a study to evaluate the efficacy and safety of trastuzumab emtansine versus the combination of trastuzumab plus docetaxel in patients with her2-positive breast cancer

Conditions: Metastatic Breast Cancer

Summary: this is a phase iii, randomized, multicenter, multinational, two-arm, open-label clinical trial to investigate a first-line treatment of participants with human epidermal growth factor receptor-2 (her2)-positive metastatic breast cancer. the study will enroll patients with her2-positive, unresectable, locally advanced breast cancer (bc) if they have recurrent disease or progressive disease (pd) despite primary multi-modality therapy, and/or metastatic bc if they have not received prior chemotherapy for their metastatic disease. eligible participants at up to approximately 40 sites in the asia-pacific region will be randomized in a 2:1 ratio to receive trastuzumab emtansine (arm a) or trastuzumab plus docetaxel (arm b). all study drugs will be administered at in-clinic visits occurring every three weeks during the treatment phase. trastuzumab plus docetaxel was chosen as the comparator in the control group (arm b), as it represents a common first-line treatment option used in this patient population in china and other asia-pacific countries.


Eligibility criteria:
inclusion criteria: * age \>/= 18 years * her2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or in situ hybridization positivity, prospectively confirmed by a sponsor-designated central laboratory prior to enrollment * histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease appropriate for chemotherapy * patients must have measurable and/or non-measurable disease that is evaluable per the response evaluation criteria in solid tumors (recist) criteria, version 1.1 * eastern cooperative oncology group (ecog) performance status of 0 or 1 * adequate organ function * for women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use two adequate non-hormonal forms of contraception during treatment and for at least 6 months after the last dose of study drug exclusion criteria: * pregnancy or lactation * current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures, except bone fractures because of disease under study) * currently known active infection with hiv, hepatitis b virus (hbv), or hepatitis c virus (hcv) * major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment * current peripheral neuropathy grade \>/= 2 per national cancer institute common terminology criteria for adverse events, version 4.0 (nci ctcae, v4.0) * history of systemic anti-cancer therapy after the diagnosis of metastatic breast cancer (mbc) or for recurrent locally advanced disease, with the exception of prior hormonal regimens for recurrent locally advanced disease or mbc * an interval of \< 12 months after the last dose of vinca alkaloid or taxane chemotherapy (i.e., for treatment of early stage, non-metastatic disease) * hormonal therapy \< 7 days prior to randomization * trastuzumab \< 21 days prior to randomization * lapatinib \</= 14 days prior to randomization * prior trastuzumab emtansine therapy * treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization * history of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage i uterine cancer, or other malignancies with an expected curative outcome * current chronic daily treatment with corticosteroids (dose \> 10 mg/day methylprednisone equivalent) * history of intolerance (including grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, docetaxel or paclitaxel * known hypersensitivity any of the study drugs, including excipients, or any drugs formulated in polysorbate 80