Case 2 – Lack of response to trastuzumab in a patient with metastatic gastric cancer progressing after extended response to MET inhibitor therapy

Abstract

In patients with advanced gastric cancer with high expression of HER2 protein, the addition of trastuzumab to chemotherapy significantly improves overall survival compared with chemotherapy alone in the first line setting. However, there are no data on anti-HER2 therapies beyond disease progression after first-line therapy. In many types of cancers, including gastric cancer, dysregulation of the receptor tyrosine kinase MET may lead to a more aggressive cancer phenotype and may be a negative prognostic indicator. Therapeutic targeting of MET/hepatocyte growth factor (HGF) signalling has used monoclonal antibodies and smallmolecule tyrosine kinase inhibitors (TKIs) against the MET receptor and its ligand, with several drugs in latephase clinical trials, including onartuzumab. Onartuzumab is a humanized monovalent monoclonal antibody directed against the hepatocyte growth factor receptor (c-Met). In advanced gastric cancer, the addition of onartuzumab to a standard chemotherapy regimen with oxaliplatin and fluoropyrimidine did not improve efficacy in gastric cancer patients in the overall study population or in those selected for positive MET status by immunohistochemistry. In this clinical case we observed a good clinical response to FOLFOX plus onartuzumab in a young patient with MET-positive gastric cancer. However, therapy with cisplatin, 5-fluorouracil and trastuzumab used after progression did not provide a benefit. This case report therefore highlights the importance of always fully identifying potential therapeutic targets in our patients in order to offer more personalized therapies. A correct molecular analysis is very important in deciding the therapeutic sequences in the metastatic setting.