Refining Treatment Approaches for HER2+ Breast Cancer - Episode 13

Decision Factors for SubQ Therapy and Unmet Needs

March 5, 2021
Joyce A. O'Shaughnessy, MD, Baylor Charles A. Sammons Cancer Center

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Lisa Carey, MD, FASCO, UNC Lineberger Comprehensive Cancer Center

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Vijayakrishna Gadi, MD, University of Illinois College of Medicine

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William Gradishar, MD, Northwestern Medicine

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Claudine Isaacs, MD, Lombardi Comprehensive Cancer Center

Joyce O’Shaughnessy, MD: Claudine and Bill, what’s your experience in terms of what kind of considerations you or your practices use in terms of the subcutaneous vs the intravenous? How is COVID-19 [coronavirus disease 2019] factoring into it? It hasn’t been around that long. Have things changed quickly, or is it evolving? How about your, Claudine?

Claudine Isaacs, MD: It just went on formulary for us a few months ago. We started to convert most patients, and we are having the same overwhelmingly enthusiastic, yes-please response to it that others are. It’s going to be the way we do it. It’s a winner for the patients, and it’s a winner for everyone.

We are participating in a study that was looking at home administration, and that started early on in COVID-19. It was a real plus for us because we were on the East Coast and we got hit early on with COVID-19. A lot of patients wanted to participate in that study because it kept them out of the hospital; it kept them at home. But being in the hospital for shorter is a win-win.

Joyce O’Shaughnessy, MD: How about you, Bill? What is going on at Northwestern? Has COVID-19 played a role?

William Gradishar, MD: It was relatively recently approved, so we’re just starting to use it. I’ve done it in a few patients. I can see absolutely no reason why it wouldn’t be the win-win that everybody is describing. I don’t know why anybody wouldn’t want to do it, unless they had a child at home they needed to escape from. Short of that, it seems completely reasonable.

For COVID-19, anything that keeps people away or limits their time is attractive to patients. That’s another reason, but I don’t think we’ve treated enough people to say what our experience is in any big way.

Joyce O’Shaughnessy, MD: We really covered the waterfront. We hit all the new data and all the new things people have to know to optimize HER2 [human epidermal growth factor receptor 2]–positive patients’ care in the early stage metastatic phase. Thank you. It’s really been a rich discussion and very comprehensive.

Let’s finish by going around the room. If anybody wants to leave with a parting thought: what you’re really happy to have in the clinic, something you’re interested in or excited about, what you’re looking forward to, or an unmet need that we’re looking for. VK, do you want to start?

Vijayakrishna Gadi, MD: Two thoughts. One, I was sitting next to an advocate in 2019 at the San Antonio Breast Cancer Symposium sessions, where all these amazing abstracts about HER2 disease were coming by. She does not have HER2+ disease, and she turned to me and said, “I have HER2 MB [metastatic breast cancer].” That captured the sentiment of what we’ve done and what we’ve been able to achieve for this patient population with so many options. Many of these patients will still die of this disease. This is more optimistic than I’ve been about a space in a long time. For that I’m grateful.

I’ll close with 1 bit of data they kind of snuck in at the San Antonio meeting, which was from the SUMMIT trial. This had to do with neratinib. I know we don’t think about it in the same way, but there are patients who have HER2-activating mutations. If we look for them, we’re going to seem 5% to 10% of the time in all these different disease settings—that’s triple negative, ER [estrogen receptor] positive.

It turns out that neratinib and probably some of the other HER2 tyrosine kinase inhibitors will work well for these patients with activating mutations, and I’m looking forward to more of that data so we can expand the net of patients who we use the HER2-targeted therapies for.

Joyce O’Shaughnessy, MD: Thanks. How about you, Lisa?

Lisa Carey, MD, FASCO: A couple of thoughts. First, I’ll double down on what VK said: Our friends who take care of patients with pancreatic cancer are not having conversations or arguments about whether to call it optimizing, de-escalating, tailoring, or precision. The armamentarium and the explosion of opportunities in treating this disease is really so remarkable. The trajectory that we’re on, which is to start peeling back in a rational fashion, is exactly the right direction to go.

Rather than just depending on drug evaluations combined with clinical variables, it’s going to involve biological information, either through the tumor or through circulating identification of parameters that are controlling disease behavior. We’re going to get there. We actually are going to have a menu that’s going to be driven by real risk and by likelihood of responsiveness to less toxic things.

We’re going to get rid of chemotherapy. In 5 to 10 years down the road, we may feel like we have a shot at—in some, not all—actually converting some metastatic patients with HER2+ disease to cure. The drugs are that good, and there are many of them. Some of the tumors that we started this conversation talking about are exceptional responders, and we all have them. It’s not like, “I’ve heard of 1.” We all have these patients. This is a real possibility. The armamentarium is going to keep growing.

I’ll leave with 1 last anecdote. I had a patient, she was 1 of my favorite patients, a wonderful person, and she always was always dressed to the nines and ready for her evaluations. She would come in and I could always tell when her tumor was progressing because she had this big liver metastasis. It was her dominant site. When it grew, it would start to give her pain. She would come in looking more bedraggled. You could see her walk in the door, and you could tell that her tumor was progressing. She would get symptomatic. Whatever I did, every time I changed up her HER2, new drugs would come in or a trial would come in with a drug, just as her disease was growing. She must have gone 6 years with symptomatic liver metastasis, because we kept having drugs to change. As we figure out how resistance patterns come up, we’re going to be able to recycle if not the actual drugs, then the approaches. We’ll see more of that.

Joyce O’Shaughnessy, MD: Thank you very much. How about Bill?

William Gradishar, MD: I would echo some of the sentiments that others have already mentioned. Many of us have been around long enough that we’ve seen the arch of how this disease has changed. It’s not unlike when there was carboplatin-paclitaxel: When you’re in private practice, you’re pretty much covered. You could hit about half the diseases you took care of. The challenge and the gift we have now are all these new therapies. It provides an understanding of how far we’ve come because we were treating patients before there was trastuzumab. We’ve seen the evolution of our ability to extend the survival of patients just like the anecdote that Lisa just mentioned. We have a lot of patients like that, where it’s not 2 years anymore. It may not be forever, but it’s 6 and 8 years, and for some patients 10 years.

I suspect that 10 years from now, what we’re doing will make us look like cavemen because we’ll have a lot of new therapies and different ways of assessing the disease than we currently do. It’s a remarkable evolution over a period of our careers.

Joyce O’Shaughnessy, MD: Thank you, Bill. Claudine, how about you?

Claudine Isaacs, MD: It’s hard to add much on top of what Bill said. I echo most of these sentiments, and I think the concept of individualization and optimization is there. Whatever we want to call them—neoadjuvant, adjuvant based—these trials that have been designed and are available through the cooperative groups. When Lisa talked about the CompassHER2-pCR trial and the escalation trials for the patients who only achieve a pCR [pathologic complete response], we’re really going to have better and better markers to figure out who needs what and who doesn’t need other things. We’ll get to a point where we are much more tailored in our treatments.

In the metastatic space, we all have a series of patients who are long-term responders. With all these drugs that are prolonging life, we’re offering better and better options for our patients. We’re going to figure out how we can peel some of it back. I’d love to give tucatinib without capecitabine. We need to figure out those things, because we’re talking about prolonging life and quality of life for as long as we can.

Lisa Carey, MD, FASCO: Yeah, Claudine. And soon.

Joyce O’Shaughnessy, MD: Yeah. Thank you, guys. It’s been nice talking to you all. Thanks for sharing your experiences and your thoughts and everything. I want to thank our viewing audience as well. We hope you found this OncLive® Peer Exchange® discussion to be useful and informative. Thank you.

Transcript Edited for Clarity

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