Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression

Inclusion Criteria

• Histologically documented, locally advanced, or metastatic breast cancer; measurable and/or non-measureable but evaluable disease is permitted
• HER2-positive disease
• History of prior trastuzumab therapy
• Life expectancy ≥ 90 days as assessed by the investigator
• Negative urine pregnancy test ≤ 72 hours prior to Cycle 1 Day 1 for all women of childbearing potential
• For patients of childbearing potential, agreement to use one highly effective form of contraception or two effective forms of contraception for the duration of the study treatment(s) and for 4 months after the last dose of T-DM1 or 6 months after the last dose of pertuzumab, if applicable

Exclusion Criteria

• Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 2 weeks of the first study treatment
• Prior T-DM1 or pertuzumab therapy
• History of intolerance (such as Grade 3-4 infusion reaction) and/or adverse events related to trastuzumab
• Grade ≥ 2 (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v3) peripheral neuropathy at the time of or within 3 weeks prior to the first study treatment
• Brain metastases that are untreated or progressive or have required any type of therapy, including radiation, surgery, and/or steroids, to control symptoms from brain metastases within 60 days prior to the first study treatment
• History of cardiac disease, unstable angina, symptomatic congestive heart failure (CHF) (Class ≥ II per the New York Heart Associate [NYHA] guidelines), myocardial infarction, or ventricular arrhythmia ≤ 6 months prior to Cycle 1, Day 1
• Implantable pacemaker or automatic implantable cardioverter defibrillator
• Congenital long QT syndrome or family history of long QT syndrome
• Current uncontrolled hypertension
• Current treatment with medications that alter cardiac conduction (e.g., digitalis, beta-blockers, or calcium channel blockers) or medications that are generally accepted to have a risk of causing torsades de pointes (TdP)
• Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• Major surgical procedure or significant traumatic injury within 28 days prior to first study treatment, or anticipation of the need for major surgery during the course of study treatment