Treatment-related toxicities of apatinib in solid tumors: a meta-analysis

BACKGROUND: Apatinib is a novel small molecular drug targeting vascular endothelial growth factor receptor-2 (VEGFR-2), which is being studied in multiple tumor types. We performed a meta-analysis to quantify the overall incidence and risk of hypertension, proteinuria, and hand-foot-syndrome (HFS) in cancer patients receiving apatinib. RESULTS: Altogether, 820 cancer patients from 7 prospective trials were included for the meta-analysis. The incidences of all-grade and high-grade hypertension were 45.4% and 9.7%. The incidences of all-grade and high-grade proteinuria were 45.1% and 3.7%. The incidences of all-grade and high-grade HFS were 35.9% and 8.6%. The RRs of all-grade hypertension, proteinuria and HFS of apatinib compared to placebo were increased (hypertension, RR = 6.53; proteinuria, RR = 2.62, and HFS, RR = 11.45). The RRs of developing high-grade hypertension and HFS were substantially higher than that of placebo (hypertension, RR = 7.73; HFS, RR = 7.23), but not for proteinuria (RR = 2.56, 95% CI: 0.57–11.52). MATERIALS AND METHODS: Prospective phase II and III clinical trials of cancer patients receiving apatinib were searched and included. Summary incidences, relative risk (RR), and 95% confidence intervals (CI) were calculated by using either fixed or random effects models according to the heterogeneity of the studies. CONCLUSIONS: Apatinib is generally well tolerated, and associated with increased risks of all-grade hypertension, proteinuria and HFS, and high-grade hypertension and HFS, but not high-grade proteinuria.