David Riseberg, MD, Medical Oncologist, Mercy Medical Center, Baltimore, talks about the new treatments giving patients a fighting chance against metastatic HER2+ breast cancer.
What is happening in the body when someone has HER2 cancer?
RISEBERG: With breast cancer we look at certain receptors or proteins that are expressed on the cancer. They’re important because they can be helpful from a prognostic standpoint. For example, how likely is it someone is going to live and for how long? Some patients are positive for hormone receptors, so estrogen-blocking treatment could be helpful. We also look at the HER2 protein, which is a protein receptor that sits on the surface of some breast cancers. In about 1 out of 5 women who have breast cancer, this protein is highly abundant on the surface of the cancer. When activated, it can lead to cell growth that can cause increased growth of the cancer. The goal is to use that protein to help the woman as opposed to just looking at it as a prognostic factor. From a prognostic standpoint, it’s associated with a more aggressive cancer, and it used to be that we would look at these women before we had drugs that specifically targeted HER2 as having a worse prognosis. There have been several drugs that have come along that target this HER2 protein. Sometimes they target it outside the cell, and sometimes they target it inside the cell. Through this mechanism, we’ve had huge advances in this subgroup of women. They do much better when you treat them with HER2-directed treatment early in their course. If it’s a metastatic disease setting where the cancer has already traveled to other parts of the body, we still find that adding HER2-directed therapy significantly improves the responses in survival.
You had mentioned about 20% of women have this breast cancer. Is that a significant number?
RISEBERG: Well, when you think about a couple of hundred thousand women getting breast cancer every year, 20 % is a large number.
It seems these proteins, for diagnostic reasons, are great. But you are also looking forward to them helping women?
RISEBERG: Right. About 20 years ago, we would see that when the HER2 protein was positive, we knew this was a cancer that was more aggressive. The patient would benefit from chemotherapy, but we weren’t happy about it. Then some people developed drugs that specifically targeted the protein. There was a drug called Herceptin, which was an antibody that binds to this HER2 receptor protein outside the cell and blocks the signaling inside the cell to prevent that cancer growth. It also helps recruit the immune system into helping target the cancer. So, there’s sort of two main mechanisms of action. We’ve also learned that if you add chemotherapy to Herceptin, the survival is much better. So that sort of became the general paradigm for early-stage breast cancer and late-stage, or metastatic, breast cancer. People have continued to develop drugs against this HER2 protein. We’ve learned that in the metastatic disease setting, unfortunately, the Herceptin doesn’t work forever, and you must try something else. There are other drugs that have come along including these two new ones that we’re talking about.
Tell me about the two new drugs. Are they taken separately and were just developed around the same time?
RISEBERG: Correct. They both received approval within a few months of each other, maybe a year or two ago, and are both exciting. This drug in HER2 is an antibody-drug conjugate, which means it’s the Herceptin antibody and the chemo drugs that are chemically bound. It’s given intravenously and then binds selectively to the cancer cell. The chemo drug is then released, and it goes predominantly inside the cancer cell. That’s done to help reduce some of the side effects, not just going everywhere but mainly inside the cell. This has been shown to be very effective in a group of women who had a median of six prior treatments for their breast cancer. These were women who were heavily treated. The second antibody-drug conjugate that’s been approved has the same concept. It is a newer drug that is being used after women have had Herceptin and after having had the KADCYLA drug (first antibody-drug conjugate). In studies, they’d had many other treatments as well and the response rate was 60%, even in this heavily pretreated population. The cancer didn’t grow for a year and a quarter or so for women who were receiving that drug on average. So again, that’s not 10 years but it’s significant when you’re talking about women who’ve had a lot of treatment for their breast cancer. It’s an exciting finding and they got approval based upon this early study with additional studies ongoing. There are also studies looking to move it earlier in the line of treatment as well.
Which of the two is Joyce on?
RISEBERG: She is currently on HER2 and has participated in a clinical trial in which everyone got the KADCYLA drug and then a pill which was either TUKYSA or a placebo. So, we don’t know which one she got.
I know the drugs were developed at two separate times, but is it possible for doctors to step to another drug if needed?
RISEBERG: So, you can go from one to the other. Again, there’s no current rule for combining them. Now, the TUKYSA is a pill and it’s given in combination with Herceptin and another chemotherapy drug called Capecitabine or Xeloda, which is in pill form. So, it’s three drugs, one IV Herceptin and two oral pills. That combination was studied in a similar group of women, as HER2 was, who had several lines of previous treatment. They had a significant improvement in overall survival at two years. Women with brain metastases is an important population because the HER2-positive breast cancers tend to want to go to the brain. Up to half of all women with HER2-positive breast cancer, when it spreads, it will ultimately involve the brain. Sometimes, these larger molecules don’t cross the blood-brain barrier very well. So, a small molecule drug like TUKYSA or Tucatinib has been thought to be potentially more effective. In this study, around 25% of the women who were on the three-drug combination had gone one year without having the cancer progress and none had gone without having the cancer progress amongst the women who had brain cancer.
How important is it to have these extra tools?
RISEBERG: It’s critical because women are living longer. When I started my career in the mid-’90s, they weren’t even testing for HER2. Now that we have these HER2-directed drugs, women are living their longest. And particularly those that are hormone-receptor-positive and HER2-positive. So, the more things that we have that are options that have effectiveness and maybe a somewhat different mechanism of action, the better we can treat these women for longer periods of time. The other nice thing is that they have side effects but not too bad compared to some of the other drugs we have. However, I don’t want to minimize the potential for side effects. Sometimes it can be serious, but in general, the quality of life of women is good compared to women that are on traditional chemotherapy.
Can you tell me a little bit about Joyce?
RISEBERG: I’ve known Joyce for several years. She was one of those women who, unfortunately, despite having a relatively early-stage breast cancer, it came back years later. When I first saw her when she had a recurrence, she was naturally devastated. We discussed the implications of having a cancer that has returned, but quickly shifted into tell me what I got to do. She was sick initially but, fortunately, responded well to the first treatment. Her quality of life improved, but she was someone who never complained that much. In the infusion center, she has sometimes talked to some of the other women and has been inspirational. I know that others have commented about her and how she’s just a positive influence when she talks. The nurses all respect how she battles and how she has focused on the positives and doesn’t tend to dwell on the negatives.
What was Joyce’s first treatment?
RISEBERG: When she had the recurrence, the first round of treatment included Herceptin and chemotherapy. Then, she went on the study and then went in HER2.
How is she now? Is she disease-free? Is it stabilized?
RISEBERG: It certainly has stabilized and has improved since going on the HER2.
When she was diagnosed, do you remember what stage it was?
RISEBERG: Originally, she was a stage one or two. I forget exactly. But I think she was just on an estrogen-blocking pill. Once she recurred, the cancer had become HER2-positive and had spread to her liver.
Is there anything I didn’t ask that you would want to make sure people know about regarding these new drugs?
RISEBERG: In cancer treatment, there’s been a movement towards trying to identify certain molecular markers that may be prevalent on this person’s cancer but not that person’s cancer. And, seeing if there is a drug that could specifically target that molecular change where maybe it’s more specific to only a small percentage of that type of cancer, but can be more effective. Oftentimes, those drugs tend to be less toxic than traditional chemotherapy. I think that the survival of women, or people with cancer in general, is improving in part because we have more of these targeted therapies.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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