Use of BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI), to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab.
Authors: Hickish, T., Wheatley, D., Lin, N., Carey, L., Houston, S., Mendelson, D., Solca, F., Uttenreuther-Fischer, M., Jones, H. and Winer, E.
Journal: J Clin Oncol
Volume: 27
Issue: 15_suppl
Pages: 1023
eISSN: 1527-7755
Abstract:1023 Background: BIBW 2992 (Tovok) is an oral, novel, and potent, irreversible dual epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) inhibitor, with preclinical activity in trastuzumab-resistant cell lines overexpressing HER2 and phase I clinical activity. A phase II study of BIBW 2992 in patients with HER2-positive breast cancer who have failed treatment with trastuzumab is currently being conducted in the US and the UK. METHODS: This is a multi-institutional open label single arm phase II study, planning to recruit 40 patients. Eligibility criteria include stage IIIB or IV HER2-positive metastatic breast cancer, progression following receipt of trastuzumab or intolerance of trastuzumab, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function. Patients receive 50 mg BIBW 2992 once daily until disease progression. Tumor assessments are performed every two courses (one course = 28 days). The primary endpoint is objective response rate (RECIST criteria). Safety data are also collected. RESULTS: To date, 40 patients have started treatment on the trial. Patients had received a median of three lines of prior therapy. Nine patients discontinued treatment prior to the first assessment at 8 weeks; four due to disease progression, four due to adverse events and one due to withdrawal of consent. Twenty-one patients have had tumor assessment after 8 weeks of treatment. Of these, four patients had a partial response (PR) and 10 patients had stable disease (SD). The PR has been confirmed at 16 weeks in one patient. The most frequently observed side effects to date are rash (Common Toxicity Criteria for Adverse Events [CTCAE] grade 3 in 4 patients) and diarrhea (CTCAE grade 3 in 8 patients). There were 20 dose reductions in 17 patients. CONCLUSIONS: BIBW 2992 at 50 mg/day induced responses and seems promising in HER2-positive breast cancer patients who have failed treatment with trastuzumab. Manageable cutaneous adverse events and diarrhea were the main side effects. [Table: see text].
Source: PubMed