a study of trastuzumab emtansine (t-dm1) sequentially with anthracycline-based chemotherapy, as adjuvant or neoadjuvant therapy for patients with early stage herceptin (her)2-positive breast cancer

Conditions: Breast Cancer

Summary: this single-arm open-label study assessed the safety, feasibility, and efficacy of trastuzumab emtansine (t-dm1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early her2-positive breast cancer. patients received t-dm1 3.6 mg/kg intravenously on day 1 of each 3-week cycle, for up to 17 cycles.


Eligibility criteria:
inclusion criteria: * adult patients ≥ 18 years of age. * locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive breast cancer documented at a local laboratory (patients with inflammatory breast cancer must be able to have a core needle biopsy). * herceptin (her)2-positive tumor, confirmed by central testing using immunohistochemistry (ihc) and in situ hybridization (ish) methods. * willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (ac) or 5-fluorouracil (fu)/epirubicin/ cyclophosphamide (fec) in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment. * for women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or 2 effective forms of non-hormonal contraception by the patient and/or partner. contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. male patients should use condoms for the duration of the study. specific country requirements will be followed. * negative results of serum pregnancy test for premenopausal women of reproductive capacity and for women \< 12 months after menopause. * patients may enroll before or after ac/fec chemotherapy has completed. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * adequate hematologic, biochemistry, and cardiac assessments. exclusion criteria: * stage iv breast cancer or bilateral breast cancer. * pregnant or breastfeeding women. * history of other malignancy within the previous 5 years, except contralateral breast cancer and ductal carcinoma in situ (dcis)/lobular carcinoma in situ (lcis), appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage i uterine cancer, or other cancers with outcome similar to those mentioned above. * radiation therapy, immunotherapy, or biotherapy within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated \> 5 years before study enrollment is allowed. patients receiving ac/fec in a similar fashion to the study treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be allowed to enroll in the study after the completion of their ac/fec. no other prior history of cardiotoxic chemotherapy is allowed. * active cardiac history. * current chronic daily treatment with oral corticosteroids or equivalent. * patients with severe dyspnea at rest or requiring supplementary oxygen therapy. * active, unresolved infections at screening. * human immunodeficiency virus (hiv), hepatitis b virus (hbv), or hepatitis c virus (hcv) infection. * major surgery within 4 weeks before enrollment that is unrelated to the breast cancer. * patients for whom concomitant radiotherapy + t-dm1 may be contraindicated yet radiation therapy is planned. * known hypersensitivity to any of the study drugs or derivatives, including murine proteins. * grade ≥ 2 peripheral neuropathy at baseline.