Immunotherapy in Gastro-Oesophageal Cancer: Current Practice and the Future of Personalised Therapy

Initial studies of immune checkpoint inhibitors in biomarker unselected gastro-oesophageal cancer yielded limited improvement in survival. However, emerging data from recent clinical trials suggest immunotherapies may offer a meaningful clinical benefit within selected populations. Gastro-oesophageal cancer is a heterogeneous disease with respect to histopathological and molecular features; hypermutation and the biology of immune checkpoint pathways are key to appropriate selection of populations most likely to benefit from immune checkpoint inhibitors. Programmed death-ligand 1 expression, typically measured using the combined positive score, is an important biomarker in determining which patients may benefit from immunotherapy agents. However, combined positive score thresholds are not standardised across trials and the benefit in programmed death-ligand 1-negative cohorts is uncertain. Data suggest that patients with tumours with microsatellite instability, high tumour mutational burden and Epstein-Barr Virus positivity are more likely to benefit from immunotherapy, which may be of importance within programmed death-ligand 1-negative populations. Here, we describe the current evidence base for the use of checkpoint inhibitors in the treatment of advanced gastro-oesophageal cancer and adjuvant treatment of high-risk oesophageal cancer, as well as the ongoing studies of immunotherapy in the treatment of patients with gastro-oesophageal cancers across an increasing range of clinical settings.

Automated summary

Initial studies have shown limited improvement in survival for immune checkpoint inhibitors in unselected gastro-oesophageal cancer. However, recent clinical trials suggest that immunotherapies may offer significant clinical benefit in certain populations. The heterogeneity of gastro-oesophageal cancer in terms of histopathological and molecular features makes it important to identify the populations most likely to benefit from immune checkpoint inhibitors. Programmed death-ligand 1 expression is an important biomarker, but its threshold for determining benefits varies across trials. Patients with certain characteristics, such as microsatellite instability, high tumour mutational burden, and Epstein-Barr Virus positivity, are more likely to benefit from immunotherapy even in programmed death-ligand 1-negative populations.