a study of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with her2-positive breast cancer who have residual tumor in the breast or axillary lymph nodes following preoperative therapy (katherine)

Conditions: Breast Cancer

Summary: this 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with her2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. radiotherapy and/or hormone therapy will be given in addition if indicated.


Eligibility criteria:
inclusion criteria: * adult patient, \>/= 18 years of age * her2-positive breast cancer * histologically confirmed invasive breast carcinoma * clinical stage t1-4/n0-3/m0 at presentation (patients with t1a/bn0 tumors will not be eligible) * completion of preoperative systemic chemotherapy and her2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy * adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol * pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy * an interval of no more than 12 weeks between the date of surgery and the date of randomization * known hormone-receptor status * eastern cooperative oncology group (ecog) performance status 0 or 1 * adequate hematologic, renal and liver function * screening left ventricular ejection fraction (lvef) \>/= 50% on echocardiogram (echo) or multiple-gated acquisition (muga) after receiving neoadjuvant chemotherapy and no decrease in lvef by more than 15% absolute points from the pre-chemotherapy lvef. or, if pre-chemotherapy lvef was not assessed, the screening lvef must be \>/= 55% after completion of neoadjuvant chemotherapy. * for women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined 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 * documentation of hepatitis b virus and hepatitis c virus serology is required exclusion criteria: * stage iv (metastatic) breast cancer * history of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ * evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery * progressive disease during preoperative systemic therapy * treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment * 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 non-breast malignancies with a similar outcome to those mentioned above * patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons * current nci ctcae (version 4.0) grade \>/= 2 peripheral neuropathy * history of exposure to the following cumulative doses of anthracyclines: doxorubicin \> 240 mg/m2; epirubicin or liposomal doxorubicin-hydrochloride (myocet®) \> 480 mg/m2; for other anthracyclines, exposure equivalent to doxorubicin \> 240 mg/m2 * cardiopulmonary dysfunction as defined by protocol * prior treatment with trastuzumab emtansine * current severe, uncontrolled systemic disease * pregnant or lactating women * any known active liver disease, e.g. due to hbv, hcv, autoimmune hepatic disorders, or sclerosing cholangitis * concurrent serious uncontrolled infections requiring treatment or known infection with hiv * history of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product