Uses for and article of manufacture including her2 dimerization inhibitor pertuzumab

Abstract

The present application describes uses for Pertuzumab, a first-in-class HER2 dimerization inhibitor. In particular, the application describes methods for extending progression free survival in a HER2-positive breast cancer patient population; and combining two HER2 antibodies to treat HER2-positive cancer without increasing cardiac toxicity.

What is claimed is: 
     
         1 . A method for extending progression free survival in a HER2-positive breast cancer patient population by 6 months or more comprising administering Pertuzumab, Trastuzumab and chemotherapy to the patients in the population. 
     
     
         2 . The method of  claim 1  which results in an objective response rate of 80% or more in the patients in the population. 
     
     
         3 . The method of  claim 1  wherein the chemotherapy comprises taxane. 
     
     
         4 . The method of  claim 3  wherein the taxane is Docetaxel. 
     
     
         5 . The method of  claim 1  wherein the breast cancer is metastatic or locally recurrent, unresectable breast cancer, or de novo Stage IV disease. 
     
     
         6 . The method of  claim 1  wherein the patients in the population have not received previous treatment or have relapsed after adjuvant therapy. 
     
     
         7 . The method of  claim 1  wherein the HER2-positive breast cancer is defined as immunohistochemistry (IHC) 3+ and/or fluorescence in situ hybridization (FISH) amplification ratio ≥2.0. 
     
     
         8 . The method of  claim 1  wherein the patients in the population have a left ventricular ejection fraction (LVEF) of ≥50% at baseline. 
     
     
         9 . The method of  claim 1  wherein the patients in the population have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 
     
     
         10 . A method of combining two HER2 antibodies to treat HER2-positive cancer without increasing cardiac toxicity in a HER2-positive cancer patient population, comprising administering Pertuzumab, Trastuzumab, and chemotherapy to the patients in the population. 
     
     
         11 . The method of  claim 10  wherein cardiac toxicity in the patient population is monitored for incidence of symptomatic left ventricular systolic dysfunction (LVSD) or congestive heart failure (CHF), or decrease in left ventricular ejection fraction (LVEF). 
     
     
         12 . The method of  claim 10  wherein the HER2-positive cancer is breast cancer. 
     
     
         13 . The method of  claim 10  wherein the breast cancer is metastatic or locally recurrent, unresectable breast cancer, or de novo Stage IV disease. 
     
     
         14 . An article of manufacture comprising a vial with Pertuzumab therein and a package insert, wherein the package insert provides the safety data in Table 3 or Table 4. 
     
     
         15 . The article of manufacture of  claim 14  wherein the package insert provides the efficacy data in Table 2, Table 5,  FIG. 8 , or  FIG. 10 . 
     
     
         16 . The article of manufacture of  claim 14  wherein the vial is a single-dose vial containing about 420 mg of Pertuzumab. 
     
     
         17 . A method for making an article of manufacture comprising packaging together a vial with Pertuzumab therein and a package insert, wherein the package insert provides the safety data in Table 3 or Table 4. 
     
     
         18 . A method of ensuring safe and effective use of Pertuzumab comprising packaging together a vial with Pertuzumab therein and a package insert, wherein the package insert provides the safety data in Table 3 or Table 4 and the efficacy data in Table 2, Table 5,  FIG. 8 , or  FIG. 10 . 
     
     
         19 . A method of treating early-stage HER2-positive breast cancer comprising administering Pertuzumab, Trastuzumab, and chemotherapy to a patient with the breast cancer, wherein the chemotherapy comprises anthracycline-based chemotherapy, or carboplatin-based chemotherapy. 
     
     
         20 . The method of  claim 19  wherein chemotherapy comprises anthracycline-based chemotherapy which comprises 5-FU, epirubicin, and cyclophosphamide (FEC). 
     
     
         21 . The method of  claim 20  wherein the Pertuzmab is administered concurrently with the anthracycline-based chemotherapy. 
     
     
         22 . The method of  claim 19  wherein the chemotherapy comprises carboplatin-based chemotherapy which comprises Docetaxel and Carboplatin. 
     
     
         23 . The method of  claim 22  wherein the Pertuzmab is administered concurrently with the carboplatin-based chemotherapy. 
     
     
         24 . The method of  claim 19  wherein Pertuzumab administration does not increase cardiac toxicity relative to the treatment without Pertuzumab. 
     
     
         25 . The method of  claim 19  which comprises neoadjuvant or adjuvant therapy. 
     
     
         26 . A method of treating HER2-positive breast cancer in a patient comprising administering Pertuzumab, Trastuzumab, and aromatase inhibitor to the patient. 
     
     
         27 . The method of  claim 26  wherein the aromatase inhibitor is anastrazole or letrozole. 
     
     
         28 . The method of  claim 26  wherein the breast cancer is hormone receptor-positive advanced breast cancer. 
     
     
         29 . The method of  claim 28  wherein the hormone receptor is estrogen receptor (ER) and/or progesterone receptor (PgR). 
     
     
         30 . The method of  claim 26  wherein the patient has not previously received systemic nonhormonal anticancer therapy in the metastatic setting. 
     
     
         31 . The method of  claim 26  wherein the patient receives induction chemotherapy. 
     
     
         32 . The method of  claim 31  wherein the induction chemotherapy comprises a taxane. 
     
     
         33 . The method of  claim 17  wherein the package insert further comprises the warning box in Example 4. 
     
     
         34 . A method of treating a cancer patient comprising administering to the patient an initial dose of 840 mg of Pertuzumab followed every 3 weeks thereafter by a dose of 420 mg of Pertuzumab, and further comprising re-administering an 840 mg dose of Pertuzumab to the patient if the time between two sequential 420 mg doses is 6 weeks or more. 
     
     
         35 . The method of  claim 34  further comprising administering 420 mg of Pertuzumab every 3 weeks after the re-administered 840 mg dose. 
     
     
         36 . The method of  claim 34  wherein the cancer patient has HER2-positive breast cancer. 
     
     
         37 . The method of  claim 1  which reduces the risk of death by about 34% or more relative to a patient treated with Trastuzumab and the chemotherapy. 
     
     
         38 . The method of  claim 17  wherein the package insert further provides the Overall Survival (OS) efficacy data in Example 9 or Table 14. 
     
     
         39 . A method for treating HER2-positive metastatic or locally recurrent breast cancer in a patient comprising administering Pertuzumab, Trastuzumab and taxoid to the patient, wherein the patient has been previously treated with a Trastuzumab and/or lapatinib as adjuvant or neoadjuvant therapy. 
     
     
         40 . The method of  claim 39  wherein the taxoid is Docetaxel, Paclitaxel, or nab-paclitaxel. 
     
     
         41 . The method of  claim 39  wherein the taxoid is Paclitaxel or nab-paclitaxel. 
     
     
         42 . The method of  claim 39  wherein the patient has been previously treated with Trastuzumab as neoadjuvant therapy.