The evolving immunotherapeutic landscape in advanced oesophagogastric cancer

Abstract

Improvements in median overall survival in the advanced oesophagogastric (OG) setting have plateaued, underlining the need for improved therapeutic approaches in this patient population. Immunotherapeutics are inducing unexpected durable responses in an expanding list of advanced disease indications. Although OG cancers have traditionally been considered to be more challenging to treat with immunotherapy than some other malignancies because of their variable tumour mutational burden and relative scarcity of infiltrating T cells, immune checkpoint inhibitor (ICPI) trials conducted over the last few years suggest there is an important role for these treatments. ICPI efficacy may be demonstrated in specific molecular subtypes of OG cancer. This review outlines the improvements in defining predictive biomarkers of responsiveness to ICPIs. Increasingly, identification of an expanding list of ICPI resistance mechanisms will drive biomarker-directed research. In addition, the specific rationale to combine ICPIs with chemotherapies, radiotherapies, targeted therapies and other novel immunotherapeutic drugs will be discussed.