Fourth-line Trastuzumab deruxtecan in HER2-positive metastatic gastric cancer

Abstract

Gastric cancer (GC) is one of the most aggressive and unfavorably ongoing malignant neoplasms, occupying the fifth and fourth places in the structure of oncological morbidity and mortality, respectively. Overexpression of the human epidermal growth factor receptor 2 (HER2-neu) is detected in about 20% of patients with advanced GC, which made it possible to successfully use trastuzumab in combination with chemotherapy (CT) in this cohort of patients. The development of resistance to trastuzumab is a serious problem that requires research and development of new therapy targeted to blockHER2-neu. Trastuzumab deruxtecan is an antibody–drug conjugate consisting of an antibody to the HER2-neu receptor and a topoisomerase inhibitor linked by a cleavable tetrapeptide-based linker. The drug has proven its effectiveness as a monotherapy for the treatment of patients with metastatic or locally advanced HER2-positive gastric adenocarcinoma or cardio esophageal junction in the 2nd and subsequent lines of treatment. In the above clinical case a 57-year-old patient with CEС adenocarcinoma with metastatic liver damage, distant lymphnodes and the presence of HER2-neu overexpression is presented. After the standard first-line drug treatment according to the XELOX scheme with trastuzumab, the patient underwent surgical treatment followed by postoperative chemotherapy according to the FOLFOX scheme in combination with trastuzumab. Given the negative dynamics, the next step was 3 injections of nivolumab immunotherapy, which eventually led to the development of autoimmune hepatitis and rapid progression of the disease. Almost the last hope for the patient was the introduction of trastuzumab deruxtecan, which allowed for an objective response, as well as an improvement in the patient’s clinical condition, which led to the achievement of the longest possible progression-free survival (PFS).