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.
* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 .

Exclusion criteria:

* Prior treatment with Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor(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