Next generation antibody-drug conjugates in the treatment of her2-positive metastatic breast cancer: literature review and clinical case demonstration.

Breast cancer, along with its high incidence, is characterized by an extreme degree of tumor heterogeneity, which is reflected in the presence of molecular genetic classification and treatment algorithms based on immunohistochemical and mutational characteristics of the tumor. The revolution in the treatment of the HER2-positive subtype occurred about 25 years ago, when the first targeted drug trastuzumab came to clinical practice. Currently, there are a large number of treatment options for this subtype of breast cancer, including the most advanced drugs such as monoclonal antibody + cytotoxic agent conjugates. Trastuzumab deruxtecan is a new generation antibody–drug conjugate that has been registered in Russia and other countries as the therapy of choice in 2 and subsequent treatment lines for metastatic HER2-positive breast cancer. The article presents randomized clinical trials that formed the basis of these indications, and a phase IIIb/IV study DESTINY-Breast12 demonstrating high intracranial activity of this drug. The clinical case illustrates the effectiveness of trastuzumab deruxtecan in a late line in a pretreated patient with multiple metastasis including brain, as well as the possibility of diagnosing and correcting a specific adverse event such as interstitial lung disease.