Treatment of metastic breast cancer

Abstract

The present invention concerns treatment of previously untreated HER2-positive metastatic breast cancer with a combination of a growth inhibitory HER2 antibody, a HER2 dimerization inhibitor antibody and a taxane. In particular, the invention concerns the treatment of HER2-positive metastatic breast cancer in patients who did not receive prior chemotherapy or biologic therapy with a HER2 antibody binding essentially to epitope 2C4, a HER2 antibody binding essentially to epitope 4D5, and a taxane. The invention further comprises extending survival of such patients by the combination therapy of the present invention. In a preferred embodiment, the treatment involves administration of trastuzumab, pertuzumab and docetaxel.

What is claimed is: 
     
         1 . A method for the treatment of breast cancer, comprising administering to a HER2 positive metastatic breast cancer patient an effective amount of a growth inhibitory HER2 antibody, a HER2 dimerization inhibitor antibody, and a taxane, wherein the patient did not receive prior chemotherapy or biologic therapy for their metastatic breast cancer. 
     
     
         2 . The method of  claim 1  wherein the growth inhibitory HER2 antibody binds to an epitope within Domain IV (SEQ ID NO: 17) of the HER2 amino acid sequence. 
     
     
         3 . The method of  claim 2  wherein the growth inhibitory HER2 antibody binds essentially to epitope 4D5 of HER2. 
     
     
         4 . The method of  claim 1  wherein the HER2 dimerization inhibitor antibody binds HER2 at the junction of domains I, II and III (SEQ ID NOs: 14, 15, and 16). 
     
     
         5 . The method of  claim 4  wherein the HER2 dimerization inhibitor antibody binds essentially to epitope 2C4. 
     
     
         6 . The method of  claim 1  wherein the growth inhibitory and/or the HER2 dimerization inhibitor antibody is an antibody fragment. 
     
     
         7 . The method of  claim 1  wherein the growth inhibitory and/or the HER2 dimerization inhibitor antibody is chimeric, humanized, or human. 
     
     
         8 . The method of  claim 1  wherein the growth inhibitory antibody is trastuzumab, or a fragment thereof, the HER2 dimerization antibody is pertuzumab, or a fragment thereof, and the taxane is docetaxel. 
     
     
         9 . A method for the treatment of breast cancer, comprising administering to a HER2 positive metastatic breast cancer patient an effective amount of a first HER2 antibody binding essentially to epitope 2C4, a second HER2 antibody binding essentially to epitope 4D5, and a taxane, wherein the patient did not receive prior chemotherapy or biologic therapy for their metastatic breast cancer. 
     
     
         10 . The method of  claim 9  wherein the patient is a human patient. 
     
     
         11 . The method of  claim 10  wherein said first and second antibodies are monoclonal antibodies. 
     
     
         12 . The method of  claim 10  wherein at least one of said first and said second antibody is an antibody fragment. 
     
     
         13 . The method of  claim 11  wherein at least one of said first and said second antibody is chimeric humanized, or human. 
     
     
         14 . The method of  claim 10  wherein said first antibody is pertuzumab. 
     
     
         15 . The method of  claim 10  or  claim 14  wherein said second antibody is trastuzumab. 
     
     
         16 . The method of  claim 14  wherein said taxane is docetaxel. 
     
     
         17 . The method of  claim 15  wherein said taxane is docetaxel. 
     
     
         18 . The method of  claim 10  wherein said first and second antibodies and said taxane are administered concurrently. 
     
     
         19 . The method of  claim 10  wherein said first and second antibodies and said taxane are administered consecutively, in any order. 
     
     
         20 . The method of  claim 10  wherein administration of the first antibody precedes administration of the second antibody and the taxane. 
     
     
         21 . The method of  claim 16  wherein at least one of the pertuzumab and the trastuzumab is a naked antibody. 
     
     
         22 . The method of  claim 16  wherein at least one of the pertuzumab and the trastuzumab is an intact antibody. 
     
     
         23 . The method of  claim 16  wherein administration of the pertuzumab, trastuzumab and docetaxel results in a synergistic effect. 
     
     
         24 . The method of  claim 16  wherein administration of the pertuzumab, trastuzumab and docetaxel extends survival of the human patient relative to treatment in the absence of at least one of pertuzumab, trastuzumab and docetaxel. 
     
     
         25 . The method of  claim 24  wherein progression free survival (PFS) is extended. 
     
     
         26 . The method of  claim 24  wherein overall survival (OS) is extended. 
     
     
         27 . The method of  claim 10  further comprising the administration of a further therapeutic agent selected from the group consisting of chemotherapeutic agent, a different HER antibody, antibody directed against a tumor associated antigen, anti-hormonal compound, cardioprotectant, cytokine, EGFR-targeted drug, anti-angiogenic agent, tyrosine kinase inhibitor, COX inhibitor, non-steroidal anti-inflammatory drug, farnesyl transferase inhibitor, antibody that binds oncofetal protein CA 125, HER2 vaccine, HER targeting therapy, Raf or ras inhibitor, liposomal doxorubicin, topotecan, taxane, dual tyrosine kinase inhibitor, TLK286, EMD-7200, a medicament that treats nausea, a medicament that prevents or treats skin rash or standard acne therapy, a medicament that treats or prevents diarrhea, a body temperature-reducing medicament, and a hematopoietic growth factor.