A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab emtansine; Treatment of physician's choice
Intervention description: The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change > 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.; The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for late-line HER2-positive metastatic breast cancer treatment after receipt of both trastuzumab- and lapatinib-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone [LHRH] agonist) hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Participants who had documented progressive disease (PD) were eligible to switch treatment to receive trastuzumab emtansine 3.6 mg/kg. Participants who switched treatment remained on trastuzumab emtansine treatment until another PD event or unmanageable toxicity.
The formulation, storage, and preparation of all TPC were as per the appropriate package insert or national prescribing information.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 602.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, multicenter, 2-arm, open-label study (TH3RESA) will evaluate the efficacy
      and safety of trastuzumab emtansine (T-DM1) in comparison with treatment of the physician's
      choice in participants with metastatic or unresectable locally advanced/recurrent human
      epidermal growth factor receptor 2 (HER2)-positive breast cancer. Eligible participants will
      be randomized to receive either trastuzumab emtansine 3.6 mg/kg intravenously every 21 days
      or treatment of the physician's choice. Participants continue to receive study treatment
      until disease progression or unacceptable toxicity occurs. This study is also known under
      Roche study protocol number BO25734.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants ≥ 18 years of age.

          -  Histologically or cytologically documented breast cancer.

          -  Metastatic or unresectable locally advanced/recurrent breast cancer.

          -  HER2-positive disease by prospective laboratory confirmation.

          -  Disease progression on the last regimen received as defined by the investigator.

          -  Prior treatment with an trastuzumab, a taxane, and lapatinib.

          -  Disease progression after at least two regimens of HER2-directed therapy in the
             metastatic or unresectable locally advanced/recurrent setting.

          -  Adequate organ function, as evidenced by laboratory results.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

          -  Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multi gated
             acquisition scan.

        Exclusion Criteria:

          -  Chemotherapy ≤ 21 days before first study treatment.

          -  Trastuzumab ≤ 21 days before first study treatment.

          -  Lapatinib ≤ 14 days before first study treatment.

          -  Prior enrollment in a trastuzumab emtansine containing study, regardless whether the
             patient received prior trastuzumab emtansine.

          -  Brain metastases that are untreated or symptomatic, or require any radiation, surgery
             or corticosteroid therapy to control symptoms within 1 month of randomization.