Enhertu for HER2-positive cancer: How it works and side effects explained

The following questions and responses have been lightly edited for grammatical purposes. 

1) How exactly does Enhertu work in targeting the HER2 protein?

Enhertu is a type of targeted chemotherapy. It’s a targeted chemotherapy that’s given through an IV in an infusion center. It’s part of a newer class of treatments called antibody-drug conjugates.

[You can] think of it almost like a smart delivery system where one part of the drug finds and attaches to the HER2 protein on the cancer cell. It’s like a key finding the right lock, with the lock being that HER2 protein. Once it connects, it delivers a strong chemotherapy medicine directly inside the cancer cell, where it works to stop the cancer cell from growing and spreading.

Here’s something really interesting about Enhertu: the chemotherapy part can also affect nearby cancer cells that might not have any HER2 expression or may have very low levels of HER2 expression. This can make the treatment even more effective in some cases of breast cancer with lower levels of HER2, known as HER2-low.

So even though Enhertu includes a form of chemotherapy in its drug design, it’s designed to be more targeted, meaning it goes mostly to the cancer cells that have HER2 protein overexpression.

Because of this more targeted approach that’s focused on the cancer cells, it may cause fewer side effects and could be a more effective therapy for HER2-positive cancers compared to traditional chemotherapy drugs like Taxol, which affect not only the cancer cells but also healthy cells throughout the body.

2) What are some of the side effects of Enhertu?

I always have to be very cautious when I talk about targeted therapies and immunotherapies because they each have their own side-effect profiles. Like all cancer treatments, Enhertu can cause side effects. Of course, not everyone will have the same experience with these side effects.

Some of the more common side effects include feeling tired and having low white blood cell counts, which can raise your risk for infection because white blood cells are really our first line of defense. You may also experience low red blood cell counts, which can make you feel weak or short of breath. This is a condition called anemia. Other possible side effects include nausea or vomiting, hair loss, constipation, or diarrhea.

One rare but serious side effect we get particularly concerned about with Enhertu is something called interstitial pneumonitis, which is a type of lung irritation. This can cause breathing problems like shortness of breath or a new cough. In rare cases, if left untreated, it can be very serious. That’s why your oncologist and care team will monitor you closely for any signs of lung problems during treatment. If you notice any changes in your breathing pattern or develop a new cough, it’s important to let your physician or oncologist know right away so they can help manage your symptoms.

Also, since Enhertu contains a medicine called trastuzumab, which is the antibody or “key” that finds the HER2 protein “lock” on the cancer cell, your oncologist will also keep an eye on your heart health. Trastuzumab can affect heart function, so you may have a heart test called an echocardiogram, or ultrasound, before starting treatment and possibly during treatment to make sure everything is working as it should.

3) What innovations can we expect in the HER2 space?

I would say it’s such an exciting time in oncology, and it’s been really rewarding to be in this field. I think there’s a lot to be hopeful about when it comes to HER2-positive cancers, and even cancers that have lower levels of HER2, which we sometimes call HER2-low. We’ve been hearing a lot about HER2-low in breast cancer. More research has shown that some patients with lower HER2 expression, especially in breast cancer, can benefit from certain targeted therapies like Enhertu. That means more people might be able to get personalized treatment options that weren’t available to them before. 

I think another exciting area is how we measure HER2. Right now, most HER2 testing is done using a method called immunohistochemistry, or IHC, which looks at HER2 protein levels in a tissue sample. You’ll need a biopsy or surgery sample, and then it’s examined under a microscope.

While helpful, this method can sometimes give results that vary depending on the lab, the pathologist reading it, and how the sample is handled. That’s why researchers are working on newer and more precise ways to measure HER2, such as digital imaging tools that help improve how HER2 expression is scored.

There are also next-generation sequencing techniques, which look at gene changes at the DNA level, and liquid biopsies, which are blood tests that look for HER2 changes by analyzing tumor DNA or proteins shed from cancer cells into the bloodstream.

All of this is helping doctors better understand how much HER2 is present and whether we can target it more precisely with a personalized therapy. The hope is that as we learn more, even more patients, not just those with high HER2 levels, will have access to targeted therapies that are both effective and tailored to their needs.

 Want to learn more about HER2? View part one of our webinar recap where Dr. Ko explains HER2 testing.