Efficacy and safety of low-dose apatinib combined with chemotherapy as second-line treatment for advanced gastric cancer: a meta-analysis

Introduction: At present, there are several studies on low-dose apatinib combined with chemotherapy as a second-line treatment of advanced gastric cancer (AGC), but the conclusions are controversial. Therefore, this meta-analysis aims to evaluate the efficacy and safety of low-dose apatinib combined with chemotherapy as a second-line treatment of AGC. Methods: Nine databases were searched for records on apatinib combined with chemotherapy in treating AGC from inception to June 2022. The observation group received low-dose apatinib combined with chemotherapy, while the controls received chemotherapy alone or other non-placebo treatments. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The relative risk (RR) and weighted mean difference (WMD) were used as effect sizes. Results: Eight studies involving 679 patients were included in this meta-analysis. The results of the meta-analysis showed that the observation group was superior to the controls in terms of ORR (RR=1.38, 95% CI: 1.05 similar to 1.81, P = 0.02), DCR (RR= 1.35, 95%CI: 1.20 similar to 1.53, P<0.001], OS (WMD= 4.72, 95%CI: 0.71 similar to 8.72, P<0.001] and PFS (WMD= 2.67, 95%CI: 1.7 similar to 3.63, P<0.001). There were no significant differences between the two groups in adverse events of any grade except hypertension (RR = 2.82, 95%CI: 2.07 similar to 3.84, P < 0.001), hand-mouth syndrome (RR= 1.84, 95% CI: 1.84 similar to 2.48, P < 0.001), and proteinuria (RR = 3.63, 95%CI: 2.31 similar to 5.7, P < 0.001). Conclusion: low-dose apatinib combined with chemotherapy as a second-line therapy is more effective in improving the efficacy of AGC compared to chemotherapy alone. However, this option has the potential to increase the risk of hypertension, hand-mouth syndrome, and proteinuria.