Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer

The study was terminated based on the IDMC recommendation in 2012, collection of efficacy
outcome measures was discontinued and all primary and secondary outcome measures were
reported in 2012.

An amendment protocol allowed subjects who were on study treatment to enroll in a Long Term
Follow Up (LTFU) phase if they had evidence of clinical benefit but no local access to
standard of care treatments. Subjects received study treatment until disease progression,
unacceptable toxicity, or subject withdrawal. In LTFU only Adverse Events data were
collected. For the LTFU the Outcome Measure "Number of participants with the indicated Grade
3 or Grade 4 Adverse Events (AEs) occurring in >=2% of participants in either treatment arm"
and "Adverse Events" were updated.

Inclusion Criteria:

- Females at least 18 years old;

- ECOG Performance Status 0-2;

- Histologically or cytologically confirmed HER2-positive invasive breast cancer, with
Stage IV disease;

- Prior treatment with taxanes or anthracyclines is required;

- Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and
radiation therapy is permitted;

- Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal;

- Concurrent treatment with bisphosphonates is permitted, however treatment must be
initiated prior to the first dose of study therapy;

- Able to swallow and retain oral medications;

- Women with potential to have children must be willing to practice acceptable methods
of birth control during the study;

- Normal organ and marrow function.

Exclusion Criteria:

- History and/or current evidence of CNS metastases. Baseline MRI scan by Independent
Reviewer to confirm no brain mets;

- Concurrent treatment with an investigational agent or participation in another
treatment clinical trial;

- Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including
but not limited to trastuzumab-DM1 and neratinib) and capecitabine;

- Known DPD deficiency;

- Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or
hormonal therapy for treatment of cancer;

- History of allergic reactions attributed to compounds chemically related to lapatinib
(quinazolines), capecitabine, fluorouracil or any excipients;

- Concomitant use of CYP3A4 inhibitors or inducers;

- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel;

- History of immediate or delayed hypersensitivity reaction to gadolinium contrast
agents, or other contraindication to gadolinium contrast and other known
contraindication to MRI;

- Concurrent disease or condition that would make the subject inappropriate for study
participation or any serious medical or psychiatric disorder that would interfere with
the patient's safety or compliance to study procedures;

- have acute or currently active/requiring anti-viral therapy hepatic or biliary disease
(with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver
metastases or stable chronic liver disease);

- Any on-going toxicity from prior anti cancer therapy except alopecia;

- Active cardiac disease;

- Uncontrolled infection;

- History of other malignancy, unless curatively treated with no evidence of disease for
at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated
non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are
eligible;

- Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
preceding the first dose of protocol treatment;

- Pregnant or lactating females.