ISY10-1 - Novel approaches to treat gastric cancer in Europe

Abstract

A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification in clinical research. Anti-HER2 treatment which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery. However, resistance mechanisms for HER2 directed treatment are poorly understood and optimal patient selection remains challenging. Trastuzumab is currently the only approved anti-HER2-directed treatment. Other anti-HER2 drugs like lapatinib and TDM-1 were not effective. Results from the JACOB trial investigating the combination of trastuzumab and pertuzumab in first-line metastatic gastric cancer are awaited. Targeting angiogenesis is a novel concept in the management of advanced gastric cancer. Ramucirumab has prolonged survival in the second-line either as a monotherapy or in combination with paclitaxel. However, biomarkers for selecting patients who benefit from anti-angiogenic treatment are still lacking. First-line results of ramucirumab in combination with cisplatin and 5-FU chemotherapy from the RAINFALL study are awaited. Immune checkpoint blockade and inhibition of cancer stemness targets are two emerging directions for the medical treatment of gastric cancer. Large-scale international phase III studies are ongoing. Beyond that, preliminary European phase-2 results about targeted treatment against CLAUDIN 18.2, a tight junction protein with overexpression in gastric cancer, were promising and will most probably lead to international phase-3 investigation. In summary, promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment.