Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer

Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate approved in several countries, including the USA and those of the EU, for adults with unresectable or metastatic HER2-positive breast cancer who have previously received at least one prior anti-HER2-based regimen. In a pivotal phase 3 trial in this setting, intravenous trastuzumab deruxtecan demonstrated prolonged progression-free survival compared with trastuzumab emtansine (previously the recommended second-line therapy in this indication). Trastuzumab deruxtecan had a generally manageable safety and tolerability profile. Common treatment-related adverse events included haematological and gastrointestinal disorders. Interstitial lung disease (ILD)/pneumonitis is associated with a regulatory warning and requires careful monitoring. In conclusion, trastuzumab deruxtecan is a valuable new treatment option for HER2-positive breast cancer, having been shown to be effective with a generally manageable safety and tolerability profile in adults with unresectable or metastatic disease who have received one or more prior anti-HER2-based regimens. Human epidermal growth factor receptor 2 (HER2)-targeted therapies have improved HER2-positive breast cancer outcomes in recent years. Despite this, almost all patients will eventually experience disease progression (cancer growth or spread). Trastuzumab deruxtecan (Enhertu®) is an intravenously administered treatment that combines a drug that is toxic to cells and an antibody that targets it to HER2-expressing cells. It has been approved in several countries for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have previously received one or more anti-HER2-based therapies. In a pivotal clinical trial, trastuzumab deruxtecan showed longer survival without disease progression than trastuzumab emtansine (the previously recommended treatment after first disease progression). Trastuzumab deruxtecan had a generally manageable safety and tolerability profile. The most common classes of adverse events were blood and gastrointestinal disorders. Fatal events of interstitial lung disease (ILD)/pneumonitis have occurred with trastuzumab deruxtecan and patient monitoring is required. Trastuzumab deruxtecan is a valuable new option for patients with unresectable or metastatic HER2-positive breast cancer who have received at least one prior anti-HER2-based regimen.