efficacy study of single agent trastuzumab or lapatinib to treat her2-overexpressing breast cancer

Conditions: Metastatic Breast Cancer

Summary: this study will evaluate the activity of single agent trastuzumab or lapatinib in patients not previously treated for her-2 positive (fish positive) metastatic breast cancer. a companion biological study will assess factors correlated with sensitivity or resistance to either one of the compounds


Eligibility criteria:
inclusion criteria: * women aged 18-75 years * histologically or cytologically confirmed metastatic disease. * her2-overexpression proven by fluorescence in situ hybridization (fish). * availability of paraffin-embedded block of either primitive tumor and/or biopsy of metastases. * no prior chemotherapy for metastatic or locally advanced disease. patients with hormone receptor (oestrogen and/or progesterone) positive breast cancer can be eligible provided that they had received only one line of hormonal therapy for metastatic disease. * for patients undergoing hormonal therapy for metastatic disease, disease progression must be confirmed according to recist criteria. * at least 20% increase in the sum of longest diameters, or * evidence of new metastatic lesions or progression of pre-existing non-target lesions. * presence of at least one monodimensionally measurable lesion. patients without clinically or radiologically proven evidence of disease are not eligible. * patients with exclusively skin disease are eligible, provided that the disease evolution under treatment can be photographically documented. * patients with involvement of ncs, besides presence of measurable lesions, are eligible provided that: * brain lesion/s has/have been radically resected; * brain lesion/s has/have obtained complete remission following radiation therapy. complete remission must be documented by tc or rmn. * at least 4-week interval from end of radiotherapy, hormono- or immunotherapy and enrollment in this study. * ecog ps \</= 2 and life expectancy of at least 6 months. * liver metastases involving \< 30% of liver volume. * adequate hematopoietic, liver and renal function * written informed consent. * patients with childbearing potential must have negative pregnancy test and must use adequate contraceptive measures during treatment. * prior treatment with trastuzumab as adjuvant therapy is permitted provided that it was completed at least 12 months prior enrollment in this study. exclusion criteria: * prior chemotherapy for metastatic disease. * active pregnancy or breastfeeding. * previous treatment with lapatinib. * previous therapy with mono- or policlonal antibodies for metastatic disease. * patients with bone involvement or pleural effusion/ascites as unique localization of disease. * patients with dyspnea due to presence of disease (lymphangitis) or requiring oxygen therapy. * patients with clinically evident hearth disease and/or active infectious diseases. * patients with not resected or not irradiated brain and/or leptomeningeal metastases. * prior or actual concurrent neoplasms, with the exception of adequately treated carcinoma della cervice uterina and basal cell or squamocellular carcinoma of the skin. * patients with uncontrolled serious illnesses that may compromise the compliance of the patient to the treatment. * previous allergic reactions towards any excipient in the composition of trastuzumab or lapatinib. * use of any experimental drug within 4 weeks prior initiation of study treatment. * women with childbearing potential who refuse to use adequate contraceptive measures. * patients unable to give written informed consent or are not compliant with treatment. * patients with great tumor involvement (\> 30% dof hepatic volume, etc).

Keywords: breast cancer her2 trastuzumab lapatinib her2 gene-amplification