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).

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.

• Authors: 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
• Journal: BMC cancer (BMC Cancer) Vol. 22 Issue 1 Pg. 271 (Mar 15 2022) ISSN: 1471-2407 [Electronic] England
• PMID: 35291977 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2022. The Author(s).

Chemical References

• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Antineoplastic Combined Chemotherapy Protocols
• Breast Neoplasms (drug therapy, pathology)
• Female
• Humans
• Receptor, ErbB-2 (metabolism)
• Trastuzumab (therapeutic use)
• Treatment Outcome