Effectiveness of second-line anti-HER2 treatment in HER2-positive metastatic breast cancer patients previously treated with trastuzumab: A real-world study

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.