Combination therapy for the treatment of ovarian cancer

Abstract

This invention concerns methods of treating a patient diagnosed with a platinum-resistant ovarian cancer comprising administering to said patient an effective amount of an anti-VEGF antibody and a chemotherapeutic.

1 . A method of treating a patient diagnosed with a platinum-resistant ovarian cancer comprising administering to said patient an effective amount of an anti-VEGF antibody and a chemotherapeutic, wherein said patient received two or fewer prior anti-cancer regimens, wherein said treatment prolongs said patient's median progression-free survival time as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         2 . The method of  claim 1 , wherein said platinum-resistant ovarian cancer is an epithelial ovarian cancer (EOC), a fallopian tube carcinoma (FTC), or a primary peritoneal carcinoma (PPC). 
     
     
         3 . The method of  claim 1 , wherein said patient is not refractory to previous platinum treatment. 
     
     
         4 . The method of  claim 1 , wherein said patient has measurable disease according to RECIST 1.0 or CA-125 assessable disease according to the GCIG criteria. 
     
     
         5 . The method of  claim 1 , wherein said patient has an ECOG performance status of 0-2. 
     
     
         6 . The method of  claim 1 , wherein said patient has a life expectancy of at least 12 weeks. 
     
     
         7 . The method of  claim 1 , wherein said chemotherapeutic is selected from the group consisting of paclitaxel, topotecan or a pegylated liposomal doxorubicin (PLD). 
     
     
         8 . The method of  claim 7 , wherein said effective amount of said paclitaxel is administered at 80 mg/m 2  as a 1 hour intravenous infusion on days 1, 8, 15 and 22 q4w. 
     
     
         9 . The method of  claim 7 , wherein said effective amount of said topotecan is administered at 4 mg/m 2  as a 30 minute intravenous infusion on days 1, 8 and 15 q4w. 
     
     
         10 . The method of  claim 7 , wherein said effective amount of said topotecan is administered at 1.25 mg/m 2  as a 30 minute intravenous infusion on days 1 to 5 every three weeks. 
     
     
         11 . The method of  claim 7 , wherein said effective amount of said PLD is administered at 40 mg/m 2  as a 1 mg/min intravenous infusion on day 1 only, then as a 1 hour infusion thereafter, q4w. 
     
     
         12 . The method of  claim 1 , wherein said anti-VEGF antibody binds the A4.6.1 epitope. 
     
     
         13 . The method of  claim 1 , wherein said anti-VEGF antibody is bevacizumab. 
     
     
         14 . The method of  claim 1 , wherein said anti-VEGF antibody comprises a variable heavy chain (VH) and a variable light chain (VL), wherein said VH has an amino acid sequence of SEQ ID NO:2 and said VL has an amino acid sequence of SEQ ID NO:1. 
     
     
         15 . The method of  claim 1 , wherein said effective amount of said anti-VEGF antibody is 10 mg/kg intravenously every two weeks. 
     
     
         16 . The method of  claim 10 , wherein said effective amount of said anti-VEGF antibody is 15 mg/kg intravenously every three weeks. 
     
     
         17 . The method of  claim 15 , wherein said effective amount of said anti-VEGF antibody is administered initially intravenously over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes. 
     
     
         18 . The method of  claim 16 , wherein said effective amount of said anti-VEGF antibody is administered initially intravenously over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes. 
     
     
         19 . The method of  claim 1 , wherein said anti-VEGF antibody is administered first to said patient at the first cycle. 
     
     
         20 . The method of  claim 19 , wherein subsequent administrations of said anti-VEGF antibody are either prior to or after said chemotherapeutic. 
     
     
         21 . The method of  claim 1 , wherein said anti-VEGF antibody is administered concurrently with said chemotherapeutic. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 1 , wherein said patient is less than 65 years old. 
     
     
         27 . The method of  claim 1 , wherein said patient is equal to or greater than 65 years old. 
     
     
         28 . The method of  claim 1 , wherein said patient has a platinum free interval (PFI) of less than 3 months. 
     
     
         29 . The method of  claim 1 , wherein said patient has a PFI of 3 to 6 months. 
     
     
         30 . The method of  claim 1 , wherein said patient has abdominal ascites. 
     
     
         31 . The method of  claim 1 , wherein said patient does not have abdominal ascites. 
     
     
         32 . The method of  claim 1 , wherein said treatment further improves said patient's objective response rate (ORR) as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         33 . The method of  claim 32 , wherein said ORR is improved by at least 1.5 fold as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         34 . The method of  claim 32 , wherein said ORR is improved by at least 2 fold as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         35 . The method of  claim 32 , wherein said ORR is improved to about 30.9% as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 33 , wherein said chemotherapeutic is paclitaxel. 
     
     
         40 . The method of  claim 33 , wherein said chemotherapeutic is pegylated liposomal doxorubicin (PLD). 
     
     
         41 . The method of  claim 34 , wherein said chemotherapeutic is topotecan. 
     
     
         42 . A kit comprising an anti-VEGF antibody binding essentially to epitope A4.6.1, a chemotherapeutic and a package insert or label with instructions to treat a patient diagnosed with a platinum-resistant ovarian cancer comprising administering to said patient an effective amount of an anti-VEGF antibody and a chemotherapeutic, wherein said patient received two or fewer prior anti-cancer regimens, wherein said treatment prolongs said patient's median progression-free survival time as compared to a platinum-resistant ovarian cancer patient receiving said chemotherapeutic alone. 
     
     
         43 . The kit of  claim 42 , wherein said platinum-resistant ovarian cancer is an epithelial ovarian cancer (EOC), a fallopian tube carcinoma (FTC), or a primary peritoneal carcinoma (PPC). 
     
     
         44 . The kit in  claim 42 , wherein said anti-VEGF antibody is bevacizumab and said chemotherapeutic is selected from the group consisting of paclitaxel, topotecan or a pegylated liposomal doxorubicin (PLD). 
     
     
         45 . A method of promoting administration of an anti-VEGF antibody binding essentially to epitope A4.6.1, and a chemotherapeutic to treat platinum-resistant ovarian cancer in a patient, wherein said promotion is by written material. 
     
     
         46 . The method of  claim 45 , wherein said anti-VEGF antibody is bevacizumab, and said chemotherapeutic is selected from the group consisting of paclitaxel, topotecan or a pegylated liposomal doxorubicin (PLD). 
     
     
         47 . The method of  claim 45 , wherein said written material is a package insert or label that accompanies a commercial formulation of said anti-VEGF antibody and said chemotherapeutic.