Systemtherapie des Magenkarzinoms im Stadium IV – aktuelle Entwicklungen

Systemic treatment of metastatic or unresectable gastric cancer, including esophagogastric junction adenocarcinoma, has developed since 2021, with several new agents approved in Europe.

This article presents the new substances approved by the European Medicines Agency (EMA) and the phase III studies relevant for their approval.

The biomarkers HER2, PD-L1, and DNA mismatch repair deficiency/microsatellite instability (MSI) must be analyzed to determine the most effective first-line treatment for gastric cancer. In the first-line setting, biologic targeted agents are used in combination with chemotherapy consisting of a fluoropyrimidine and a platinum derivative (most commonly oxaliplatin). The majority of tumors are HER2 negative and microsatellite stable (MSS). Pembrolizumab or nivolumab can be used in case of a PD-L1 combined positive score ≥ 1 or ≥ 5, respectively. Tumors that are HER2 positive and PD-L1 positive should be treated with the combination of trastuzumab, pembrolizumab, and chemotherapy. Treatment of MSI-high tumors should use a combination of a checkpoint inhibitor and chemotherapy, although the EMA first-line approval is based on the PD-L1 score and not the MSI-high status. In the second-line setting, trastuzumab deruxtecan is approved for HER2-positive tumors. Pembrolizumab as monotherapy is approved for second- or later-line treatment of MSI-high tumors that have progressed during previous systemic treatment not including a checkpoint inhibitor.