Herceptin® adjuvant therapy

Abstract

The present application describes adjuvant therapy of nonmetastatic breast cancer using HERCEPTIN®.

What is claimed is: 
     
         1 . A method of adjuvant therapy comprising administering to a human subject having HER2 positive cancer, following definitive surgery, anthracycline cyclophosphamide (AC) based chemotherapy, followed by administration of an effective amount of (a) an immunoconjugate comprising an anti-ErbB2 antibody that binds to HER2 Domain IV bound by trastuzumab (HERCEPTIN®), wherein the anti-ErbB2 antibody is conjugated to a maytansinoid, and (b) a second anti-ErbB2 antibody, wherein the second anti-ErbB2 antibody is a HER2 dimerization inhibitor. 
     
     
         2 . The method of  claim 1  wherein the anti-ErbB2 antibody conjugated to said maytansinoid is huMAb4D5-8. 
     
     
         3 . The method of  claim 2  wherein the maytansinoid is DM1 having the following structure 
       
         
           
           
               
               
           
         
       
       and wherein the anti-ErbB2 antibody is chemically linked to the maytansinoid via a disulfide or thioether group at “R” shown in the structure. 
     
     
         4 . The method of  claim 3 , wherein the immunoconjugate comprises from 3 to 5 maytansinoid molecules per antibody molecule. 
     
     
         5 . The method of any one of  claims 1  to  3 , wherein the anti-ErbB2 antibody and the maytansinoid are conjugated by a chemical linker selected from N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), N-succinimidyl-4-(2-pyridylthio)pentanoate (SPP) and succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC). 
     
     
         6 . The method of  claim 5 , wherein the anti-ErbB2 antibody and the maytansinoid are conjugated by succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC). 
     
     
         7 . The method of any one of  claims 1 - 4 , wherein the second anti-ErbB2 antibody is pertuzumab. 
     
     
         8 . The method of  claim 6 , wherein the second anti-ErbB2 antibody is pertuzumab. 
     
     
         9 . The method of any one of  claims 1 - 4 , wherein the HER2 positive cancer is HER2 positive breast cancer. 
     
     
         10 . The method of  claim 9 , wherein the HER2 positive breast cancer is nonmetastatic HER2 positive breast cancer. 
     
     
         11 . The method of  claim 7 , wherein the HER2 positive cancer is HER2 positive breast cancer. 
     
     
         12 . The method of  claim 11 , wherein the HER2 positive breast cancer is nonmetastatic HER2 positive breast cancer.