A third ADC, trastuzumab deruxtecan, targets the HER2 protein, like trastuzumab emtansine, but with a different cytotoxic payload. It consists of trastuzumab linked to deruxtecan, whose cytotoxicity inhibits DNA replication. It is approved for the treatment of HER2+ mBC. Its FDA approval was based on the results of the DESTINY-Breast04 phase 3 clinical trial, which demonstrated that treatment with trastuzumab deruxtecan, when compared with standard-of-care chemotherapy, doubles progression-free survival among patients with mBC that expresses low levels of HER2. The median OS for patients in the HR+ group who received trastuzumab deruxtecan was 23.9 months vs 17.5 months for those who received chemotherapy. In the hormone receptor-negative (HR−) group, the median OS for those who took trastuzumab deruxtecan was 16.6 months vs 10.3 months for those treated with chemotherapy.
The emergence of ADCs have demonstrated promising advancements in the treatment of BC, particularly in patients with HER2+ or triple-negative disease. ADCs have given new hope to and prolonged life for patients living with pretreated HR+/HER2− mBC. ADCs also have the potential to provide a more effective and less toxic treatment option for patients with BC. However, further research is needed to fully understand their long-term effects and to develop new ADCs that target other types of BC.