Lisa A. Carey, MD, FASCO: Hello, and welcome to this OncLive® Peer Exchange® titled “State-of-the-Art Care for HER2-Positive Metastatic Breast Cancer.” I’m Dr Lisa Carey. Joining me in this discussion are my colleagues Dr V.K. Gadi from the University of Illinois Cancer Center in Chicago, Illinois, Dr Reshma Mahtani from Sylvester Comprehensive Cancer Center in Miami, Florida, and Dr Lee Schwartzberg from the West Cancer Center & Research Institute in Memphis, Tennessee. Today we’re going to highlight several topics pertaining to the systemic treatment for HER2+ metastatic breast cancer and the impact of recent clinical trial data on clinical decision-making. In addition, we’re going to talk about some of the data from ASCO [American Society of Clinical Oncology Annual Meeting] 2021. Let’s get started.

The first series of questions that I’m going to pose to you guys—Lee, Reshma, and V.K.—relate to how we approach this now. What are the tools in the toolbox that you use in a clinical scenario? As we think about the first- and second-line systemic options that are FDA approved, and according to recommendations, what do we think about the historical frontline standards? How do you guys approach first- and second-line treatment? How do you consider hormone receptor status? Reshma, I’m going to ask you to kick it off.

Reshma Mahtani, DO: Thanks, Lisa. We’ve made dramatic progress in the treatment of HER2+ metastatic breast cancer, and we’re fortunate to be having this discussion on how to sequence many of these therapies. In the first-line setting, firmly established at this point, is the CLEOPATRA regimen, which is the taxane and dual-antibody therapy with trastuzumab [Herceptin] and pertuzumab [Perjeta]. We’ve seen 8-year landmark overall survival data presented, which prove we have a 16-month improvement in overall survival, with the use of dual-antibody therapy and taxane as a first-line treatment. This has become firmly established as our first-line treatment.

In patients with hormone receptor–positive, HER2+ disease, many physicians are monitoring an induction period of a few cycles—up to 6 cycles of taxane-based therapy—stopping the taxane, and then administer maintenance endocrine therapy with the dual-antibody therapy. I’ve routinely done this in my practice as well.

In terms of second-line therapy, a firmly established treatment is the T-DM1 [trastuzumab emtansine] regimen that was based on the EMILIA trial. Looking at this agent vs lapatinib [Tykerb] and capecitabine [Xeloda], shows an improvement in progression-free and overall survival. Fortunately, as I mentioned earlier, we’ve had the approval of new therapies—including the tucatinib regimen: tucatinib [Tukysa], trastuzumab, and capecitabine—based on the HER2CLIMB study, which has led to an indication to consider this therapy as second line and beyond. I’m sure we’ll have a robust discussion about where we might utilize this treatment in the second-line. But T-DM1 [trastuzumab emtansine], for now, has been routinely used in that setting.

Lisa A. Carey, MD, FASCO: Lee, any additional comments on that? V.K.?

Lee S. Schwartzberg, MD, FACP: As Reshma said, we have an embarrassment of riches, which is wonderful for our patients. As everything changes, including adjuvant therapy, it becomes a little more difficult to incorporate the trial data—based on what we were doing before—in our patients. For example, most of our patients in the early stage of HER2+ breast cancer are getting neoadjuvant therapy, and if they have less than a PCR [polymerase chain reaction], they tend to get T-DM1 [trastuzumab emtansine]—based on the strong results of improvement. We have a setting in which the treatment that patients have had before, may have an impact on what we use now. In the CLEOPATRA trial, it’s worth remembering that about 20% of patients had exposure to pertuzumab, and none to T-DM1 [trastuzumab emtansine]. So that regimen, which is so outstanding in terms of 5-year survival median, doesn’t necessarily reflect what’s happening as patients relapse. But it’s great for de novo patients, for sure. We have to rethink what we might use in the first-line setting and remember that when patients relapse, these are complex decisions.

Vijayakrishna Gadi, MD, PhD: On the 1 hand, it seems like an embarrassment of riches, which I agree with. But because of what Lee just pointed out, there’s an unmet need that we didn’t have before because all our patients in this metastatic setting—many of them anyway—have seen a lot of therapies. We need to keep at it.

Lisa A. Carey, MD, FASC: I totally agree. We’re going to talk about what Reshma alluded to a little later, which is how you differentiate hormone receptor–negative HER2+ breast cancer first-line therapy and hormone receptor–positive HER2+ breast cancer first-line therapy, because that’s an emerging arena.

Transcript Edited for Clarity