On the basis of the international multi-center phase III Trastuzumab for Gastric Cancer (ToGA) trial, trastuzumab improved survival in patients with human epidermal growth factor receptor (HER)-2 positive advanced or metastatic gastric or gastro-oesophageal junction cancer compared with chemotherapy alone and indicated for this population in EU, United States, and Japan. Trastuzumab has been standard of care in the treatment of HER-2 early and advanced breast cancer over a decade and is also expected as the same treatment strategy for gastric cancer. Other HER-2-targeted drug, lapatinib is also evaluated in gastric cancer with randomized phase III trials which are named LOGiC (CapeOx ± lapatinib) for first-line and TYTAN (weekly paclitaxel ± lapatinib) for second-line treatment. These results will lead to the firm concept of HER-2-positive gastric cancer.
Looking through in clinical development for patients with HER2-positive breast cancer, trastuzumab-DM1 (T-DM1), a conjugate of trastuzumab with DM1 (a derivate of maytansine), and pertuzumab, binds to the HER2 ECD but at a different site to trastuzumab, and is able to inhibit ligand-induced dimerization of HER2 with its receptor partners showed promising results. Positive data from the CLEOPATRA study (Docetaxel − trastuzumab ± pertuzumab in which patients with metastatic breast cancer were randomized) suggest that these agents are also considered for clinical development in the future treatment of gastric cancer.