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

Wei Zhao,Zefei Jiang,Tao Wang,Shaohua Zhang,Jianbin Li,Li Bian,Fengrui Xu

doi:10.21147/j.issn.1000-9604.2020.03.07

Abstract

ObjectiveSeveral 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.MethodsA 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.ResultsAfter 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). ConclusionsThe 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.

Highlights

Trastuzumab was confirmed to provide significantly improved clinical benefits and formed the foundation of modern biotarget therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer [1,2,3,4]
Switching to the lapatinib-contained regimen is an option for patients with HER2-positive disease following progression on a trastuzumab-containing regimen according to National Comprehensive Clinical Network (NCCN) panel
Patients were classified into three different groups by subsequent treatment: 78 (22.8%) received chemotherapy only, 148 (43.3%) continued to receive trastuzumab plus chemotherapy, and 116 (33.9%) received lapatinib plus chemotherapy

Summary

Introduction

Trastuzumab was confirmed to provide significantly improved clinical benefits and formed the foundation of modern biotarget therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer [1,2,3,4]. The National Comprehensive Clinical Network (NCCN) guidelines [9] recommends trastuzumab emtansine (TDM1) as a preferred option for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have previously received a trastuzumab-based regimen [10]. The clinical activity of lapatinib-containing regimens has been demonstrated in women with HER2-positive breast cancer that progressed despite trastuzumab treatment [13,14,15]. Several trials have demonstrated benefit of continuing trastuzumab therapy following disease progression on a trastuzumab-containing regimen [16,17,18]. The NCCN panel [9] recommends the continuation of a trastuzumab regimen and switching to other chemotherapy drugs for patients with HER2-positive disease following progression on a trastuzumab-containing regimen

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Discussion

Conclusion