The Present and Future of Neoadjuvant and Adjuvant Therapy for Locally Advanced Gastric Cancer

SIMPLE SUMMARY: Gastric cancer is a deadly disease with worldwide prevalence that is often diagnosed at late stages. About two-thirds of patients in Western countries will present with locally advanced gastric cancer (LAGC). When patients are diagnosed with LAGC, they frequently undergo surgery and perioperative chemotherapy. However, the most effective multimodality treatment regimen for LAGC has yet to be determined. In aiming to improve outcomes, current trials are examining immunotherapies and targeted therapies based on a growing understanding of the unique molecular characteristics and subtypes of LAGC. This review summarizes current and future medical therapies for LAGC. ABSTRACT: Gastric cancer is a highly prevalent and lethal disease worldwide. Given the insidious nature of the presenting symptoms, patients are frequently diagnosed with advanced, unresectable disease. However, many patients will present with locally advanced gastric cancer (LAGC), which is often defined as the primary tumor extending beyond the muscularis propria (cT3-T4) or having nodal metastases (cN+) disease and without distant metastases (cM0). LAGC is typically treated with surgical resection and perioperative chemotherapy. The treatment of LAGC remains a challenge, given the heterogeneity of this disease, and the optimal multimodal treatment regimen may be different for different LAGC subtypes. However, many promising treatments are on the horizon based on knowledge of molecular subtypes and key biomarkers of LAGC, such as microsatellite instability, HER2, Claudin 18.2, FGFR2, and PD-L1. This review will expand upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC and explore the ongoing and future clinical trials for novel therapies, with information obtained from searches in PubMed and ClinicalTrials.gov.