| Objective:Currently,there is no standard and unified treatment plan for recurrent glioblastoma in the world.In 2009,the FDA approved bevacizumab for patients with recurrent GBM.Compared with previous salvage regimens,the application of bevacizumab showed a relatively obvious survival benefit,but the overall survival is still short,and drug resistance is constantlu occurring.In recent years,new combination therapies have been proposed and clinical trials have been conducted to optimize the effect of bevacizumab.This paper intends to use the method of network meta analysis to comprehensively evaluate the efficacy and safety of these therapies,so as to provide certain references for clinical work.Methods:Searching the major databases,we choosd random clinical trials that evaluated bevacizumab combined treatment for recurrent glioblastoma.Using cochrane bias risk assessment tool to evaluate the original researches,using Stata 15.0(random effect model)to analysis.To evaluate the consistency of the closed loop,we used the inconsistency factor.Furthermore,Funnel plots were used to evaluate whether there was a small sample effect.The cumulative probability ranking graph was drawn to estimate the ranking of the curative effect by SUCRA.Results:Four outcome indicators are adopted in this study to evaluate therapies,includi ng 6-PFS%、m-PFS、m-OS、≥level 3 adverse events incidence.From the results o f pairwise comparisons,bevacizumab+lomustine(90 mg/m~2),compared with lomusti ne monotherapy scheme,has obvious advantage in improving 6-PFS%(OR=2.76,95%CI[1.22,6.27]).For the improvement of m-PFS,bevacizumab plus low dose lom ustine therapy is worse than bevacizumab single regimen、bevacizumab+VB-111 and lomustine monotherapy,HR=1.88,95%CI[1.06,3.32]、HR=2.44,95%CI[1.12,5.35]、HR=2.42,95%CI[1.60,3.65].In terms of overall survival,bevacizumab+VB-111 was s uperior to low-dose bevacizumab+low-dose lomustine and bevacizumab+low-dose lo musine,HR=0.48 95%CI[0.24,0.95]、HR=0.62 95%CI[0.39,0.99].In terms of safety,c ompared with bevacizumab+temozolomide,the incidence of≥grade 3 adverse event s was higher in bevacizumab+CPT group,OR=2.34 95%CI[1.07,5.14].Compared with bevacizumab monotherapy,bevacizumab+CPT、bevacizumab+VB-111 was more likel y to have adverse events,OR=2.04 95%CI[1.10,3.80],OR=3.77 95%CI[2.25,6.34].On the contrary,bevacizumab+carboplatin is better than bevacizumab+VB-111,OR=0.3495%CI[0.14,0.83].From the perspective of the ranking of each treatment plan:in te rms of increasing 6-PFS%,the top three are:bevacizumab+lomustine,bevacizumab+low-dose lomustine,bevacizumab+etoposide;in terms of prolonging m-PFS,bevaci zumab+etoposide,bevacizumab+low-dose lomustine,and bevacizumab+vorinostat have advantages;in the incidence of adverse events of grade≥3,patients were relatively well tolerated with bevacizumab+vorinostat,bevacizumab,and bevacizumab+carboplat in.Conclusion:The treatment strategy of bevacizumab+lomustine has an advantage in prolonging the progression-free survival rate of 6 months;in prolonging the progression-free survival time,bevacizumab+etoposide is better;low-dose bevacizumab+low-dose lomustine can obtain a longer overall survival time in comparison;patients are more tolerant to the bevacizumab+vorinostat treatment regimen. |
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