LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment

Inclusion criteria:

• Histologically confirmed diagnosis of HER2-overexpression breast cancer
• Stage IV metastatic disease
• Must have progressed on one prior trastuzumab treatment
• no more than one prior trastuzumab based therapy regimen (either adjuvant or first-line)
• Must have received anthracycline and/or taxane based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer
• Must have (archived) tumour tissue sample available for central re-assessment of HER2-status
• At least one measurable lesion according to RECIST 1.1.
• ECOG score of 0 or 1 .

Exclusion criteria:

• Prior treatment with EGFR/HER2-targeted small molecules or antibodies other than trastuzumab
• Prior treatment with vinorelbine
• Known pre-existing interstitial lung disease
• Active brain metastases
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomisation.
• Cardiac left ventricular function with resting ejection fraction of less than 50%.
• Patients unable to comply with the protocol.
• Any contraindications for therapy with vinorelbine or trastuzumab.
• Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
• Use of any investigational drug within 4 weeks of randomisation.
• Inadequate hepatic, renal and haematologic organ function