The current status of immunotherapy and future horizon in the treatment of metastatic and locally advanced gastroesophageal adenocarcinoma.

Introduction: Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field.

Areas covered: This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting. We also introduce ongoing clinical trials to address the current challenging issues in clinical practice.

Expert opinion: In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type. Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients. We hope that CLDN18.2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T, and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.