A Background on Early HER2+ Breast Cancer

Transcript: Joyce O’Shaughnessy, MD: Thank you for joining this OncLive Peer Exchange® entitled “Evolving Treatment Patterns in Breast Cancer.” Today, I’m joined by a group of colleagues who are all experts in the field. And during this OncLive Peer Exchange® discussion, we will discuss recent clinical trials that have an impact in clinical practice, including data from the 2018 San Antonio Breast Cancer Symposium. We will consider how these new data will be incorporated into what we’re already doing in clinical practice.

I’m Joyce O’Shaughnessy. I’m chair of Breast Cancer Research and I’m a Celebrating Women Chair in Breast Cancer at Baylor University Medical Center, Texas Oncology, and USM Oncology in Dallas, Texas. Participating today on our distinguished panel is Dr Aditya Bardia, assistant professor of medicine at Harvard Medical School and attending physician, Medical Oncology at the Massachusetts General Hospital in Boston, Massachusetts. We have Dr Adam Brufsky, professor of medicine, associate chief of the Division of Hematology/Oncology, co-director of the Comprehensive Breast Cancer Center, and associate director of Translational Investigation at the University of Pittsburgh in Pittsburgh, Pennsylvania. We have Dr Heather McArthur, medical director of Breast Oncology at Cedars Sinai Medical Center in Los Angeles, California. We have Dr Ruth O’Regan, professor and division head of Hematology Oncology, Department of Medicine at the University of Wisconsin School of Medicine and Public Health, and associate director of faculty development in education at the University of Wisconsin Carbone Cancer Center in Madison, Wisconsin. And we have Dr Tiffany Traina, clinical director, Breast Medicine Service, Memorial Sloan Kettering Cancer Center in New York, and associate professor at the Weill Cornell Medical School.

Welcome everybody, I’m really glad to be here with you all. Well thank you very much for joining us. We have three segments today and the first one we’re going to start off with is early HER2-positive breast cancer, because that’s probably the biggest practice changing information coming out of San Antonio, that we’re going to treat differently on Monday morning. So, let’s go ahead and start with that. Let’s talk first a little bit about what our standard of care was today before we came here to San Antonio. So let’s begin. Aditya, how do you treat women with HER2-positive early breast cancer?

Aditya Bardia, MD, MPH: So for early HER2-positive breast cancer, if someone has stage II or stage III disease our preference in general is to use neoadjuvant chemotherapy that’s HER2 based. One regimen would be ACTHP [trastuzumab and pertuzumab]. TCHP [docetaxel, carboplatin, and trastuzumab plus pertuzumab] would be another regimen that we would consider. And then after the patient has surgery, we give one year of anti-HER2 therapy. Usually it’s trastuzumab-based therapy. If someone has high-risk disease, such as lymph node positive disease, one could potentially add pertuzumab as well. And then after the completion of one year of therapy, we have another discussion about the use of neratinib.

Joyce O’Shaughnessy, MD: Yes, and how do you decide between a TCHP or an anthracycline-based approach?

Aditya Bardia, MD, MPH: So if you look at the outcomes with ACTHP and TCHP in the adjuvant setting, the outcomes are very similar. In the neoadjuvant setting we did a retrospective review where we looked at own experience of ACTHP versus TCHP, and the PCR rates are very similar whether you use ACTHP versus TCHP. So it’s pretty much dependent on the side effect profile. If I have someone who I’m worried about regarding the adverse effects of anthracyclines with cardiotoxicity my preference would be to use TCHP.

Joyce O’Shaughnessy, MD: Well for stage II/III disease it’s pretty much trying to get into the neoadjuvant setting for patients. So how about you, Adam?

Adam M. Brufsky, MD, PhD: Pretty much the same. We tend to use TCHP. I think it’s an interesting dilemma though because ACTHP in many ways is less toxic than TCHP, mainly because you do TCHP with docetaxel. That’s actually a much milder regimen when you think about it. You don’t really need growth factors. I think I use TCHP though almost exclusively in stage II or III breast cancers in neoadjuvant therapy. I think that our experience is similar to yours in that the PCR rate of ER-negative, HER2-positive disease in that setting is in excess of 75% to 80%. It’s really uncommon for someone not to have a PCR. And so that’s pretty much my go-to therapy for stage II and III.

Joyce O’Shaughnessy, MD: And how about you, Tiffany? Because in the northeast there’s a little bit more anthracycline used perhaps in general than the West Coast. How do you guys decide between anthracycline or not?

Tiffany A. Traina, MD: So I think for a higher risk early stage disease, node-positive disease, we truly are still favoring anthracycline-based regimens. But you have to acknowledge, as Aditya said, a lot of the data look very comparable in terms of benefit and using TCHP. And I think what we’re seeing over time is that the benefit from dual HER2-targeted therapy is so significant that it may not be the chemotherapy backbone that’s as relevant as getting the right HER2-targeted therapies in there.

Joyce O’Shaughnessy, MD: So how do you guys decide if you start off with an HP regimen [rastuzumab plus cisplatin] preoperatively, just because I know there’s a little variation in practice. The APHINITY trial certainly had an excellent outcome with the addition of the pertuzumab, regardless of chemotherapy backbone, which is an important thing. But it didn’t treat patients preoperatively. So we’re extrapolating from that disease-free survival benefit that was in APHINITY, but trying to incorporate that into the neoadjuvant setting. So how do you handle that with regards to people’s pathologic CR [complete response (PCR)] rates or not?

Ruth O'Regan, MD: So I think if they’re clinically node-positive, I would probably consider continuing pertuzumab even if they’ve got PCR. If they’re clinically node-negative, I have to say it would be a discussion with the patient. I would tend not to give pertuzumab in that scenario. But, unfortunately, as you point out, the APHINITY trial doesn’t address this so I’d be very interested to hear what other people are doing with regards to that, and obviously we’re going to talk a little bit more because obviously things have changed now.

Adam M. Brufsky, MD, PhD: Yes, they have.

Ruth O'Regan, MD: But I think I would base it on the lymph node status.

Joyce O’Shaughnessy, MD: Correct me if I’m wrong, but what I carry around with me is that the real improvement in disease-free survival was in the node-positive cohort. If you put the ER-positive and the ER-negative together, the node negative group, the curves are on top of each other, plus or minus pertuzumab. But then again we saw that in the ER-negative group there was a benefit from pertuzumab. So that group wasn’t specifically called out, the node-negative, ER-negative. Do you ever continue for the full year?

Heather L. McArthur, MD, MPH: I have to say that I’ve been sobered by the long-term followup from the North American adjuvant trastuzumab trial, the HERA study. It’s with 25% to 30% recurrence rates at 10 years. So I do wonder with the addition of pertuzumab, even if the improvement in invasive disease-free survival at three years was only 0.9%, whether there will be a more marked improvement over time. And so I do think that rational data-driven de-escalation strategies are needed.

Joyce O’Shaughnessy, MD: And what do you do if somebody has a pathologic CR and stage II, III disease, and you’ve started off with TCHP, for example? What do you do based on the path CR, no [pathologic] CR, or their original staging?

Heather L. McArthur, MD, MPH: I have not been making decisions on pathologic CR. I try to make a decision upfront about whether I think this is a high-risk situation or a low-risk situation. I might give the drugs in reverse: give THP before surgery just to get that look, to get a sense of whether they had a response. But I still often give AC on the back end if it’s a 25- or 30-year-old patient with node-positive disease, and then resume HP after the completing year. But I think this is all in flux, obviously, at the moment.

Transcript Edited for Clarity

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