Treatment Sequencing Strategies in HER2+ MBC

Vijayakrishna Gadi, MD, PhD: I’ll hand it over to Neil. He’s going to walk us through some ideas.

Neil M. Iyengar, MD: Thank you, VK. Our next topic is focusing on the first- and second-line systemic therapy options for our patients with HER2 [human epidermal growth factor receptor 2]-positive metastatic breast cancer. We can certainly look to the guidelines in terms of assessing what those options are, but with all of the data that have recently come out, the algorithm for how we treat patients and the individual patient factors in terms of individualizing our care for our patients is shifting. Let me pose a few questions to my colleagues to discuss these matters in concrete details. What factors do you consider when selecting first- and second-line options? VK, let me start with you. What are the factors that you’re considering in the first- and second-line?

Vijayakrishna Gadi, MD, PhD: It will always start with asking the patient, “What do you want to do?” I might lay out the options. We have limited flexibility around what we do first. A lot of these patients will be either naїve or have had a treatment break from whenever they were previously exposed to trastuzumab [Herceptin] and pertuzumab [Perjeta], so I’m going to reach for those agents first.

The real controversy or discussion will be, “Do we give it with a taxane? Which taxane? Or do I just give it with endocrine therapy based on the PERTAIN trial that Mothaffar Rimawi and colleagues published a few years ago showing really good synergy with the endocrine therapy and these biologics in hormone receptor–positive/HER2-positive disease?” Those are some questions in the first line. It’s about what the patient saw before, what their preferences are now, and what’s reasonable. If the HP [trastuzumab/pertuzumab]–based therapies are off the table for some reason, I’m going to graduate some of those second-line ideas into the first-line.

Second-line is where it gets interesting. If you’re looking for pure oomph and demonstration of power, we’re going to talk about the DESTINY-Breast03 trial where we’re looking at [trastuzumab] deruxtecan [Enhertu] as opposed to T-DM1 [trastuzumab emtansine] in that setting, but it’s clearly a more toxic agent across the board. Most people would agree with that. And then for patients who may have brain metastases, reaching for a tucatinib [Tukysa]-based option makes a lot of sense. It’s coming down to those. Patients are changing themselves. They’re seeing trastuzumab emtansine in the adjuvant setting, but what’s the value of rechallenging with that? That’s a complete data-free zone at this time, so maybe I’m going to reach for a different agent. These are the types of questions I’m looking at.

I don’t put a lot of weight in regard to pure visceral vs pure metastatic into the other organs like the brain, etc. But that’s also a consideration, things like volume of disease and how quickly I need a response. Mylin, I’ll hand it off to you. I don’t know if you have some additional thoughts in this regard.

Mylin A. Torres, MD: Thanks, VK. I completely agree with everything you said. The only thing that I’d add is patients’ prior tolerance for the agents that you mentioned. If they saw it in the definitive setting, did they have a lot of GI [gastrointestinal] distress through any of that? And reaching for something in the second-line, if they get to that point, with tucatinib and capecitabine [Xeloda], that regimen can be highly toxic. That’s one thing that I would think about.

Transcript edited for clarity.