Study Of TKI Antiangiogenic Drugs In The Treatment Of Advanced Breast Cancer

Objective:Summarize the efficacy and safety of TKI antiangiogenic drugs including apatinib and anlotinib in the treatment of refractory breast cancer.Explore the effects of different treatment regimens,doses and tumor characteristics on the efficacy,so as to provide reference for clinical practice.Method:A retrospective analysis was conducted.Collect the list of patients with advanced breast cancer who received apatinib or anlotinib treatment in our center from January 2017 to October 2021.Collect data of the patients,including age,gender,underlying diseases and other basic information.When the tumor recurrence,collect information of molecular classification,metastatic site,number of therapy lines,drug regimen,dose and other clinical data as well as the occurrence of adverse reactions.SPSS 26.0 software was used to analyze the objective response rate,clinical benefit rate,progression free survival time,overall survival time and the occurrence of adverse reactions.Result:1.A total of 58 eligible patients were screened according to the inclusion criteria and exclusion criteria.Most of the enrolled patients were treated in the back line,with severe conditions and accompanied by multiple drug resistance.2.Objective response rate（ORR）of refractory advanced breast cancer treated with TKI antiangiogenic drugs was 19.0%.Clinical benefit rate（CBR）was 77.6%.Median progression free survival（PFS）was 4.0 months（0.6～27.6 months）,and median overall survival（OS）was 10.5 months（1.0～40.3 months）.3.Subgroup analysis of efficacy indicated that:（1）There was no significant statistical difference in ORR、CBR、PFS、OS between more than or equal to third-line therapy patients and less than three-line therapy patients.（2）There was no significant statistical difference in ORR,CBR and PFS among different molecular types,and the OS of non-triple negative breast cancer was longer than that of triple negative breast cancer（P=0.008）.（3）ORR in patients treated with TKI combined with double-drug chemotherapy was higher than that in patients treated with TKI combined with single-drug chemotherapy（P=0.044）,but the PFS was shorter（P=0.042）in the former.There was no significant statistical difference in CBR and OS between the two groups.（4）In terms of dose,the higher the dose,the higher ORR and CBR（P=0.026）,but there was no significant statistical difference in PFS and OS among patients using different dose;（5）There was no significant statistical difference in ORR,CBR and PFS between patients with and without brain metastases.OS of patients with brain metastases was shorter than that in patients without brain metastases（P=0.014）.（6）The higher the ECOG score,the lower CBR,while there was no statistical significance in ORR and PFS of patients with different ECOG scores.4.Univariate and multivariate analyses suggested that liver metastasis and medication regimen were independent predictors of PFS.5.Analysis of adverse reactions suggested that in this study,the incidence rate of adverse reactions associated with TKI antiangiogenic drugs was 86.2%,and the common adverse reactions were fatigue,anorexia,skin and mucous ulcer and hand and foot syndrome,and the degree of most of adverse reactions was 1～2 degree.6.Subgroup analysis of adverse reactions suggested that even though there was no significant difference in the category and severity of adverse reactions between apatinib and anlotinib,but adequate tolerability of anlotinib was better.There was a positive correlation between drug dose and the incidence of adverse reactions.There was no significant statistical difference in the severity of adverse reactions between different drug doses（P>0.05）.Conclusion:1.For patients with advanced breast cancer,especially refractory ones with the failure of multi-line therapy,TKI antiangiogenic drug is a safe and effective treatment option.2.The application of TKI antiangiogenic drugs is not limited to triple negative breast cancer,non-triple negative breast cancer patients can also benefit from the therapy.In addition,the drug is effective in reducing brain metastasis sites and alleviating cerebral edema.3.TKI combined with single-drug chemotherapy is superior to combined with double-drug chemotherapy in terms of the choice of medication regimen.4.In terms of the selection of drug dose,it is recommended to give sufficient medication under the premise that patients can tolerate it.At the same time,close monitoring of adverse reactions and timely adjustment of drug dosage are necessary.5.ECOG score was not a factor limiting the application of TKI antivascular drugs.