A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab

作者：Lin Nancy U^*; Winer Eric P; Wheatley Duncan; Carey Lisa A; Houston Stephen; Mendelson David; Munster Pamela; Frakes Laurie; Kelly Steve; Garcia Agustin A; Cleator Susan; Uttenreuther Fischer Martina; Jones Hilary; Wind Sven; Vinisko Richard; Hickish Tamas

来源：Breast Cancer Research and Treatment, 2012, 133(3): 1057-1065.

DOI：10.1007/s10549-012-2003-y

• Breast cancer
• ErbB1
• ErbB2
• Human epidermal growth factor receptor
• Second-generation small molecule kinase inhibitors
• Trastuzumab

Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly blocks all kinase-competent ErbB family members. This phase II, open-label, single-arm study explored afatinib activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab treatment. Patients had stage IIIB/IV HER2-positive metastatic breast cancer, with progression following trastuzumab or trastuzumab intolerance and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received 50 mg afatinib once-daily until disease progression. Primary endpoint was objective response rate (Response Evaluation Criteria in Solid Tumors 1.0), with tumor assessments every 8 weeks. Forty-one patients were treated. Patients had received a median of three prior chemotherapy lines (range, 0-15) and 68.3% had received trastuzumab for > 1 year. Four patients (10% of 41 treated; 11% of evaluable patients) had partial response. Fifteen patients (37% of 41) had stable disease as best response and 19 (46% of 41) achieved clinical benefit. Median progression-free survival was 15.1 weeks (95% confidence interval [CI]: 8.1-16.7); median overall survival was 61.0 weeks (95% CI: 56.7-not evaluable). Most frequent common terminology criteria for adverse events grade 3 treatment-related adverse events were diarrhea (24.4%) and rash (9.8%). Afatinib monotherapy was associated with promising clinical activity in extensively pretreated HER2-positive breast cancer patients who had progressed following trastuzumab treatment.

• 出版日期2012-6