LUX-Breast 1; An Open Label, Randomised Phase III Trial of BIBW 2992 and Vinorelbine Versus Trastuzumab and Vinorelbine in Patients With Metastatic HER2-overexpressing Breast Cancer Failing One Prior Trastuzumab Treatment

Inclusion Criteria

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