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.