Although paclitaxel plus ramucirumab has been recommended as the preferred second-line strategy, other regimens also display potentially comparable efficacies. Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO meeting libraries. Randomized controlled trials featuring comparisons between different systemic treatments among previously treated patients with advanced gastric cancer were eligible for our systematic review. Network calculation were based on random-effects model and the relative ranking of each regimen was numerically indicated by P-score (CRD42018104672). Concerning second-line regimens, "paclitaxel plus olaparib" and "paclitaxel plus ramucirumab" dominated the overall survival ranking while "paclitaxel plus ramucirumab" additionally topped the hierarchy for progression-free survival. Among refractory or third-line only cases, apatinib reigned the hierarchy by significantly and insignificantly surpassing placebo and nivolumab respectively. In conclusion, paclitaxel plus ramucirumab is the optimal second-line regimen. Both apatinib and nivolumab could be potentially recommended as refractory regimens.

BACKGROUND AND PURPOSE:Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that targets VEGFR-2. Recent clinical trials have revealed its broad-spectrum anticancer effect. However, most recent studies of apatinib have involved single-arm studies with insufficient cases, different doses of drugs, and different incidences of adverse events (AEs), which has resulted in a lack of accurate measurement of the efficacy and safety of apatinib. Thus, we performed this meta-analysis to evaluate the efficacy and safety of apatinib. METHODS:In total, 21 studies from five databases (PubMed, ScienceDirect, ClinicalTrials.gov, China National Knowledge Infrastructure [CNKI], and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed using Stata 14.0 software. We used objective response rate (ORR) and disease control rate (DCR) to evaluate the efficacy of apatinib for five major types of solid tumors. Additionally, we used the total incidence of AEs and the incidence of the three most common grade 3-4 AEs to evaluate the safety of apatinib. RESULTS:The pooled results for the efficacy of apatinib in the treatment of different types of solid tumors revealed that patients treated with apatinib exhibited good disease control. In addition, it was likely that an increased dose of apatinib resulted in an increased ORR in lung and breast cancer and an increased DCR in liver and gastric cancer. Although AEs appeared in 84% of patients included in this meta-analysis, most of these AEs were of grades 1-2 and were well tolerated and controlled. The most common grade 3-4 AEs included hypertension, hand-foot syndrome, and proteinuria. Importantly, there were no significant differences in these grade 3-4 AEs with higher doses of apatinib. CONCLUSION:Apatinib is a novel VEGFR-2 inhibitor with proven efficacy and safety for solid tumors. The meta-analysis reveals the broad-spectrum anticancer effect of apatinib.

AIM:This meta-analysis was performed to evaluate the efficacy and safety of apatinib in patients with advanced gastric cancer (AGC). METHODS:After evaluating the inclusion and exclusion criteria, the data of eligible randomized clinical trials (RCTs) were extracted. Outcomes including objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed in the meta-analysis. RESULTS:Data of 1,069 patients from 13 RCTs were statistically analyzed. Pooled odds ratio (OR) for ORR and DCR was found to be 0.46 (95% confidence interval [CI]: 0.33, 0.64; <0.00001) and 0.23 (95% CI: 0.15, 0.36; <0.00001), respectively. Compared with placebo, apatinib showed statistical significance in AEs at any grade, including leucopenia, neutropenia, thrombocytopenia, diarrhea, hypertension, proteinuria, hand-foot syndrome, and fatigue (all <0.05). CONCLUSION:The results of our meta-analysis revealed that apatinib shows short-term efficacy over no-apatinib regimens or placebo regardless of its use as first- or second-line chemotherapy or for further treatment in patients with AGC accompanied with apparent AEs of any grade.