efficacy and safety of trastuzumab emtansine in chinese participants with human epidermal growth factor receptor 2 (her2)-positive locally advanced or metastatic breast cancer

Conditions: Breast Cancer

Summary: this is a phase iii, randomized, multicenter, two-arm, open-label study designed to evaluate the safety and efficacy of trastuzumab emtansine compared with that of lapatinib + capecitabine in chinese participants with her2-positive, unresectable locally advanced breast cancer (labc) or metastatic breast cancer (mbc) who have received prior trastuzumab-based therapy. a total of approximately 350 participants will be enrolled in china. the study will consist of 2 stages. stage 1: eligible participants will be randomized in a 3:1 ratio to receive either trastuzumab emtansine or control (lapatinib + capecitabine). stage 2: after stage 1 is recruited, eligible patients will be enrolled to receive trastuzumab emtansine only.


Eligibility criteria:
inclusion criteria: * aged \>/= 18 years * prospective centrally assessed her2-positive disease (i.e., immunohistochemistry \[ihc\] 3+ and/or gene amplified \[her2 to chromosome 17 \[cep 17\] ratio \>/= 2\]) by in situ hybridization (ish) through use of archival paraffin-embedded tumor tissue * histologically or cytologically confirmed invasive breast cancer (bc): incurable, unresectable labc previously treated with multimodality therapy or mbc * prior treatment for bc in the adjuvant, unresectable locally advanced or metastatic setting must include both: a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent in the adjuvant, unresectable locally advanced or metastatic setting * documented progression of incurable, unresectable labc or mbc, defined by the investigator: progression must occur during or after most recent treatment for labc or mbc or within 6 months after completing adjuvant therapy * measurable and/or non-measurable disease, according the response evaluation criteria in solid tumors (recist) v1.1 definition: cns-only disease excluded * left ventricular ejection fraction (lvef) \>/=50% by either echocardiogram or multiple-gated acquisition * eastern cooperative oncology group (ecog) performance status of 0 or 1 * adequate organ function evidenced by laboratory results within 30 days prior to randomization * for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 7 months after the last dose of study drug * for men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year) and agreement to refrain from donating sperm during the treatment period and for at least 7 months after the last dose of study drug exclusion criteria: * history of treatment with trastuzumab emtansine * prior treatment with lapatinib or capecitabine * peripheral neuropathy of grade \>/= 3 per national cancer institute common terminology criteria for adverse events version 4.0 (nci ctcae v4.0) * history of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage 1 uterine cancer, synchronous or previously diagnosed her2-positive bc, or cancers with a similar curative outcome as those mentioned above * history of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization, except hormone therapy which can be given up to 7 days prior to randomization * history of radiation therapy within 14 days before randomization * brain metastases that are untreated, symptomatic, progressive, or require therapy such as radiation, surgery or corticosteroid therapy to control symptoms from brain metastases within 30 days before randomization * history of exposure to cumulative doses of anthracyclines: doxorubicin \> 500 milligrams per square meter (mg/m\^2), epirubucin \> 720 mg/m\^2, mitoxantrone \> 120 mg/m\^2 * current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) * pregnancy or lactation * currently known active infection with hiv, hepatitis b virus (hbv), or hepatitis c virus (hcv) * presence of conditions that could affect gastrointestinal absorption * history of intolerance (including grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins * known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency * current treatment with sorivudine or its chemically related analogs