Considering Novel Therapy for HER2+ Metastatic Breast Cancer


A summary of sequencing therapy in the HER2+ metastatic breast cancer treatment paradigm followed by excitement for novel therapies under investigation.

Neil Iyengar, MD:
[This has been a] great discussion. I’ve enjoyed going through those cases with you. We’ll start to wrap up and summarize our discussion. We had a nice discussion about how the landscape for HER2 [human epidermal growth factor receptor 2]–positive disease has been changing. I’ll summarize by reiterating what we’ve heard. We still have the current standard of care in the first-line setting, with the bar set at CLEOPATRA with taxane, trastuzumab [Herceptin], and pertuzumab [Perjeta]. The second-line setting is where we’re starting to see the evolution of the treatment approach with trastuzumab deruxtecan [Enhertu] entering that second-line space based on DESTINY-Breast03. HER2CLIMB makes a case for using the tucatinib [Tukysa]–based regimen in the second-line setting as well. For our patients with active CNS [central nervous system] disease, I would use a tucatinib-based regimen in the second-line setting.

As we move into the third-line setting and beyond, we still have T-DM1 [trastuzumab emtansine], particularly for patients who may not have seen it in the adjuvant setting. Then we have trastuzumab deruxtecan, tucatinib, margetuximab [Margenza]–chemotherapy in later lines, neratinib [Nerlynx] and capecitabine [Xeloda] as we’ve discussed, and of course some of our traditional agents like lapatinib [Tykerb] and other chemotherapy combinations. Milana, is there anything coming down the pipeline? What are you excited about as we look forward to the future in terms of how the landscape may continue to change?

Milana Dolezal, MD, MSci: In the metastatic setting, I’ve put patients on the CLEOPATRA regimen plus immunotherapy, so that’s another evolving space certainly in the triple-negative setting. We have data with immunotherapy [based on the] KEYNOTE studies. The IMpassion studies were somewhat disappointing, but in terms of the HER2+ space, what’s the role of immunotherapy there? There’s a first-line study that I’ve put patients on, trying to answer that question.

I alluded to the COMPASS trials, and there are a few caveats to that. In lower-risk and older patients, it’s nice to have the neoadjuvant therapy, where the role of carboplatin is not as important as doing that type of adjuvant treatment in the neoadjuvant setting, especially for grade 2 and older patients. This de-escalation idea is something we’ve seen in the breast cancer world with the ADAPT trials and other non-HER2 trials, like COMPASS in the neoadjuvant setting.

We’re getting at this brain metastases prevention issue and the COMPASS adjuvant trial with the addition of tucatinib to T-DM1 [trastuzumab emtansine] in high-risk patients with no pathologic CR [complete response]. I’ve been putting patients on that trial as well. We’re optimizing therapies to the point where we hope these patients don’t become metastatic. But if they do, then we have other options and other strategies to deal with this and with HER2 disease as a chronic disease. That landscape has changed dramatically, so there’s a lot to be excited about.

Transcript edited for clarity.

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