Rapidly Evolving Treatment Landscape for Metastatic Esophagogastric Carcinoma: Review of Recent Data

Esophagogastric cancer (EGC) is a heterogeneous group of malignancies that collectively represent the 2nd leading cause of cancer deaths worldwide. While surgery in combination with chemotherapy and/or radiation therapy represents the primary curative treatment for early stage disease, survival outcomes for the majority of patients with later-stage disease remain poor. Cytotoxic chemotherapy with platinum doublets such as 5-FU/leucovorin/oxaliplatin is the mainstay of treatment with incremental benefits provided by targeted therapy (trastuzumab, trastuzumab deruxtecan, ramucirumab) and immunotherapy (pembrolizumab, nivolumab). In this article, we provide an updated review and perspectives on the management of advanced EGC. We examine the distinct epidemiological, etiological and molecular features of each disease entity comprising EGC. After reviewing the critical studies that established conventional systemic cytotoxic and targeted therapeutics, we elaborate on recent promising and complex data with immune checkpoint inhibition focusing on implications of tumor histology and PD-L1 expression in the tumor microenvironment. We also highlight novel diagnostic and therapeutic strategies to build on these recent advances.