Systemic Therapy of Gastric Cancer-State of the Art and Future Perspectives

Abstract

Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy.

Keywords: Her2; chemotherapy; esophago-gastric junction cancer; gastric cancer; immunotherapy; neoadjuvant; perioperative.

Figure 1

Biomarkers to select treatment for patients with advanced gastric cancer. ALK, anaplastic lymphoma kinase; EBV, Epstein-Barr-Virus; EGFR, epidermal growth factor receptor; dMMR, deficient DNA mismatch repair; FGFR2b, fibroblast growth factor receptor 2b; fus, fusion; HER2, human epidermal growth factor receptors-2; MET, mesenchymal-epithelial transition factor; MSI-H, microsatellite instability-high; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PD-L1, programmed cell death 1; TMB, tumor mutational burden.

Figure 2

First-line treatment algorithm for patients with advanced gastric cancer. dMMR, deficient DNA mismatch repair; HER2, human epidermal growth factor receptos-2; MSI-H, microsatellite instability high; PD-L1, programmed cell death 1. Modified according to European Society for Medical Oncology Gastric Cancer Guidelines [10].