Joyce O’Shaughnessy, MD: Hello, and welcome to this OncLive® Peer Exchange® titled “Refining Treatment Approaches for HER2+ Breast Cancer.” I am Dr Joyce O’Shaughnessy from the Baylor University Medical Center, Texas Oncology, and US Oncology in Dallas, Texas. I’m delighted to have 4 friends and longtime colleagues with us to debrief after San Antonio Breast Cancer Symposium and find out what people thought about some of these data.

I have with me tonight Dr Lisa Carey from the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina; Dr VK Gadi from the University of Illinois College of Medicine in Chicago, Illinois; Dr William Gradishar from Northwestern Memorial Hospital in Chicago, Illinois; and Dr Claudine Isaacs from the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC.

Today we are going to highlight a number of topics pertaining to systemic treatment of HER2+ [human epidermal growth factor receptor 2–positive] breast cancer and the impact of recent clinical trial data on clinical decision-making. In addition, we’ll be covering key clinical data from ESMO [European Society for Medical Oncology Congress] 2020 and San Antonio 2020. That’s what we’re going to be talking about over the next about hour and a half or so.

The first segment is dedicated to HER2+ early stage breast cancer, looking at the neoadjuvant and adjuvant settings. We’re going to start with early stage and go to metastatic next. First, it’s probably going to be helpful to set the stage looking at the standards of care—where are we today—and then we can look at where we’re going. Lisa, can you give us an overview of where we are today?

Lisa Carey, MD, FASCO: With early breast cancer in the HER2 space?

Joyce O’Shaughnessy, MD: Yes.

Lisa Carey, MD, FASCO: What’s changed and what is certainly true nowadays is that for the majority of HER2+ breast cancer patients, we’re treating them in the neoadjuvant setting. They’re getting their chemotherapy and anti-HER2 targeting, for the most part, preoperatively, and then HER2 targeting postoperatively is predicated on extent of disease that’s found at surgery. There’s a reason for that. It’s better for surgical end points. Clearly you can create more lobectomy candidates, and you can reduce the need for axillary dissection. Moreover, from the medical oncologist’s standpoint, we all have the great data from KATHERINE with the shift to T-DM1 [trastuzumab emtansine], improving outcomes in those with residual disease.

The group that’s still treated with adjuvant therapy is stage I, T1N0. Many of us, in order to confirm that they would fit into these—we call it de-escalated, although that’s a term I’m trying to train myself not to use because the patients hate it. The APT regimen was just 12 weeks of paclitaxel plus trastuzumab in continuation of that. That’s the standard general framework. The debates that are going on is what’s the appropriate chemotherapy backbone, and do you need an anthracycline, for example? What’s the extent to which we need all those drugs and whether we can rationally optimize therapy even in the higher clinical risk patients?

Joyce O’Shaughnessy, MD: What do you tend to use, Lisa, in the neoadjuvant setting for preoperative treatment?

Lisa Carey, MD, FASCO: I typically use TCH [docetaxel, carboplatin, trastuzumab]. I will add pertuzumab if the patient is clinically node positive.

Joyce O’Shaughnessy, MD: What if they have a tumor like a T2 or T3 but are clinically node negative as far as you can tell?

Lisa Carey, MD, FASCO: I still use TCH. The APHINITY data that we’ll talk about a little later. I’ve been fairly convinced that the marginal benefit of pertuzumab is relatively small in the node-negative setting.

Joyce O’Shaughnessy, MD: How about other people? Any other points you would like to make around the state-of-the-art therapy for patients? What about anthracyclines? Does anybody still use anthracyclines? Somebody could just mention with the TRAIN-2 data, for example.

Vijayakrishna Gadi, MD: I’ll jump in on the anthracycline piece. For patients who have substantial burden of disease—maybe somebody who has not screen detected but walks in with a big mass—I frequently start with a taxane portion, and then I’m on the fence a little on the anthracycline. Most of those patients still end up seeing the anthracycline in my practice.

Joyce O’Shaughnessy, MD: How about you, Claudine?

Claudine Isaacs, MD: I shifted a little while ago more toward TCHP [docetaxel, trastuzumab, pertuzumab, carboplatin], although I do find that it’s a difficult regimen. From a symptom-control perspective, it’s 1 of the toughest regimens we give. ACTH [doxorubicin, cyclophosphamide, paclitaxel, trastuzumab] or AC-THP [doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab] is an easier regimen to take.

But the TRAIN-2 data were further evidence for us that the anthracyclines really didn’t add much. Because you minimize the cardiac toxicity risk again, that risk is not sky-high, but it is marginally higher with the AC-THP than it is with the TCHP. I’ve predominantly shifted to TCHP unless I’m treating a patient on a clinical trial. We all have a few patients here or there who have synchronous tumors, and 1 is not HER2+ and you feel that both of them need chemotherapy in that situation. If the chemotherapy is needed, I tend to give the ACT [doxorubicin, cyclophosphamide, paclitaxel] backbone.

Joyce O’Shaughnessy, MD: How do you think about the TRAIN-2 data, VK? It wasn’t the hugest trial in the world—maybe that’s something that gives people a little pause—but the randomization to preoperative, 6 cycles of TCHP vs the equivalent of AC-THP. The pathologic complete response rates were really good from both of them: 60%, 78%. Then the disease-free survival was superimposable; albeit not the biggest trial in the world, but what do you think about that trial?

Vijayakrishna Gadi, MD: You hit the nail on the head, which is that they are still small experiences in the realm of things. But it is really encouraging, this ability to get away from the anthracyclines. Long term, that should be our goal. There’s always going to be, as Claudine pointed out, patients whose circumstances are different, where you think you need to escalate in that direction and offer more with an anthracycline or what have you. Certainly, if you have started a taxane-based therapy and you are watching the tumor grow on you, then that shakes your confidence about relying on the taxane-based therapy.

There are always going to be some circumstances in the preoperative setting in which you’re watching the tumor and you may have to change course. But as a rule, I agree with everybody here. We’re migrating away from anthracyclines in this place, but we’ll see what the long-term survival data are, even though it’s the small experience that can also be informative over the long haul.

Joyce O’Shaughnessy, MD: Great. We’re going to come back. We’re going through APHINITY and the T-DM1, and we’re going to touch on neratinib too, which may be helpful for some patients. Thank you. That’s a good place for us to start.

Transcript Edited for Clarity