Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

SIMPLE SUMMARY: Biomarker research for immunotherapy in gastroesophageal cancer has been rapidly developing in parallel with the growing use of immune checkpoint inhibitors. Although several biomarkers have been approved for use in the clinical setting they are imperfect in predicting responses. Several novel biomarkers are currently being studied and demonstrate potential for application in the clinical setting. Future research should determine the ability of immunotherapy biomarkers to predict response and synergy in combination therapy. ABSTRACT: Advanced gastroesophageal cancer (GEC) has a poor prognosis and limited treatment options. Immunotherapy including the anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab have been approved for use in various treatment settings in GEC. Additionally, frontline chemoimmunotherapy regimens have recently demonstrated promising efficacy in large phase III trials and have the potential to be added to the therapeutic armamentarium in the near future. There are currently several immunotherapy biomarkers that are validated for use in the clinical setting for GEC including programmed death ligand-1 (PD-L1) expression as well as the tumor agnostic biomarkers such as mismatch repair or microsatellite instability (MMR/MSI) and tumor mutational burden (TMB). However, apart from MMR/MSI, these biomarkers are imperfect because none are highly sensitive nor specific. Therefore, there is an unmet need for immunotherapy biomarker development. To this end, several biomarkers are currently being evaluated in ongoing trials with some showing promising predictive potential. Here, we summarize the landscape of immunotherapy predictive biomarkers that are currently being evaluated in GEC.