Role of Systemic Treatment for Advanced/Metastatic Gastric Carcinoma in the Third-Line Setting: A Bayesian Network Analysis

Background: Increasing evidences from phase II or III trials have proved that salvage systematic therapy, including chemotherapy, target therapy, or checkpoint inhibitor therapy can prolong survival in patients who do not succeed with second line therapy, yet there are no guidelines for the optimum third-line treatments. To compare the effectiveness and safety of current third-line therapies for metastatic Gastric Cancer (mGC), we conducted this network analysis. Methods: Literature up to Sep 30, 2019 were systematically searched and analyzed by a Bayesian fixed-effect model. Results: This study included seven randomized clinical trails which involved 2,655 patients. It turns out that for overall survival, nivolumab has the highest probability to be the optimal choice for overall survival (OS). For patients with no peritoneal metastases, the network meta-analysis showed that Nivolumab (HR:0.64; 95% CI: 0.48-0.85) and Trifluridine/tipiacil (HR:0.66; 95% CI: 0.51-0.86) were associated with significantly higher improvement in OS than placebo. However, patients with peritoneal metastases could not benefit from nivolumab, ramucirumab, or Trifluridine/tipiacil, when compared with a placebo. For progression-free survival, apatinib (850 mg) was the most likely candidate, followed by ramucirumab. Statistically, Apatinib (850 mg), Trifluridine/tipiacil, and SLC had higher incidences of high-grade adverse events (AEs) than placebo. Conclusion: Our findings demonstrate that nivolumab has the best balance between acceptability and effectiveness in the third line therapy for mGC.