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)

• Published in: BMC cancer 2022-03, Vol.22 (1), p.271-271, Article 271
• Main Authors: Duan, Fangfang, Zhong, Muyi, Ma, Yuyu, Song, Chenge, Zhang, Lehong, Lin, Ying, Wu, Zhiyong, Zhang, Yuanqi, Huang, Jiajia, Xu, Fei, Shi, Yanxia, Wang, Shusen, Yuan, Zhongyu, Xia, Wen, Bi, Xiwen
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer; Development and progression; Drug therapy; Epidermal growth factor; Female; Health aspects; HER2 blockade therapy; HER2-positive breast cancer; Humans; Lapatinib; Metastasis; Oncology, Experimental; Patient outcomes; Receptor, ErbB-2 - metabolism; Risk factors; Trastuzumab - therapeutic use; Trastuzumab refractory; Treatment Outcome
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09399-2

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. 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/m orally twice per day on days 1-14) or vinorelbine (25 mg/m intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS). 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%). 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. This trial was registered on ClinicalTrials.gov ( NCT02362958 ) on 13/02/2015.