Side Effects to Monitor During HER2-Positive Breast Cancer Treatment

There are side effects that patients need to be aware of during every line of treatment for HER2-positive metastatic breast cancer, as one expert explained.

Dr. Alyssa Beck of the Division of Hematology/Oncology at UC San Diego Comprehensive Breast Health Center discussed the treatment landscape and accompanying side effects during a discussion on HER2-positive metastatic breast cancer as part of the CURE® Educated Patient® Metastatic Breast Cancer Summit.

“We typically continue a [treatment] regimen until it stops being effective or if it's not tolerated,” Beck said. “In general, scans are done every three-ish months, although it depends on visits, labs, how someone's feeling, etc. And we can sometimes even extend those if someone's doing well for a while. And then, really, really importantly, is meeting patients where they're at balancing quality of life and side effects. For instance, if a patient is older and won’t tolerate chemotherapy, we can start out with more targeted agents, and there are trials to show that that can be quite beneficial and less toxic.”

Generally, Beck explained, first-line treatment (the first treatment patients receive for a disease) will entail the antibody Herceptin (trastuzumab), potentially paired with the antibody Perjeta (pertuzumab), and a chemotherapy, commonly docetaxel.

“Herceptin, how it works is it's an antibody that binds to the HER2 protein on the surface of HER2-positive breast cancer cells and it can slow and stop their growth,” Beck explained. “Perjeta is very similar, it just binds to a different spot.”

Perjeta is always given together with Herceptin, but Herceptin can be given alone, she noted.

“Some of the really important side effects for these [treatments] are [effects that can require] heart monitoring because these drugs can impact how the heart squeezes,” Beck said. “So we get echocardiograms, usually every three months. [There is also] diarrhea, more with the Perjeta than the Herceptin, and infusion reaction. So, we monitor patients closely in the infusion center. The infusion reactions can be headaches or fevers, chills, [and are] usually light, mild. In the very rare instance, it can be more [severe, and] we watch them closely.”

Moving to the second line, Beck explained the science behind Enhertu (trastuzumab deruxtecan).

“It’s Herceptin, so that same [antibody] bound to chemotherapy drugs, so we call this an antibody-drug conjugate,” she said. “Typically, [it’s] less toxic than chemotherapy [but] has other side effects. But it can also be effective on breast cancer that has spread to the brain and actually not just the brain but leptomeningeal disease.” Leptomeningeal disease is when cancer spreads to the meninges, the thin layer of tissue covering the brain and spinal cord, according to the National Cancer Institute.
Side effects, Beck explained, can be gastrointestinal or can include low blood counts as well as hair thinning or loss. “We have to monitor the heart, again,” she noted, “because [Enhertu] has Herceptin in it.”

Compared to another antibody-drug conjugate, Kadcyla (ado-trastuzumab emtansine), Enhertu has been shown, Beck said, to result in superior progression-free survival (the time a patient lives without their disease spreading or worsening) and overall survival (the time a patient lives regardless of disease status). However, Beck also noted that nausea and hair loss were less common with Kadcyla than with Enhertu, though both had low rates of severe nausea and vomiting and complete hair loss. Other side effects of Kadcyla include low blood counts and increased liver enzymes.

“Really importantly with Enhertu and also Kadcyla, but mostly Enhertu, is something called pneumonitis, which is irritation in the lungs,” Beck said. “And it can be very severe, although those were quite, quite rare to be very severe, but even [with] grade one or grade two [mild or moderate side effects], we're very careful.”

“We always ask people at their visits [about] cough, shortness of breath [and] any change in your breathing,” Beck said, noting that in such cases, “typically, we’ll hold the medication and treat with steroids, and then resuming depends on how severe it was, discussion with the patient and things like that.”

The third line of treatment, Beck explained, includes Herceptin as well as the chemotherapy pill Xeloda (capecitabine), which has side effects including nausea, diarrhea, low blood counts and hand and foot rash, as well as Tukysa (tucatinib) — described by Beck as “a small molecule inhibitor of HER2, so another kind of targeted treatment and [one that], again, binds to the HER2 receptor … on the cell surface, it blocks signals [in order] to stop the cancer cell from growing.” Side effects of Tukysa include nausea, diarrhea, vomiting, rash and, rarely, liver problems, she said.

Things are less clear in the fourth line of treatment and beyond, Beck said, with options including newer antibodies such as Margenza (margetuximab-cmkb), which has side effects such as infusion reactions and the need for heart monitoring.

Editor's note: This program was made possible with support from Daiichi Sankyo Inc.

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