Efficacy And Safety Of Apatinib Versus Tegafur In The Treatment Of Advanced Gastric Cancer: A Meta-analysis

Objective: Gastric cancer is one of the most common malignancies in the world,ranking second only to lung cancer in cancer-related deaths.In the second-line treatment of advanced gastric cancer,the NCCN guidelines put forward six chemotherapy regimens.However,there are still some adverse events such as second-line treatment failure,poor treatment effect,serious adverse reactions and poor tolerance of patients,which remains to be solved.Apatinib,being as a new targeted drug for the treatment of advanced gastric cancer,has attracted people's attention.However,those studies which discuss the treatment of efficacy and safety between apatinib and tegafur after first-line treatment failure in advanced gastric cancer are less,thus,our aim of this meta-analysis was to further explore the efficacy and safety between apatinib and tegafur,to provide a reference for clinical treatment and to make guideline by conducted a meta-analysis of those published RCT studies.Methods: The study from Pub Med,Embase,the Cochrane library,China National Knowledge Infrastructure(CNKI)and Wanfang Medical Network was retrieved those published literature from the establishment of database to December 2019.We explored all those literature to get a full understanding of the subject,define the inclusion and exclusion criteria,and extract the research of pre-inclusion analysis.We used the Jadad scale to evaluate the quality of each literature,and we collected all those effective data from them.All statistical analyses and systematic reviews were performed with STATA version 16.0 software packages(STATA,College Station,TX).Heterogeneity among published studies was assessed,and we used the sensitivity analysis and Egger's test in publication bias to investigate the stability and reliability of analysis results.Results: A total of 15 randomized controlled trials(RCT)involving 1071 patients were included in this study.Patients in the apatinib group had higher objective remission rate(ORR)and disease control rate(DCR)than those in the tegafur group(objective remission rate: OR=1.84,95%CI=1.42-2.39,P<0.001;Disease control rate: OR=2.02,95%CI=1.48-2.76,P<0.001).In the subgroup analysis,patients with single-drug/two-drug combination in the first-line chemotherapy were higher in ORR than those in the tegafur group(OR=2.03,95%CI=1.14-3.63,P=0.016).In second-line treatment,patients in the apatinib group were superior in both ORR and DCR to those in the tegafur group(ORR: OR=1.80,95%CI=1.31-2.47,P < 0.001).DCR: OR=1.78,95%CI =1.20-2.63,P=0.004),and both ORR and DCR were better in apatinib group no matter how initial dose were than those in the tegafur group(ORR: 850 mg group: OR=1.92,95%CI=1.30-2.83,P=0.001;?500mg : OR=1.76,95%CI=1.12-2.77,P=0.013.DCR: 850 mg group:OR=1.93,95%CI=1.22-3.04,P=0.005;?500mg : OR=2.42,95%CI=1.48-3.95,P < 0.001).In terms of quality of life,there was no statistical significance in the apatinib group compared with the tegafur group(OR=0.11,95%CI=-0.00-0.22,P=0.06).In terms of adverse reactions,the incidence of hypertension and proteinuria in the apatinib group was higher than that in the tegafur group(hypertension: OR=3.73,95%CI=1.75-7.95,P<0.001;Proteinuria: OR=16.05,95%CI=4.97-51.82,P<0.001);In terms of nausea and vomiting,diarrhea,fatigue,neutropenia and stomatitis,the incidence of adverse reactions in apatinib group was lower than that in tegafur group(nausea and vomiting: OR=0.54,95%CI=0.30-0.97,P=0.040;Diarrhea: OR=0.37,95%CI=0.25-0.55,P<0.001;Neutropenia: OR=0.18,95%CI=0.06-0.59,P=0.004;Stomatitis: OR=0.35,95%CI=0.19-0.63,P<0.001).The differences in the above studies were statistically significant.There was no significant difference between apatinib group and tegafur group in the incidence of fatigue and hand-foot syndrome(Fatigue:OR=0.31,95%CI=0.10-1.00,P=0.049;Hand-foot syndrome:OR=1.41,95%CI=0.63-3.17,P=0.070).Conclusion:1.In those patients with advanced gastric cancer who failed in the first-line treatment,apatinib have a significant advantage in both ORR and DCR compared with tegafur,especially in patients who experienced single-drug/two-drugs in the first-line chemotherapy.Moreover,apatinib was improved to be more effective and safety in the second-line therapy,and the advantage does not change whatever the initial dose is.2.In terms of adverse reactions,apatinib increased the incidence of hypertension and proteinuria,but it could be controlled by dose reduction or drug withdrawal,while the adverse reactions in tegafur group were more significant than the apatinib group in terms of nausea,vomiting,diarrhea,neutropenia and stomatitis.On the whole,compared with tegafur,apatinib has better efficacy and safety for patients with advanced gastric cancer after the failure of first-line treatment.