Treatment options in HER2-positive metastatic breast cancer

Sara A. Hurvitz, MD: The treatment of HER2 [human epidermal growth factor receptor 2]-metastatic positive breast cancer has improved considerably over the past decades. In the past, the results associated with this type of breast cancer were quite poor, and this subtype was associated with one of the worst prognoses. But now we know, thanks to recently collected data on the outcomes of patients newly diagnosed with metastatic breast cancer, that patients with HER2 + metastatic breast cancer may have the longest median overall survival. This is probably due to the fact that we have so many targeted therapies available. At last count, we had 8 targeted HER2 therapies for metastatic disease, providing multiple options for patients whose disease progresses after first-line treatment. Currently, as a second-line approach, we are using trastuzumab emtansine, or T-DM1, the antibody-drug conjugate, in the second-line approach. But that could change in the near future as new studies are published that compare T-DM1 to other types of therapy. So we may see this second line position change in the years to come.

Third line and beyond, we still have a plethora of options available for patients.

One interesting option that has been recently approved in recent years is trastuzumab deruxtecan, or T-DXd, another antibody-drug conjugate that has been studied in a phase 2 single-arm clinical trial. T-DXd has demonstrated remarkable efficacy, with an objective response rate of over 60%, and median progression-free survival around 20 months, in a very heavily pretreated disease. This included patients with a heavy burden of disease, including visceral disease. The other agent of great interest is tucatinib, in combination with capecitabine and trastuzumab. This agent is a selective tyrosine kinase inhibitor for HER2. This is a pill formulation given with a capecitabine, a chemotherapy pill, in combination with trastuzumab. In a phase 3 clinical trial, it showed remarkable efficacy, not only for patients with visceral disorders [metastases] and non-visceral metastases, but for patients with brain metastases. So, we have these 2 options available. Many would say these would be the 2 best options we would consider under the third line, and maybe choose between these 2 depending on whether a patient needs a quick objective response, or if the patient has brain metastases. Ultimately, most patients will continue to receive the agent they did not receive as part of the third line. They will get the other agent under the fourth line. It’s an exciting time to have all of these agents available.

Transcription edited for clarity