S3126 Evaluating the Impact of Monoclonal Antibodies on Survival Outcomes in Advanced Gastric Cancer: A Systematic Review of RCTs

Introduction: Conventional therapies for gastric cancer, such as chemotherapy and radiation, offer limited survival benefits and are often associated with considerable toxicity. The emergence of monoclonal antibodies has introduced a targeted approach, enhancing anti-tumor effects while reducing collateral damage. They are designed to bind tumor-associated antigens, offering a personalized treatment. Clinical trials assessing these therapies commonly use overall survival (OS) and progression-free survival (PFS) as endpoints. OS measures time from treatment to death, while PFS reflects the time during which the disease does not progress. Methods: We conducted a systematic review following PRISMA guidelines. Searches were performed across PubMed, Google Scholar, Cochrane Library, PLOS One, Science Direct, and ClinicalTrials.gov for randomized controlled trials (RCTs) published between 2015 and May 2025. Search terms included combinations of “gastric cancer”, “monoclonal antibodies”, and “antineoplastic agents”. Studies were included if they reported OS and PFS outcomes of monoclonal antibodies. Four RCTs met the inclusion criteria. Results: In Boku, et al. (2021), nivolumab demonstrated a significant OS benefit over placebo (5.3 vs 4.1 months) and a modest PFS benefit (1.61 vs 1.45 months). In Kong, et al (2024), inetetamab improved PFS compared to trastuzumab (8.5 vs 7.3 months; P = 0.046), but OS (15.4 vs 14.3 months) was not significantly different. Kang, et al (2024), reported that bemarituzumab plus combination folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin significantly improved both PFS (12.9 vs 8.2 months) and OS (24.7 vs 12.9 months) compared to placebo. In Qin, et al. (2025), pembrolizumab plus chemotherapy led to improved OS (15.9 vs 12.2 months) and PFS (8.1 vs 5.7 months) versus placebo plus chemotherapy. Conclusion: The integration of monoclonal antibodies and immune checkpoint inhibitors has transformed gastric cancer treatment. Trials show nivolumab improves OS modestly, with limited PFS benefit. Inetetamab significantly extends PFS over trastuzumab, though OS benefits remain unclear. Bemarituzumab combined with chemotherapy markedly improves both PFS and OS, highlighting the role of fibroblast growth factor receptor 2–targeted therapy. Pembrolizumab plus chemotherapy also significantly enhances survival outcomes. While traditional chemotherapy remains important, monoclonal antibodies are becoming essential for improving patient outcomes. Future studies should focus on refining combination strategies to maximize the benefits of these novel therapies.