, Volume 133, Issue 3, pp 1057-1065,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 15 Mar 2012

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

Previous publication Posters presented at ASCO, 29 May–2 June, 2009, Orlando, FL and the 32nd Annual San Antonio Breast Cancer Symposium, 9–13 December, 2009, San Antonio, TX.