摘要
Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.
基金
Capital Clinical Medicine Special Project(No.Z181100001718215)
National Natural Science Foundation of China(No.81602314).Research number:CSCO-BC RWS 16002。
