Preferences for Treating Relapsed HER2+ MBC

Vijayakrishna Gadi, MD, PhD: Hello, everyone. My name is VK Gadi, and welcome to this OncLive® Insights program titled “Updates in the Treatment of HER2+ Metastatic Breast Cancer.” I’m going to be leading today’s discussion along with 2 of my colleagues and friends, Dr Neil Iyengar and Dr Mylin Torres. Neil and Mylin, would you mind introducing yourselves, please?

Neil M. Iyengar, MD: Hi, I’m Dr Neil Iyengar. I’m a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.

Mylin A. Torres, MD: Hi, I’m Dr Mylin Torres. I’m a breast cancer radiation oncologist at Emory University in Atlanta, Georgia.

Vijayakrishna Gadi, MD, PhD: Thank you. Again, my name is VK Gadi. I’m a medical oncologist and the director of medical oncology at the University of Illinois Cancer Center. Let’s jump right into it. Over the last several weeks, we have done some Twitter-based polling on a couple of interesting cases and we’re going to look at some of those responses. Before we do that, why don’t we start with the cases?

The first case is a 60-year-old woman presenting with a 4.2 cm left breast mass, a T2, and 3 palpable axillary lymph nodes, so N1. Biopsy showed invasive ductal carcinoma, hormone receptor–negative, but positive 3+ for the HER2 [human epidermal growth factor receptor 2] receptor. Unfortunately, MRI of the brain also showed 3 lesions, the largest being 1.1 cm. She received 6 cycles of THP—Taxotere [docetaxel], Herceptin [trastuzumab], and Perjeta [pertuzumab]—followed by TP maintenance with just the trastuzumab and Perjeta. There was partial response in the breast mass and complete response in the brain lesions, but 22 months later, she had recurrence in 3 brain lesions, the largest being 0.8 cm.

We asked the question, “What’s the next best line of therapy?” and the answers were interesting. The first was trastuzumab deruxtecan [Enhertu] with 44%; 33% chose tucatinib [Tukysa]/capecitabine [Xeloda]/trastuzumab; 0% chose neratinib [Nerlynx]/capecitabine; and 22% chose trastuzumab emtansine, also known as T-DM1. With that in mind, what do you guys think of those responses? Mylin, I’ll start with you.

Mylin A. Torres, MD: I’m surprised that stereotactic radiosurgery [SRS] wasn’t one of the options for the next best line of therapy. In a patient like this, where they’ve had great responses systemically to THP and then TP, you may want to treat those active brain lesions before they become symptomatic, and then go on to systemic therapies. In this case, trastuzumab deruxtecan has very compelling data to support that approach at that point.

Vijayakrishna Gadi, MD, PhD: Fair point. Neil, what do you think?

Neil M. Iyengar, MD: I agree with Mylin’s point. Considering local therapy to the brain would be a reasonable option here. One of the silver linings about this particular case is that there are multiple options that we used to not have. I certainly think that local therapy and possibly continuing systemic therapy or even resuming the cytotoxic component of the systemic therapy is an option. But of the answer choices listed here, we now have data to support CNS [central nervous system] activity with all of these options.

My personal comfort level in terms of a person who has known CNS metastases is toward the tucatinib-based regimen because that’s where we have the most robust amount of data in terms of CNS response, objective response, progression-free survival, and overall survival in patients who have brain metastases. We saw some preliminary data at ESMO [European Society for Medical Oncology Congress 2021] with regard to the CNS activity of trastuzumab deruxtecan, so I’m watching that story very closely. But my preference for this particular case would be the tucatinib-based regimen.

Vijayakrishna Gadi, MD, PhD: Thanks, Neil and Mylin. I agree with both of you. SRS seems like a very reasonable first thing to reach for, but let’s say this patient couldn’t get it for whatever reason. I also like B as an answer, particularly based on the survivability data that we just discussed. But patients with this scenario were enrolled on that trial with intentionality. We know that this is a group that was captured. We know that there are response rates in this category of patients with this combination of agents as well. For some reason, you couldn’t do local control for whatever the explanation. B makes the most sense out of the choices given. We’ll talk about the TUXEDO trial a little later in this seminar. Neil, that’s the trial you mentioned regarding deruxtecan.

Transcript edited for clarity.