Comparative efficacy and tolerability of target agents and immune checkpoint inhibitors in combination with chemotherapy as First-line treatment for advanced gastric cancer: A Bayesian network meta-analysis

Abstract Background The use of target agents and immune checkpoint inhibitors have changed the treatment landscape for AGC in the first-line setting. However, the crosswise comparison between each regimen is rare. Therefore, we estimated the efficacy and safety of targeted therapy or immunotherapy with chemotherapy in AGC patients as the first-line treatment; Method Included studies were divided into “unselected” or “selected” group according to whether the patients were selected by a certain pathological expression. We conducted a Bayesian network meta-analysis for all regimens in both groups; Results In unselected group, no regimen showed significant improvements in overall survival (OS) and progression free survival (PFS), while pembrolizumab and nivolumab combined with chemotherapy were ranked first and second respectively without an obvious safety difference. In selected group, zolbetuximab plus chemo-therapy significantly prolonged OS (HR 0.53, 95%CI 0.31–0.89) and PFS (HR 0.45, 95%CI 0.23–0.89). The top three regimens were zolbetuximab-chemotherapy, tratuzumab plus pertuzumab-chemotherapy and nivolumab-chemotherapy respectively, with no significant safety risk. Conclusion For average patients, immune checkpoint inhibitor PD-1 plus chemotherapy will be the promising regimen. For patients with overexpression of HER-2 or CLDN18.2, dual HER-2 targeting strategy or zolbetuximab combined with chemotherapy comes with greater survival benefits.