Trastuzumab Deruxtecan for HER2-Low Metastatic Breast Cancer: Practical Considerations for Medical Oncologists and Pathologists in Australia

Abstract

Trastuzumab deruxtecan (T-DXd) is a third-generation, HER2-targeting antibody-drug conjugate that has been shown to significantly prolong overall survival, compared with standard chemotherapy, when used to treat patients who have “HER2-low” (HER2 immunohistochemistry [IHC] score 1+; or HER2 IHC 2+ plus in situ hybridization-negative) unresectable or metastatic breast cancer and who have received prior chemotherapy in the metastatic setting or developed disease recurrence during, or within 6 months of completing, adjuvant chemotherapy. The broad aims of this paper are: (a) To draw attention to some of the challenges associated with identifying whether patients have HER2-low metastatic breast cancer (mBC), in an environment where healthcare professionals have previously only needed to determine whether mBC is HER2-positive and therefore likely to respond to traditional HER2-targeted therapies; and (b) to indicate, where possible, what might be done to help overcome specific challenges in this regard. Advice regarding the management of specific T-DXd-related side effects of interest, including interstitial lung disease and pneumonitis, left ventricular dysfunction and emesis, is also offered.