A Phase II, Randomized Trial With Single Agent Trastuzumab or Lapatinib in Patients With Metastatic HER2-Overexpressing Breast Cancer
- 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
- 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
- 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.
- 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
- Patients with dyspnea due to presence of disease (lymphangitis) or requiring oxygen
- 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
- 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
- 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).