Meta-analysis Of The Efficacy And Safety Of VEGFR-TKIs In The Treatment Of Advanced Breast Cancer

ObjectiveTo systematically evaluate the efficacy and safety of vascular endothelial growth factor receptor-tyrosine kinase inhibitors(VEGFR-TKIs)in the treatment of advanced breast cancer,so as to provide evidence-based medical evidence for clinicians.MethodsFrom January 2010 to June 2022,Chinese Biomedical Literature Database,CNKI,VIP Database,Wanfang Database,Pub Med,Web of science,Embace,Clinicial.gov and other databases were searched by computer to evaluate the quality of randomized controlled trials that met the inclusion criteria,and analyzed by Rev Man5.4 and Stata17 software.ResultsA total of 21 randomized controlled trials involving 4295 patients were included.The results of meta-analysis showed that compared with non-VEGFR-TKIs group,VEGFR-TKIs group could improve the objective remission rate(RR=0.41,95 CI =0.22～0.61,P=0.004)and disease control rate(RR=0.44,95%CI=0.18～0.70,P=0.001)of patients with advanced breast cancer.In overall survival,the VEGFR-TKIs group(HR =1.26,95%CI=1.14～1.39,P=0.000)was shorter than the non-VEHGR-TKIs group,while the progression-free survival(HR=1.09,95%CI=0.99～1.19,P=0.077)was shorter than the non-VEGFR-TKIs group,but there was no significant difference between the two groups(P>0.05).There were significant differences in the objective remission rate and disease control rate between apatinib and anlotinib in the baseline subgroup analysis(P<0.05).The objective response rate(RR =0.95,95%CI=0.59～1.30)and disease control rate(RR=1.03,95%CI=0.66～1.39)of triple negative breast cancer in molecular typing were better than those of HER-2 negative breast cancer,and the differences were statistically significant(P<0.05).The objective response rate(RR=0.89,95%CI =0.56～1.21)and disease control rate(RR=0.85,95%CI=0.53～1.16)of the posterior line treatment in the line treatment type were significant,and the difference was statistically significant.In terms of safety,the incidence of grade ≥ 3gastrointestinal discomfort,myelosuppression,fatigue and fatigue in the VEGFR-TKIs group was significantly higher than that in the non-VEGFR-TKIs group,and the differences were statistically significant(P< 0.05).There was no significant difference in adverse reactions such as hypertension and hand-foot syndrome(P>0.05).Conclusion : Compared with the non-VEGFR-TKIs group,apatinib and anlotinib in the VEGFR-TKIs group can significantly improve the objective response rate and disease control rate of advanced triple-negative and HER-2-negative breast cancer in the post-line treatment,while sorafenib and sunitinib have no significant difference,but have no effect on the overall survival of patients;although gastrointestinal discomfort,bone marrow suppression,fatigue and other adverse reactions occurred in safety,they were within the tolerance range.Therefore,apatinib and anlotinib in VEGFR-TKIs may be of great significance in the backline treatment of advanced breast cancer.Conclusions(1)Compared with the control group,the VEGFR-TKIs group could improve the objective response rate and disease control rate of advanced breast cancer,but had no effect on the overall survival of patients.In the subgroup analysis,apatinib and anlotinib had significant effects in improving objective remission rate and disease control rate,while sorafenib and sunitinib had no significant difference.Patients with triple negative breast cancer and advanced posterior line treatment benefit more.(2)VEGFR-TKIs could not improve progression-free survival except sorafenib.(3)In the VEGFR-TKIs group,although gastrointestinal discomfort,bone marrow suppression,fatigue and fatigue adverse reactions occurred in the safety,they were all within the tolerance range.