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Treatments for HER2+ Breast Cancer Unveiled

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Published on January 23, 2020

Key Takeaways

  • Fam-trastuzumab deruxtecan-nxki (Enhertu) is a new treatment for advanced HER2+

    breast cancer.

  • Even more new treatments for HER2-positive breast cancer are on the horizon.

  • Clinical trials are the only tool for discovering new treatments.

New targeted therapies for HER2-positive breast cancer are on the horizon, and some are already FDA-approved. Expert Dr. Sara Hurvitz, from UCLA Medical Center, discusses response rates from clinical studies and what these trial results mean for patients with advanced metastatic breast cancer. Watch as Dr. Hurvitz also talks about how patients can find clinical trials that are right for them.

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Transcript | Treatments for HER2+ Breast Cancer Unveiled

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, Patient Power breast cancer community manager and also breast cancer patient, and I'm very excited today to be talking to Dr. Sara Hurvitz, who is associate professor of medicine at UCLA.  Dr. Hurvitz, thank you so much for joining us today. 

Dr. Hurvitz:

Thank you for asking me. 

Andrea Hutton:

And I know that there's been a lot of news right now about some exciting things that are happening specifically for HER2-positive breast cancers.  I was wondering if you could share with us a little bit about what the news is and what that might mean for patients in the clinic and how soon they might be able to access these medications. 

Dr. Hurvitz:

Absolutely, yes.  San Antonio Breast Cancer Symposium was really exciting this year.  There were two clinical trials that were presented that I think were pretty exciting and actually may change practice in the next several months. 

So the first one was a study evaluating a drug called tucatinib, which is a pill.  It's a pill that's similar to drugs like lapatinib (Tykerb) or neratinib (Nerlynx).  It's a medicine which actually targets specifically HER2, and it's a small molecule so it can get inside the cancer cell that has HER2 and block the inside of that HER2 from acting.  

And the difference between tucatinib and these other drugs that have already been approved for HER2-positive breast cancer is that it's really specific.  It's really selective for HER2, so it doesn't hit other receptors that can cause a lot of side effects, one of those being a receptor called epidermal growth factor receptor, EGFR.  We all know that drugs like lapatinib and neratinib can cause a fair amount of diarrhea and even rash.  This drug, the hope was by specifically going after HER2 it would omit that side effect. 

And there was a big Phase I study that showed very promising data with this drug when combined with an oral chemo called capecitabine (Xeloda) and then trastuzumab, otherwise known as Herceptin.  It showed very good response rates, so they did a Phase II randomized trial to see does adding it to those agents really improve outcomes from patients. 

Now, the other really unique and important finding or important feature of this drug is that it's able to cross that sacred blood‑brain barrier, the network of blood vessels that block drugs from ostensibly getting into the brain.  We know for HER2-positive breast cancer a third to half of those patients affected with metastatic disease of HER2-positive will develop brain metastases, so we're looking for drugs that can get into the brain area and help fight cancer there.  And in their Phase I study they showed some very promising activity, again, about 40 percent of patients that had brain tumors shrink on this drug.  

So this randomized trial, which was called HER2CLIMB, actually two‑thirds of the patients received tucatinib plus capecitabine and trastuzumab.  The other one‑third had placebo plus trastuzumab and capecitabine.  And what was really extraordinary about this study is that when they reported the data they showed not only did patients who received tucatinib lived longer with their disease being controlled, so‑called progression‑free survival, but they also showed patients lived longer, period.  End of sentence.  So to show an overall survival benefit is really our gold standard.  That's what we want to go for. 

And then finally they also showed that if you just looked at the 50 percent or so of patients who had brain metastases when they went on to study their progression‑free survival was also improved with this drug, sort of implying that the drug is active here.  So I think these data are incredibly exciting for patients whose disease has been—has shown resistance to trastuzumab and other standard therapies, pertuzumab (Perjeta) and T‑DM1, and my hope is it's going to be available for patients in 2020, that the FDA will approve it.  So I'm very excited to hear what will happen about that. 

The second drug that really splashed was called DS-8201-a.  The other name for it is trastuzumab deruxtecan (Enhertu).  This is kind of like T‑DM1.  It's an antibody that targets HER2 that's linked to chemotherapy.  And the chemotherapy is delivered to the cancer cell by the antibody and released once it gets inside the HER2-overexpressing cancer cell.  And in this trial—this was just a single‑arm Phase II trial to confirm the activity and safety of this molecule in patients whose disease had progressed after multiple lines of therapy.  In fact, like half the patients had had six or more prior lines of therapy for metastatic disease, very heavily pretreated. 

Just to give you kind of a frame of reference, we get really excited when we see 20 percent of patients have disease shrinkage when they've had that much therapy before.  This study showed over 60 percent of patients had their disease shrink, 6 percent of them had it completely disappear, and the median progression‑free survival is over 16 months—again, just kind of blows other studies we've seen in this arena out of the water. 

So I think those data are very compelling, and in fact today marks the FDA approval of this drug.  It was just announced that it has been FDA-approved for HER2-overexpressing breast cancer, so we'll be seeing this in the clinic and as soon as January for our patients with heavily pretreated disease. 

Andrea Hutton:

So that was part of my question, is so the approval currently is for patients who have already had a lot of treatment.  This is not going to be the first treatment that they're offered.  This is likely to be for patients who have advanced HER2-positive breast cancer that has had progression in other treatments. 

Dr. Hurvitz:

Yeah, absolutely.  Yeah.  We're not going to be using it yet in the curative setting, so this isn't replacing your trastuzumab, pertuzumab in the curative setting and now you're T‑DM1.  And we're not using in the first line or second line setting, in the metastatic disease setting.  We're still going to be using trastuzumab, pertuzumab, T‑DM1, but third setting and beyond it's open.  And that's probably where I would utilize this.  If a patient has already been treated with trastuzumab and T‑DM1 or trastuzumab emtansine (Kadcyla) and their disease has become resistant to those agents, this is the drug I would use. 

Now, the reason we don't just all of a sudden use them in everyone, because we're so impressed by the activity is because we haven't yet demonstrated it's better than the agents that have been tested in those settings.  And when I say better I mean not only more effective, but as safe.  Right now we are seeing a signal of interstitial lung disease or pneumonitis with this drug, which is like inflammation of the lungs that can be serious, and in fact on this study four patients died of it. 

So we don't want to become overaggressive in who we treat with this.  Patients have to work carefully with their clinicians to be monitored for symptoms of this, so it can be appropriately managed, and there are a number of ongoing and planned Phase III clinical trials that will address whether or not we can move this agent into earlier line settings. 

Andrea Hutton:

So just for our patients who aren't that familiar with how the different arms of a clinical trial works, so Phase I is small, just to see if it's safe at all.  And then you kind of move through into, okay, is it safe and does it work.  And then how does it work compared to the other standard of therapy that we currently have.  Is that… 

Dr. Hurvitz:

Exactly.  Yeah, exactly right.  And Phase I gives us a little inkling of if it's active, but safety is the number one thing and we only have 10, 20 patients, sometimes 30 enrolled in a Phase I.  For this drug there was actually over 100 enrolled in the Phase I studies.  For tucatinib, for example the study I told you about was a Phase II clinical trial that was randomized, but there were so many patients it really was like a Phase III clinical trial, because it was comparing it to a standard of care arm. 

The DS‑8201 study is interesting, because it was a one a one‑arm study.  It was a Phase II trial.  It didn't have a comparator arm, and yet the FDA found it was so compelling, those results that I described, that it provided an approval.  It's going to need to show confirmatory results in these randomized Phase III trials in order to receive full approval.  But right now I think the FDA is wanting to make this available to patients rather than waiting for those Phase III trials to read out, and I think that's the ethical, right thing to do. 

Andrea Hutton:

Well, it's just—all these results underscore the importance of patients participating in clinical trials and that one of the myths that is so important to dispel is that people think, oh, you get a placebo, you might not get any treatment.  But as you're describing, you always get what the standard treatment would be, it's just a question of whether you get the standard treatment with a new drug added to it or the standard alone.  So you're never untreated in these kinds of settings. 

Dr. Hurvitz:

Absolutely.  It's such a critical point, because I think in the past, 50, 60 years ago, there were abuses in clinical research where patients weren't protected.  But it's such a controlled environment now.  Patients' rights are protected, and no patients in cancer trials are left with no therapy.  That wouldn't be an ethical thing to do. 

Andrea Hutton:

And so these are—these drugs are still in study, in trial, so patients who may want to talk to their doctors about these specific HER2—drugs that target the HER2 receptor is to ask them about the trials and if they're qualified to enroll in the trials, etcetera.  Is that the case? 

Dr. Hurvitz:

Absolutely.  Yeah, talk to your local clinician.  If they're not involved in clinical research, there's a website called clinicaltrials.gov that the National Cancer Institute puts on.  We all have to register our trials there and the information you get on trials.  And there's actually a great patient portal where you can put in the features of your tumor, your doctor can help you fill it out, and then it sort of spits out all the different trials that you'd be eligible for and contact information for sites that have the study open.  So every state has multiple sites and regions, and most patients should be able to have access to a study.  

Andrea Hutton:

Well, thank you so much.  It's incredibly valuable information, and we appreciate you sharing your knowledge and teaching us a little bit and offering hope for the future as well for our breast cancer patient community.  

Dr. Hurvitz:

Thanks for having me.  I think it's a great time to be talking about these new therapies, because there is so much hope for the treatment of this type of breast cancer. 

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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