New developments and standard of care in the management of advanced gastric cancer

Advanced gastric adenocarcinoma is a common disease with a poor prognosis whose treatment has for decades been based on cytotoxic chemotherapy, including platinum salts in first-line, and taxane or irinotecan in second or later line. Recent years have seen the emergence of new drugs that have improved patient survival, such as trastuzumab in first-line for HER2-positive tumors, ramucirumab alone or in combination with paclitaxel in second-line, and trifluridine-tipiracil beyond the second-line treatment. More recently, two monoclonal anti-bodies have demonstrated their efficacy in combination with oxaliplatin-based first-line chemotherapy, nivo-lumab (anti-PD1) for PD-L1 CPS >= 5 tumors, and zolbetuximab for tumors overexpressing Claudin 18.2. In addition, regorafenib has been also showed effective in phase 3 trial for heavily pretreated patients. Based on phase 2 studies, trastuzumab-deruxtecan was approved in 2022 by the EMA for HER2-positive pretreated pa-tients. This agent is currently evaluated in phase 3 study (DESTINY-Gastric04 trial), as are several other anti-HER2 (zanidatamab, margetuximab, tucatinib), immune checkpoint inhibitors, or targeted therapies (anti-FGFR2b).

Automated summary

Advanced gastric adenocarcinoma is a disease with poor prognosis. In recent years, new drugs, such as trastuzumab for HER2-positive tumors, ramucirumab alone or in combination with paclitaxel, and trifluridine-tipiracil, have improved patient survival. Other drugs, including monoclonal antibodies and targeted therapies, are also being evaluated.