Treatment Options in HER2+ Metastatic Breast Cancer

Mark Pegram, MD: Hello, and thank you for joining this Targeted Oncology™ presentation entitled “Expanding Options for Relapsed/Refractory HER2-Positive Metastatic Breast Cancer.”

In recent years, as treatment of HER2 [human epidermal growth factor receptor 2]–positive breast cancer has improved and patients live longer, some will experience metastatic recurrence after treatment with frontline HER2-directed therapies. Today we are going to talk about the expanding role of recently FDA-approved novel options for these patients.

I am Dr Mark Pegram, the Susy Yuan-Huey Hung Professor of Medical Oncology, an associate director for clinical research, and an associate dean for clinical research quality at the Stanford School of Medicine in Stanford, California. Joining me today is Dr Julie Gralow, the Jill Bennett Endowed Professor of Breast Medical Oncology at the University of Washington School of Medicine in Seattle, Washington, and the clinical director of breast medical oncology at the Seattle Cancer Care Alliance. Julie, welcome.

Julie R. Gralow, MD: Thanks, Mark. Looking forward to a great discussion.

Mark Pegram, MD: Thank you so much for joining us. Let’s begin, shall we? I’d like to begin, Julie, with a talk about the likelihood that a patient—let’s say, who’s finished all her HER2-targeted neoadjuvant or adjuvant therapy or even extended adjuvant therapy—in this day and age, will develop a metastatic recurrence.

Julie R. Gralow, MD: Well, Mark, I think you and I both started our careers before we had HER2-targeted therapy, so we’ve seen a major change, a major improvement in the survival of early stage HER2-positive breast cancer over the years. When we added trastuzumab to chemotherapy, we saw a dramatic reduction in recurrences and deaths. In looking at the 10-year follow-up for overall survival from the combined NSABP B31 trial with the NCCTG-N9831 trial, at 10 years about 10% of patients in the trastuzumab arm had died of breast cancer. That was a node-positive group, as you’ll recall, and everybody in that group got chemotherapy with trastuzumab.

That’s not our standard of care anymore, and it was great that 90% were still alive at 10 years compared with what it would have been without trastuzumab. But now we’ve got data on the benefit of adding pertuzumab, at least in a node-positive population. The benefit of using response to preoperative chemotherapy to decide what to give postoperatively, such as T-DM1 [trastuzumab emtansine] with residual disease, we’ve got the data from the ExteNET trial with the neratinib following the completion of trastuzumab.

Of course, in our small node-negative patients, we’ve got great data from what we call the APT trial, the adjuvant paclitaxel trastuzumab trial, where we saw recently reported 7-year follow-up for node-negative, up to 3 cm, HER2-positive breast cancer. Where for just giving paclitaxel and trastuzumab alone, we saw a disease-free survival of 93% at 7 years but only 1% of the patients in that trial actually had a distant recurrence. Of the approximately 6% who had a recurrence or death, locoregional recurrence and contralateral recurrence accounted for about 3% of that 6%. Distant recurrence accounted for about 1% of the 6%, and deaths that weren’t related to breast cancer accounted for 2%. We also know that all HER2-positive breast cancer isn’t the same. We get different responses with the ER [estrogen receptor]–positive and the ER-negative. We have different regimens and different outcomes in the node-positive and the node-negative groups as well.

Mark Pegram, MD: Let’s talk for a minute about first-line regimens for HER2-positive metastatic breast cancer. What would you consider in 2020 to be the gold standard in terms of first-line treatment for metastatic disease?

Julie R. Gralow, MD: That’s shifting now that more patients are receiving pertuzumab, even T-DM1 [trastuzumab emtansine] and neratinib in the early line setting. We have to take into account what the patient did receive in the adjuvant setting and what the disease-free survival interval was from completing that therapy. We’ve used the CLEOPATRA trial regimen with taxane and trastuzumab and pertuzumab as our standard first-line regimen. That was a powerful study from combined HER2 antibodies with the taxane. But now that more and more patients have received pertuzumab, even T-DM1 [trastuzumab emtansine] in the adjuvant setting, I’m not sure that data are quite as applicable. We have to look at what the patient has received. We have to look at how long they were disease-free. And the good news is we’ve got 7 FDA-approved agents for treating metastatic breast cancer right now.

Mark Pegram, MD: What site of metastasis in particular is the most challenging for you, Julie?

Julie R. Gralow, MD: Brain mets [metastases] of course are a devastating relapse, and we actually see those frequently because in part, we do a good job of controlling the disease below the neck with our antibodies, our big molecules. But in an intact blood-brain barrier, they don’t necessarily penetrate so well. We do see more brain mets as a site of first recurrence or a site of an eventual recurrence in our HER2 population, in part because we’re doing such a good job of controlling the disease in the liver, lungs, and other sites, that the patients are living longer and have more time to develop the brain mets, sadly.

Transcript edited for clarity.