[Antibody drug conjugates: Use and optimization in HER2-negative metastatic breast cancers (triple negative,...

The therapeutic management of metastatic breast cancers has benefited in the past few years from important progress linked to the development of new molecules, inhibiting poly adenosine diphosphate ribose polymerase (PARP), cyclin-dependent kinases (CDK4/6) or immune checkpoints. More recently, the development of antibody-drug conjugates (ADC) targeting tumor cells, allows for the delivery of cytotoxic agents, at low doses, while increasing their concentration in the tumoral microenvironment. Currently, two ADC are available for the management of HER2-negative metastatic breast cancers, sacituzumab govitecan and trastuzumab deruxtecan. However, these ADC still induce significant grade 3/4 adverse events in more than 40% of the cases. Here, a practical review of the characteristics of these 2 ADC is proposed, with their mode of action and formulation, posology and place in the treatment schedules of HER2-negative metastatic breast cancers. The major results of phase III clinical trials are summarized, and a special focus is made on the management of toxicities.