Gene detection assay for improving the likelihood of an effective response to an ErbB antagonist cancer therapy

Abstract

The invention provides a method for more effective treatment of patients susceptible to or diagnosed with tumors overexpressing ErbB, as determined by a gene amplification assay, with an ErbB antagonist. Such method comprises administering a cancer-treating dose of the ErbB antagonist, preferably in addition to chemotherapeutic agents, to a subject in whose tumor cells ErbB has been found to be amplified e.g., by fluorescent in situ hybridization. ErbB antagonists described include an anti-HER2 antibody. Pharmaceutical packaging for providing the components for such treatment is also provided.

What is claimed:  
     
         1 . A method for increasing likelihood of effectiveness of an ErbB antagonist cancer treatment, which method comprises administering a cancer treating dose of the ErbB antagonist to a subject, wherein an erbB gene in tumor cells in a tissue sample from the subject has been found to be amplified.  
     
     
         2 . The method according to  claim 1 , wherein the ErbB is a HER2 protein.  
     
     
         3 . The method according to  claim 2 , wherein the cancer is breast cancer.  
     
     
         4 . The method according to  claim 3 , wherein the subject has been found to have a 0 or 1+ score by immunohistochemistry on a formaldehyde-fixed tissue sample.  
     
     
         5 . The method according to  claim 1 , wherein the ErbB antagonist is an anti-ErbB antibody.  
     
     
         6 . The method according to  claim 5 , wherein the ErbB is HER2, and the antibody is recombinant human monoclonal antibody (rhuMAb) 4D5.  
     
     
         7 . The method according to  claim 1  wherein the erbB gene amplification is detected by detecting fluorescence of a fluorescent-labeled nucleic acid probe hybridized to the gene.  
     
     
         8 . The method according to  claim 7 , wherein the erbB gene is a her2 gene.  
     
     
         9 . The method according to  claim 1 , which further comprises administering a cancer treating dose of a chemotherapeutic drug.  
     
     
         10 . The method according to  claim 9 , wherein the ErbB is HER2 and the chemotherapeutic drug is a taxoid.  
     
     
         11 . The method according to  claim 1  wherein the likelihood of effectiveness increases by about 30%.  
     
     
         12 . A method for increasing likelihood of effectiveness of an anti-HER2 antibody to treat cancer, which method comprises administering a cancer treating dose of the anti-HER2 antibody to the subject, wherein a her2 gene in tumor cells in a tissue sample from the subject have been found to be amplified.  
     
     
         13 . The method according to  claim 12 , wherein the subject has been found to have a 0 or 1+ score by immunohistochemistry on a formaldehyde-fixed tissue sample.  
     
     
         14 . The method according to  claim 12 , which further comprises administering a cancer treating dose of a taxoid.  
     
     
         15 . A pharmaceutical package comprising: 
 (a) a container comprising an ErbB antagonist for treating a cancer; and    (b) instructions to administer the ErbB antagonist to a subject if an erbB gene in tumor cells in a tissue sample from the subject is amplified.    
     
     
         16 . The package of  claim 15 , wherein the ErbB antagonist is an antibody.  
     
     
         17 . The package of  claim 16 , wherein the antibody is an anti-HER2 antibody.  
     
     
         18 . The package of  claim 17 , wherein the anti-HER2 antibody is rhuMAb 4D5 (Herceptin®).  
     
     
         19 . The package of  claim 15 , wherein the instructions further comprise directions to administer a chemotherapeutic drug in combination with the ErbB antagonist.  
     
     
         20 . The package of  claim 19 , wherein the chemotherapeutic drug is a taxoid.  
     
     
         21 . A method for identifying a patient disposed to respond favorably to an ErbB antagonist for treating cancer, which method comprises detecting erbB gene amplification in tumor cells in a tissue sample from the patient.  
     
     
         22 . The method according to  claim 21 , wherein the subject has been found to have a 0 or 1+ score by immunohistochemistry on a formaldehyde-fixed tissue sample.  
     
     
         23 . The method according to  claim 21 , wherein the erbB is her2.