Treatment Options in HER2-Positive Metastatic Breast Cancer

Sara A. Hurvitz, MD: The treatment of HER2 [human epidermal growth factor receptor 2]-positive metastatic breast cancer has vastly improved in the past several decades. In the past, the outcomes 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 from recently collected data about 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 likely due to the fact that we have so many targeted therapies available. At last count, we had 8 HER2-targeted therapies for metastatic disease, thus providing multiple options for patients whose disease progresses after first-line therapy. Right now, in the second-line setting, we use trastuzumab emtansine, or T-DM1, the antibody-drug conjugate, in the second-line approach. But that may change in the near future as new studies are published that compare T-DM1 to other types of therapies. So, we may see that second-line position change in the coming years.

In the third-line setting and beyond, we still have a multitude of options available for patients.

One exciting option that has been recently approved in the last few years is trastuzumab deruxtecan, or T-DXd, another antibody-drug conjugate that has been studied in a single-arm phase 2 clinical trial. T-DXd demonstrated remarkable efficacy, with an objective response rate greater than 60%, and a median progression-free survival around 20 months, in very heavily pretreated disease. This included patients with a heavy disease burden, including visceral disease. The other agent that’s very exciting is tucatinib, in combination with capecitabine and trastuzumab. This agent is a HER2-selective tyrosine kinase inhibitor. It’s a pill formulation given with a capecitabine, a pill chemotherapy, in combination with trastuzumab. In a phase 3 clinical trial, it showed remarkable efficacy, not only for patients with visceral mets [metastases] and nonvisceral metastases, but for patients with brain metastases. So, we have these 2 options available. Many would say that these would be the top 2 options we would consider in the third-line setting, and maybe selecting between those 2 based on whether a patient needs a quick objective response, or whether the patient has brain metastases. Ultimately, most patients will go on to receive the agent they don’t receive in the third-line setting. They’ll receive the other agent in the fourth-line setting. It is an exciting time to have all of these agents available.

Transcript Edited for Clarity