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

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.