A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Carboplatin; Docetaxel; Pertuzumab; Trastuzumab; Trastuzumab Emtansine
Intervention description: Carboplatin IV infusion at a dose to achieve an AUC of 6 mg*min/mL q3w; Docetaxel 75 mg/m^2 IV infusion q3w; Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w; Trastuzumab 8 mg/kg (loading dose); and 6 mg/kg (maintenance dose) IV infusion q3w; Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w
Intervention MeSH terms: Carboplatin; Docetaxel; Trastuzumab; Pertuzumab; Maytansine; Ado-Trastuzumab Emtansine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 444.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants
      with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early
      breast cancer (EBC) whose primary tumors were greater than or equal to (>/=) 2 centimeters
      (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine +
      pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab
      (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by
      surgery, and an adjuvant treatment period.

      Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of
      consent, or study termination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed invasive breast cancer with a primary tumor size of greater
             than (>) 2 cm

          -  HER2-positive breast cancer

          -  Participants with multifocal tumors (more than one tumor confined to the same quadrant
             as the primary tumor) are eligible provided all discrete lesions are sampled and
             centrally confirmed as HER2 positive

          -  Stage at presentation: cT2-cT4, cN0-cN3, cM0, according to American Joint Committee on
             Cancer (AJCC) staging system

          -  Known hormone receptor status of the primary tumor

          -  Participant agreement to undergo mastectomy or breast-conserving surgery after
             neoadjuvant therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Baseline Left Ventricular Ejection Fraction (LVEF) >/= 55 percent (%) measured by
             echocardiogram (ECHO) or multiple-gated acquisition (MUGA)

          -  Effective contraception as defined by protocol

        Exclusion Criteria:

          -  Stage IV (metastatic) breast cancer

          -  Participants who have received prior anti-cancer therapy for breast cancer except
             those participants with a history of breast lobular carcinoma in situ (LCIS) that was
             surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with
             mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from
             surgery until diagnosis of current breast cancer

          -  Participants with multicentric (multiple tumors involving more than 1 quadrant) or
             bilateral breast cancer

          -  Participants who have undergone incisional and/or excisional biopsy of primary tumor
             and/or axillary lymph nodes

          -  Axillary lymph node dissection or positive sentinel lymph node prior to start of
             neoadjuvant therapy

          -  History of concurrent or previously non-breast malignancies except for appropriately
             treated (1) non-melanoma skin cancer and (2) in situ carcinomas, including cervix,
             colon, and skin. A participant with previous invasive non-breast cancer is eligible
             provided he/she has been disease-free >/= 5 years

          -  Treatment with any investigational drug within 28 days prior to randomization

          -  Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
             CTCAE) version (v) 4.0

          -  Any significant concurrent medical or surgical conditions or findings that would
             jeopardize the participant's safety or ability to complete the study

          -  Current pregnancy or breastfeeding