Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

Inclusion Criteria:

- Signed the informed consent form (ICF)

- Female, ≥18 years of age

- Histologically verified breast cancer with distant metastases (metastatic breast
cancer)

- Documentation of HER2 overexpression or gene amplification in the invasive component
of either the primary tumor or metastatic disease site defined as:

- 3+ by IHC and/or

- HER2/neu gene amplification by fluorescence, chromogenic or silver in situ
hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH
or SISH HER2 gene copies to chromosome 17 signal ratio of ≥2.0]

- Completed 12 to 24 weeks of first- or second-line treatment with trastuzumab in
combination with chemotherapy

- Either complete disappearance of all lesions, or persistence of metastatic disease
(stable disease) without unequivocal progression or the occurrence of new lesions

- Documentation of lesion response during the course of therapy received prior to
randomization (i.e., improvement or no worsening of tumor burden; the absence of new
lesions)

- Measurable disease is not required for study participation

- No known or suspected (associated neurological signs and symptoms) brain metastases
(including leptomeningeal involvement)

- Stable brain metastasis (defined as asymptomatic and off steroids ≥3 months) are
permitted in subjects entering LPT112515 on second-line treatment (completed 12-24
weeks of second-line treatment with trastuzumab plus chemotherapy)

- Baseline of Left Ventricular Ejection Fraction (LVEF) ≥50% measured by
echocardiography (ECHO) or multi-gated acquisition scan (MUGA)

- Completion of screening assessments (Refer to protocol for further details)

- Have adequate marrow and organ function as defined in Table 2. Table 2 Laboratory
Values SYSTEM LABORATORY VALUES Hematologic ANC ≥1.5 x 109/L Hemoglobin ≥9 g/dL (after
transfusion if needed) Platelets ≥100 x 109/L Hepatic Albumin ≥2.5 g/dL Serum
bilirubin ≤1.5 x ULN unless due to Gilbert's syndrome AST and ALT ≤3 x ULN Renal
Calculated creatinine clearance* ≥ 40 mL/min Serum Creatinine ≤1.5 mg/dL or
132.6μmol/L *Calculated by the Cockcroft-Gault Equation (Refer to protocol for
details) Abbreviations: ANC, absolute neutrophil count; ULN, upper limit of normal;
AST, aspartate aminotransferase; ALT, alanine aminotransferase

Exclusion Criteria:

- History of other malignancy. Subjects who have been disease-free for 5 years or
subjects with a history of completely resected non-melanoma skin cancer (basal or
squamous) are eligible

- Eastern Cooperative Oncology Group (ECOG) Performance Status >2

- Concurrent anti-cancer treatment, except anti-hormonal therapy for subjects with
hormone receptor positive breast cancer

- Concurrent treatment with an investigational agent

- Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib

- Concurrent treatment with protocol-defined prohibited medications (refer to protocol
for details)

- Serious cardiac illness or medical condition including but not confined to:

- Uncontrolled arrhythmias

- Uncontrolled or symptomatic angina

- History of congestive heart failure (CHF)

- Myocardial infarction <6 months from study entry

- Acute or current active (requiring anti-viral therapy) hepatic or biliary disease
(with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones,
liver metastases or stable chronic liver disease per investigator assessment)

- Concurrent disease or condition that may interfere with study participation, or any
serious medical disorder that would interfere with the subject's safety (for example,
active or uncontrolled infection or any psychiatric condition prohibiting
understanding or rendering of informed consent)

- Women of childbearing potential, including women whose last menstrual period was <12
months ago (unless surgically sterile) who are unable or unwilling to use adequate
contraceptive measures during the study treatment period. Adequate contraception
includes intra-uterine device, barrier methods with spermicide, or oral contraceptives
(unless clinically contraindicated for the subject population or per local practice,
refer to protocol for further details)

- Pregnant or lactating females

- Any clinically significant gastrointestinal abnormalities that may alter absorption
such as malabsorption syndrome or major resection of the stomach or bowels.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the study agents or their excipients that, in the opinion
of the Investigator or GSK medical monitor , contra-indicates participation