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 aimed 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% confidence interval [CI]: 1.05–1.81, p = 0.02), DCR (RR = 1.35, 95% CI: 1.20–1.53, p < 0.001), OS (WMD = 4.72, 95% CI: 0.71–8.72, p < 0.001), and PFS (WMD = 2.67, 95% CI: 1.7–3.63, 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: 2.07–3.84, p < 0.001), hand-mouth syndrome (RR = 1.84, 95% CI: 1.84–2.48, p < 0.001), and proteinuria (RR = 3.63, 95% CI: 2.31–5.7, 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.