Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab.

Abstract

Abstract Background: BIBW 2992 (Tovok™*) is a novel, oral, irreversible inhibitor of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER)1 and 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 progressed following treatment with trastuzumab was conducted in the US and the UK.Methods: A multi-institutional, open-label, single-arm Phase II study was conducted. Eligible patients had stage IIIB or IV HER2-positive metastatic breast cancer, with progression following trastuzumab treatment or intolerance of trastuzumab, received no prior EGFR-targeted therapy, had measurable disease, Eastern Cooperative Oncology Group performance status of 0–2 and adequate organ function. Patients received 50 mg BIBW 2992 once-daily until disease progression. Tumor assessments were performed every two treatment courses (one course is 28 days). The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors). Safety data were also collected.Results: A total of 41 patients started treatment on the trial. Patients had received a median of three lines of prior therapy (range, 0–15). Thirty-four patients are evaluable for response. Of these, four patients had a partial response (PR) and eight patients had stable disease maintained for at least four cycles. One patient with confirmed PR remained on treatment until progression at 63 weeks. The most frequently observed side-effects to date are rash (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 in four patients [9.8%]) and diarrhea (CTCAE Grade 3) in nine patients. There have been 21 dose reductions in 18 patients.Conclusion: BIBW 2992 was safe and induced promising early clinical responses in HER2-positive breast cancer patients who have progressed following treatment with trastuzumab. Manageable cutaneous adverse events and diarrhea were the main side-effects.*Trade name not FDA approved. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5060.