Immunotherapy in metastatic oesophagogastric cancer: biomarker-based treatment selection

In this video, Prof Dr Eric Van Cutsem speaks with Prof Dr Markus Moehler about the evolving role of immunotherapy in metastatic oesophagogastric cancer, following Dr Moehler’s educational lecture at ESMO GI 2026 in Munich. Prof Dr Moehler emphasises that immune checkpoint inhibition has changed the treatment approach in advanced gastric and gastro-oesophageal junction cancer, with a subset of patients now achieving long-term survival. In his view, approximately 20% of patients may be alive at 3 years when immunotherapy is combined with FOLFOX or CAPOX/XELOX-based chemotherapy, although many patients still experience disease progression. 

The discussion focuses on first-line treatment selection in metastatic gastric adenocarcinoma. Prof Dr Moehler highlights the need to assess MSI/MMR, HER2, PD-L1 by CPS or TAP score, and CLDN18.2 at diagnosis. For HER2-positive disease, he refers to accumulating evidence supporting the combination of HER2-targeted therapy with immunotherapy, including data from KEYNOTE-811 and HERIZON-GEA-01 with zanidatamab. 

A substantial part of the interview addresses treatment selection in patients with CLDN18.2-positive disease, particularly because zolbetuximab cannot yet be routinely combined with an immune checkpoint inhibitor; only phase II data are currently available and a phase III trial is ongoing. Prof Dr Moehler states that zolbetuximab may be particularly relevant for patients with high CLDN18.2 expression and lower PD-L1 CPS levels. For patients with CPS ≥5, he considers immunotherapy a clear option, while for CPS ≥10 he would clearly include immunotherapy. In intermediate situations, such as CPS 7 with strong CLDN18.2 positivity, he emphasises that treatment choice should include discussion with the patient about expected benefit and toxicity. 

The interview also discusses practical toxicity management with zolbetuximab. Prof Dr Moehler notes that nausea and vomiting can usually be managed with adequate antiemetic prophylaxis, including dexamethasone, olanzapine and anxiolytic/supportive medication when appropriate. In most cases, he suggests that infusion prolongation is limited, although splitting zolbetuximab and chemotherapy across 2 days can be considered in selected patients, particularly younger or female patients. Overall, the conversation underlines the need for early comprehensive biomarker testing and individualised treatment decisions as immunotherapy, HER2-targeted therapy and CLDN18.2-directed therapy increasingly overlap in first-line care.