Hôpital Européen Georges Pompidou, APHP, Université de Paris, Service de gastroentérologie et oncologie digestive, 20 rue Leblanc, 75015 Paris
Metastatic gastric adenocarcinoma is a disease with a poor prognosis, with a survival at diagnosis not exceeding 12 months until recently. Limited to conventional cytotoxic chemotherapy protocols for a long time, the therapeutic arsenal has been expanded in recent years with the emergence of new molecules. In the first line, doublet or triplet chemotherapy with a platinum salt and a fluoropyrimidine remains the standard treatment. The combination of docetaxel, oxaliplatin and 5-FU (FLOT/TFOX) has recently become a new standard in perioperative setting and is currently being evaluated in a phase III study that could lead to changes in the strategy of care. As a second-line treatment, ramucirumab, an anti-angiogenic agent targeting VEGF receptor 2, has demonstrated its efficacy alone or in combination with paclitaxel, leading to an authorization by the French health authorities (but without reimbursement). Chemotherapy based on irinotecan or taxane can also be used in this setting. In third-line or more, oral chemotherapy with trifluridine-tipiracil has become a new standard of care in patients with good performance status. For patients with HER2 overexpression, trastuzumab remains the only targeted therapy that has demonstrated a survival benefit. Its interest has only been proven in first line-setting in combination with platinum-based chemotherapy. New molecules targeting HER2 such as trastuzumab-deruxtecan have shown promising results that need to be confirmed by larger studies. Immunotherapy compared to chemotherapy has shown unconvincing results, but recent communications have suggested that the combination of immunotherapy with first-line chemotherapy could provide a survival benefit in selected patients with an intratumoral over-expression of PD-L1. Full results from these phase III studies are expected shortly and may lead to changes in the strategy of care.