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

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

doi:10.21147/j.issn.1000-9604.2020.03.07

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

Chin J Cancer Res. 2020 Jun;32(3):361-369. doi: 10.21147/j.issn.1000-9604.2020.03.07.

Authors

Wei Zhao^{1

2

3}, Li Bian², Tao Wang², Shaohua Zhang², Jianbin Li^{1

2}, Fengrui Xu^{1

2}, Zefei Jiang²

Affiliations

¹ Department of Breast Oncology, Academy of Military Medical Sciences, Beijing 100850, China.
² Department of Breast Oncology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
³ PLA Rocket Force Characteristic Medical Center, Beijing 100088, China.

PMID: 32694900
PMCID: PMC7369172
DOI: 10.21147/j.issn.1000-9604.2020.03.07

Abstract

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.

Keywords: Metastatic breast cancer; real-world study; second-line; trastuzumab failure.