HER2+ Breast Cancer and the Role of Maintenance Therapies


Dr. Virginia Kaklamani discusses the role of maintenance therapies for HER2+ breast cancer.

Matthew Fowler: Let’s transition to patient-clinician discussions on the management of HER2-positive breast cancer. What is the role of maintenance therapy for this breast cancer?

Virginia Kaklamani, MD, DSc: In the metastatic setting, I look at this as being a marathon and not a sprint. These are patients who are going to live for a very long time, and it’s very important that we are careful with toxicities that they may have from our chemotherapeutic agents. Typically, our anti-HER2 therapy is easy to tolerate, but the chemotherapy that is administered with the anti-HER2 therapy may have potential adverse effects. In the first-line setting, I typically give around 6 months or so of the chemotherapy with the anti-HER2 therapy. If I see a nice response and the patient is doing well, I stop the chemotherapy and continue the anti-HER2 therapy as a maintenance therapy. On progression, I can reintroduce the chemotherapy, and then try to stop it again. Once we move into the second-line setting, we now have antibody-drug conjugates or tyrosine kinase inhibitors that take over our treatment. So, the maintenance therapy becomes a little less of an issue there. But in that first-line setting, I try to give as much maintenance therapy as possible with as little chemotherapy as possible.

Matthew Fowler: Very briefly, what are some recent developments in the treatment of relapsed or advanced HER2-positive breast cancer?

Virginia Kaklamani, MD, DSc: From the beginning of the pandemic, we had 3 or 4 different drugs approved in the metastatic setting in HER2-positive disease, so we’ve been lucky in the past couple of years. We have trastuzumab deruxtecan, which is an antibody-drug conjugate that has shown great efficacy in the second-line setting. We have tucatinib, a tyrosine kinase inhibitor, which in combination with capecitabine and trastuzumab has shown wonderful benefits, including for patients who have brain metastases. Neratinib also showed an improvement in outcomes compared to previous treatments such as lapatinib, so another active drug. Finally, we have margetuximab, which is another monoclonal antibody similar to trastuzumab in many ways, but it attracts the immune system a little more. This has shown good benefit when combined with chemotherapy in patients with metastatic HER2-positive breast cancer. We’re lucky to have a lot of options for our patients. We’re lucky enough to be struggling every day as to which option is the best, but these are good problems to have.

Transcript edited for clarity.

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