Extending time to disease progression or survival in cancer patients

Abstract

The present application describes extending time to disease progression or survival in a cancer patient, where the patient's cancer displays HER activation, by treating the patient with a HER dimerization inhibitor, such as pertuzumab.

1 . A method for extending time to disease progression (TTP) or survival in a cancer patient comprising administering a HER dimerization inhibitor to the patient in an amount which extends TTP or survival in the patent, wherein the patient's cancer displays HER activation. 
     
     
         2 . The method of  claim 1  wherein the HER dimerization inhibitor is a HER2 dimerization inhibitor. 
     
     
         3 . The method of  claim 1  wherein the HER dimerization inhibitor inhibits HER heterodimerization. 
     
     
         4 . The method of  claim 1  wherein the patient's cancer displays HER2 activation. 
     
     
         5 . The method of  claim 1  wherein the patient's cancer displays HER2 phosphorylation. 
     
     
         6 . The method of  claim 5  wherein the patient's cancer displays HER2 phosphorylation as evaluated in a phospho-ELISA assay. 
     
     
         7 . The method of  claim 1  wherein the patient's cancer displays HER2 activation as evaluated by gene expression profiling. 
     
     
         8 . The method of  claim 1  wherein the HER dimerization inhibitor is an antibody. 
     
     
         9 . The method of  claim 8  wherein the antibody binds to a HER receptor selected from the group consisting of EGFR, HER2, and HER3. 
     
     
         10 . The method of  claim 9  wherein the antibody binds to HER2. 
     
     
         11 . The method of  claim 10  wherein the HER2 antibody binds to Domain II of HER2 extracellular domain. 
     
     
         12 . The method of  claim 11  wherein the antibody binds to a junction between domains I, II and III of HER2 extracellular domain. 
     
     
         13 . The method of  claim 12  wherein the HER2 antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively. 
     
     
         14 . The method of  claim 13  wherein the HER2 antibody is pertuzumab. 
     
     
         15 . The method of  claim 8  wherein the HER antibody is a naked antibody. 
     
     
         16 . The method of  claim 8  wherein the HER antibody is an intact antibody. 
     
     
         17 . The method of  claim 8  wherein the HER antibody is an antibody fragment comprising an antigen binding region. 
     
     
         18 . The method of  claim 1  wherein the cancer is selected from the group consisting of ovarian cancer, peritoneal cancer, fallopian tube cancer, metastatic breast cancer (MBC), non-small cell lung cancer (NSCLC), prostate cancer, and colorectal cancer. 
     
     
         19 . The method of  claim 18  wherein the cancer is ovarian, peritoneal, or fallopian tube cancer. 
     
     
         20 . The method of  claim 18  wherein the cancer is advanced, refractory or recurrent ovarian cancer. 
     
     
         21 . The method of  claim 1  wherein the HER dimerization inhibitor is administered as a single anti-tumor agent. 
     
     
         22 . The method of  claim 1  comprising administering a second therapeutic agent to the patient. 
     
     
         23 . The method  claim 22  wherein the second therapeutic agent is selected from the group consisting of chemotherapeutic agent, 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. 
     
     
         24 . The method of  claim 23  wherein the second therapeutic agent is a chemotherapeutic agent. 
     
     
         25 . The method of  claim 24  wherein the chemotherapeutic agent is an antimetabolite chemotherapeutic agent. 
     
     
         26 . The method of  claim 25  wherein the antimetabolite chemotherapeutic agent is gemcitabine. 
     
     
         27 . The method of  claim 22  wherein the second therapeutic agent is trastuzumab, erlotinib, or bevacizumab. 
     
     
         28 . The method of  claim 1  wherein TTP is extended. 
     
     
         29 . The method of  claim 1  wherein survival is extended. 
     
     
         30 . The method of  claim 1  wherein administration of the HER dimerization inhibitor extends TTP or survival at least about 20% more than TTP or survival achieved by administering an approved anti-tumor agent to the cancer patient. 
     
     
         31 . A method for extending time to disease progression (TTP) or survival in a patient with ovarian, peritoneal, or fallopian tube cancer comprising administering pertuzumab to the patient in an amount which extends TTP or survival in the patent, wherein the patient's cancer displays HER2 activation. 
     
     
         32 . The method of  claim 31  wherein patient has ovarian cancer. 
     
     
         33 . The method of  claim 31  wherein the patient has advanced, refractory or recurrent cancer. 
     
     
         34 . The method of  claim 31  wherein administration of pertuzumab to the patient extends TTP or survival at least about 20% more than TTP or survival achieved by administering topotecan or liposomal doxorubicin to the patient. 
     
     
         35 . The method of  claim 31  further comprising administering a chemotherapeutic agent to the patient. 
     
     
         36 . The method of  claim 35  wherein the chemotherapeutic agent is an antimetabolite chemotherapeutic agent. 
     
     
         37 . The method of  claim 36  wherein the antimetabolite chemotherapeutic agent is gemcitabine.