Side Effects, Quality of Life Important to Consider in Breast Cancer Subset

Patients receiving Enhertu (fam-trastuzumab deruxtecan-nxki) for HER2-positive metastatic breast cancer showed “remarkable” outcomes, although it may have different side effects than standard of care treatments, Dr. Nancy Lin explained to CURE® at the 2024 ESMO Congress.

Lin is a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston.

LEARN MORE: Enhertu Demonstrates Overall, Intracranial Activity in HER2-Positive Breast Cancer

Lin sat down with CURE® at the 2024 ESMO Congress to discuss how Enhertu compares with standard of care for patients with HER2-positive metastatic breast cancer and how Enhertu may be tailored for patients’ specific needs and characteristics.

Transcript:

[Enhertu] showed really high levels of intracranial efficacy. I think that what was very notable was that in patients with previously untreated brain metastases, the response rate was 82% which I think is really remarkable. The median [progression-free survival (PFS; time patients live without disease worsening)] in the brain [metastases] cohort was over 17 months, again, remarkable. And the 12-month overall survival was over 90%.

There are obviously differences in the safety profile between [Enhertu] and the regimen that we often think of when we think about treating patients with HER2-positive brain [metastases], and that is the regimen of [Tukysa] (tucatinib), [Xeloda] (capecitabine) and Herceptin (trastuzumab). That regimen also produces CNS responses, [which] was about 50% in that study, the median PFS there was just over seven months. But there are differences in the safety profile as well. So for [Enhertu], there's more nausea and vomiting, which is very well controlled with appropriate antiemetic regimens. But there's also the risk of [interstitial lung disease] that needs to be watched for very carefully. With the [Herceptin, Tukysa and Xeloda] regimen, we see more diarrhea and hand-foot symptoms, primarily related to the [Xeloda].

So I think that what we're seeing here is that we're seeing multiple active options for patients, both with and without brain metastases. And the reality is that most patients will not be cured with one or more of these regimens, and they will actually go through sequential regimens. It's really more a matter of sequence than a matter of either or, in my opinion, but the side effect profiles are different.

When we counsel patients about what choices they might want to consider. We're going to be thinking about efficacy end points [end goals]. We're also going to be thinking about toxicity end points. And so for patients who don't want to lose their hair, perhaps [Tukysa, Xeloda and Herceptin] might be a preferable initial option. For patients who don't want to deal with the complications of oral therapies that they have to keep track of at home and prefer to come in once every three weeks for an IV therapy, the [Enhertu] may be preferable and for patients who have, for example, co-existing liver metastases, where we've seen that [Enhertu] has superior activity to the previous second-line standard of Kadcyla (ado-trastuzumab emtansine), I think many patients in that situation might elect [Enhertu].

This transcript has been edited for clarity and conciseness.

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