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HER2-Positive Breast Cancer Treatment: What's Ahead?

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Published on July 30, 2020

What New HER2-positive Breast Cancer Treatments are Coming?

As a breast cancer patient, you may be thinking, "I’m doing well on the treatment I'm on now, but are there other options for me if these drugs stop working?" Are there new drugs in the pipeline for HER2-positive breast cancer?

Dr. Erika Hamilton, from the Sarah Cannon Research Institute, discusses new treatment options for breast cancer and explains how HER2+ treatment is becoming more personalized. Dr. Hamilton says that “We're at a great point that we have more drugs available in our arsenal, and now we get to fine-tune or tailor when to use them.” Watch as she shares encouraging clinical trial data from the KATHERINE study, and what exciting developments she anticipates in breast cancer research.


Transcript | HER2-Positive Breast Cancer Treatment: What's Ahead?

Dr. Hamilton:
I think for patients it's always exciting to have new options, right? Because always in the back of your mind you're thinking, "I may be doing well on what I'm on now, but how many more things are there for me if those drugs stop working?" And so I think it's very encouraging to see new drugs come out.

I think the other thing that we're doing a better job of, honestly, in drug development is figuring out who needs which medicines. And so a good example of that was the KATHERINE trial. And this is a little bit older, but still relatively new, where this trial, we used T-DM1 in the adjuvant setting, so after surgery. And they designed this trial a little bit differently than trials had traditionally been designed in the past. In the past, we used to define these high-risk trials based on, how big was somebody's cancer? Was it smart enough to get to the lymph nodes? How many lymph nodes were positive? And in KATHERINE, instead they defined a high-risk population based on whether somebody had had a pathologic complete response, meaning all of their cancer had melted away at the time of surgery. And so if somebody's cancer hadn't melted away, those were the patients that were allowed to go onto the KATHERINE trial, randomized against standard HER2 antibody versus T-DM1. And what we saw was really a much bigger magnitude of benefit there, 11% improvement in disease-free survival, from 77 up to 88% in the adjuvant setting, than we'd really seen before. And I think that was because we designed the trial better. We took people that were truly high risk, where they needed that therapy, and we could see a bigger benefit.

And so I think this idea of finding the right size therapy for the right patient is really exciting and something we're doing more and more of. We often use the term escalation and de-escalation for this, which I think is probably not as precise as we want to be and can be confusing to a lot of patients too. Nobody really wants to be de-escalated. It doesn't sound like it's something we want to do. But what it really means is not giving somebody more therapy than the need. Or similarly, somebody that's going to maybe not have a great outcome, being able to give that patient more therapy. So I like this idea of right size for the right patient.

One thing that we've seen a press release on but have not seen data yet is MonarchE trial, which is the adjuvant abemaciclib (Verzenio), the CDK4/6. We've heard that those results are positive, and so we anticipate seeing those soon. That's something I'm really excited about and gets back to that right size for the right patient. It offers us something above endocrine therapy alone at those patients that are very high risk for recurrence, so I'm very excited about that.

 And then I think something, if we go back to HER2, which we talked a little bit about at the beginning, we're going to see trastuzumab deruxtecan (Enhertu) and tucatinib (Tukysa) moving up earlier. They have ongoing trials versus T-DM1, or in combination with T-DM1. I think we're going to see both of those compounds even going up earlier into early stage disease as well. But I'm excited about kind of refining when to use these drugs. We're at a great point that we have more drugs available in our arsenal, and now we get to kind of fine-tune or tailor when to use them.

And then I think one of the class of drugs that I'm most excited about, similar to the lines of antibody-drug conjugates, where we kind of got this two-sided molecule, are some bispecifics where instead of just having a simple antibody that binds to one place it's kind of a two-headed antibody where it binds to one thing on one side and something else to the other. And that's being used a lot right now in HER2. A couple different flavors of this. We can bind both the pertuzumab (Perjeta) and the trastuzumab binding site. We can bind HER2 and then also bind the immune system, which is really exciting and possibly a way we can kind of bring a different flavor of immunotherapy to HER2-positive disease. And so those are some drugs that are in development right now that I'm excited about.

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