The efficacy of human epidermal growth factor receptor 2 (HER2) blockade switching mode in refractory patients with HER2-positive metastatic breast cancer: a phase II, multicenter, single-arm study (SYSUCC-005)

Fangfang Duan, Muyi Zhong, Yuyu Ma, Chenge Song, Lehong Zhang, Ying Lin, Zhiyong Wu, Yuanqi Zhang, Jiajia Huang, Fei Xu, Yanxia Shi, Shusen Wang, Zhongyu Yuan, Wen Xia, Xiwen Bi, Fangfang Duan, Muyi Zhong, Yuyu Ma, Chenge Song, Lehong Zhang, Ying Lin, Zhiyong Wu, Yuanqi Zhang, Jiajia Huang, Fei Xu, Yanxia Shi, Shusen Wang, Zhongyu Yuan, Wen Xia, Xiwen Bi

Abstract

Background: Despite significant survival improvement in human epidermal growth factor receptor 2 (HER2) blockade for HER2-positive breast cancer, resistance to anti-HER2 remains inevitable. Subsequent anti-HER2 with continuing trastuzumab beyond progression is acceptable with limited efficacy when other anti-HER2 treatment is unavailable. This single-arm, phase II study (SYSUCC-005) aimed to explore the efficacy of switching mode for HER2-positive refractory metastatic breast cancer.

Methods: Patients with HER2-positive metastatic breast cancer rapidly progressing during pre-trastuzumab from six hospitals in China were designed to switch to lapatinib 1,250 mg orally once per day continuously plus capecitabine (1,000 mg/m2 orally twice per day on days 1-14) or vinorelbine (25 mg/m2 intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS).

Results: Between January 5, 2015 and May 31, 2020, 159 patients were eligible in this study. The median follow-up was 33.1 months, a median PFS of 8.5 months was achieved. Brain metastases (hazard ratio [HR] = 1.582, 95% confidence interval [CI] 1.019- 2.453, P = 0.041) and ≥ 2 metastatic sites (HR = 1.679, 95% CI 1.151-2.450, P = 0.007) were independent prognostic factors for PFS. The most common grade ≥ 3 adverse events were diarrhea (3.8%) and hand-foot syndrome (9.4%).

Conclusion: The switching mode showed predominant efficacy, which might be a prior therapeutic option over continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer.

Trial registration: This trial was registered on ClinicalTrials.gov ( NCT02362958 ) on 13/02/2015.

Keywords: HER2 blockade therapy; HER2-positive breast cancer; Lapatinib; Trastuzumab refractory.

Conflict of interest statement

The authors declare that they have no competing interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart of patients through this SYSUCC-005 trial
Fig. 2
Fig. 2
Kaplan–Meier curves for all patients enrolled in this trial. A: The Kaplan–Meier curve for progression-free survival (PFS). B: The Kaplan–Meier curve for overall survival (OS)

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