world. And today, I'm very excited to have with me Dr. Julie Gralow, who is the Director of Breast Oncology at the University of Washington in Seattle. And as a breast cancer survivor myself, I have met Dr. Gralow quite a few times. And although she's not my doctor, I'm very excited to be talking to her today.

So, Dr. Gralow, I'd love to hear your take on a few things that we've learned so far, and where the future is. So, there's also information now about new anti-HER2 therapy.

Dr. Gralow:              

Yeah.

Andrea Hutton:       

So, HER2-positive being another type of breast cancer, subtype of breast cancer, and we've had some drugs that have worked well, but now there are some other conversations that are happening about what's next. So, what...

Dr. Gralow:              

Right. I think that's some of the biggest excitement that we've seen here at the San Antonio meeting, because I actually think we have a couple of drugs that I would really call home runs. And that's rare at these meetings to really get home runs where you think the drugs are going to be approved fast and, on the market, and really change the standard of care quickly. So, right now, we have five FDA-approved, HER2-targeted drugs, and HER2-positive breast cancer is about 20 percent of breast cancer.

Andrea Hutton:       

I'm one of those. 

Dr. Gralow:              

You are. There you go. And so, we had a whole session where we had presentations on several new agents. The first was a drug called tucatinib. It's an oral HER2-targeted therapy. And what was impressive about this study was that almost half the patients enrolled had active metastases in the brain. It wasn't that they'd been treated, and they were quiet, but actually they were new brain metastases.

And for all the patients who enrolled, and also the 50 percent or so who had brain metastases, this was a very active drug when given in combination with some chemotherapy and trastuzumab (Herceptin). And it didn't just show response rates, it showed longer time compared to a previous standard of care until the tumor grows again, and also patients lived longer.

Andrea Hutton:       

Most importantly.

Dr. Gralow:              

And that's the most important thing. So, tucatinib, an oral agent, easily penetrates the blood-brain barrier, excellent for brain metastasis, but also seems to have good activity in other parts of the body. This drug isn't FDA approved yet, but I'm guessing that the timeline will be in the next six months or so.

Another home run is an antibody drug conjugate that targets HER2. That's the antibody; it's got a linker; and then it's got chemo attached. And this agent is trastuzumab—that's Herceptin—and it's linked to the chemo which is trastuzumab deruxtecan (Enhertu). And so, this antibody was given—it was just a Phase II trial, no randomization or anything—to patients whose tumors had previously seen multiple previous HER2 therapies. And it showed that virtually every patient had at least some response.

Andrea Hutton:       

So, it's like super Herceptin.

Dr. Gralow:              

One of the most wonderful slides is just looking at the responses in this trial because it's important. Now, there are toxicities. Even though the chemo gets delivered directly inside of the HER2-positive cancer cell, it gets cleaved, and it can leak out a bit. That can have some benefits to the surrounding tumor cells that might not be as strongly HER2-positive. But also, we did see a few cases of really significant what we call interstitial lung disease, and there were a few deaths due to that in the very early trials where they were first trying dosage.

So, we're going to have to pay attention to that. Overall, the percentage of patients that got some degree of lung toxicity was about 8 percent, but most of that was minor. But anytime you see a death due to a toxicity, you have to understand who was that? Could we have prevented it? Could we have picked up signs ahead of time? So, a very active agent. I think we'll figure out the lung stuff and just be watching for it and stop it if we see it.

Andrea Hutton:       

So, that has more studies following... 

Dr. Gralow:              

Absolutely. But I also think there's enough data there because it was done in a population where they'd had lots of prior HER2 therapies, and there's no drug approved after that. So, I think it will likely get approved just based on Phase II data, at least preliminarily, while we wait for further studies that better tell us where it should go. Should we use it earlier line instead of after you’ve already seen a bunch of therapy? Should we put it in the adjuvant setting before you even relapse? So, exciting.

A third HER2 drug that is a new drug, a new concept, and it just wasn't as wow, but I think it's a good drug; we're just not using it right. It's basically a version, if you will, of trastuzumab/Herceptin. But the end of it, what we call the FC-binding ARM, where you can bring in immune cells, and complement and invoke the immune system—it's been changed so that it will enhance your own body's immune response, coming in and recognizing this antibody. So, the HER2 antibody binds to a HER2 cell, shuts down signaling, which is one way it works, but then brings in the immune system and says "hey, look at me. I'm not supposed to be here."

So, margetuximab was tested. It didn't meet what we call progression-free survival endpoint compared to the prior standard of care. It wasn't whopping, a few months' difference. It hasn't yet, although it's early, made a survival difference. But I'm not sure that—it's a good drug; it has activity—but I'm not sure that's the setting I would be most excited about using it in.

And so, I think what we have to do is go back and test this in a setting where we're revving up the immune system in other ways—for example, in combination with immune checkpoint inhibitors, and we're really maximizing the difference of what this antibody is. It's designed to work with our own immune system. And so, I think this is a good drug, but I think we need some studies that really help it stand out in terms of what its role will be. 

Andrea Hutton:       

Well, it's interesting because when I come to these things as a patient, you keep thinking that what you're really here for is the big, breaking news about the newest drug that no one has used yet, except in clinical trial, and it's coming out. And sometimes, these things take a little bit longer, but just because there wasn't whopping news necessarily doesn't mean there won't be another way to find that big breakthrough a little bit longer along the line.

Dr. Gralow:              

Right, exactly.

Andrea Hutton:       

You have to keep looking for those as well. But it sounds like there's still great news coming out of this conference and other...

Dr. Gralow:              

...really hopeful, really exciting. I think we've got some good new therapies that will be available soon. I think we've got further information to better help us direct the appropriate therapy to the appropriate patient. And that's really what it's all about.

Andrea Hutton:       

Absolutely. Well, thank you so much for always bringing us some more knowledge and hope for our patients and our community. So, thank you, Dr. Gralow.

Dr. Gralow:              

Thanks, Andrea.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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