First-Line Systemic Therapy Outcomes in Western Population with Locally Advanced and Metastatic Gastric Cancer—A Systematic Review

Globally, gastric cancer is a major cause of cancer mortality, with a 5-year survival rate of 32% for locally advanced and metastatic gastric cancer (A/MCG). This systematic literature review summarized the clinical, safety, and humanistic outcomes associated with systemic regimens administered as a first-line therapy for A/MGC. The search included articles published in English in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and the American Society of Clinical Oncology meeting library, from inception to April 2022. Phase II and III randomized controlled trials (RCTs) conducted among western populations diagnosed with stage III and IV A/MGC were included. Two investigators independently reviewed the studies, conducted data extraction, and assessed risk of bias in accordance with PRISMA guidelines. Twenty-four randomized controlled trials totaling 8705 patients were included. Median overall survival ranged from 5.0 to 13.1 months, median progression-free survival ranged from 2.0 to 7.7 months, and objective response ranged from 13.0 to 64.1%. Two studies reported high quality-of-life outcomes. Grade 3 and 4 adverse events were reported in most studies. This review provides a comprehensive overview of first-line systemic therapy outcomes in western populations with A/MGC. With the evolving treatment landscape of A/MGC, an improvement in clinical outcomes can be seen in recently published RCTs with immunotherapies. The potential of new targeted treatments and immunotherapies may present more favorable forthcoming options for treating A/MGC.