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.

1 - 42 . (canceled) 
     
     
         43 . A method of treating early-stage HER2-positive breast cancer in a patient comprising administering Pertuzumab, Trastuzumab, and carboplatin-based chemotherapy to the patient with the early-stage breast cancer. 
     
     
         44 . The method of  claim 43 , wherein the carboplatin-based chemotherapy comprises Docetaxel and Carboplatin. 
     
     
         45 . The method of  claim 43 , wherein the Pertuzumab is administered concurrently with the carboplatin-based chemotherapy. 
     
     
         46 . The method of  claim 43 , wherein Pertuzumab administration does not increase cardiac toxicity relative to administration without Pertuzumab. 
     
     
         47 . The method of  claim 43 , which comprises neoadjuvant or adjuvant therapy. 
     
     
         48 . The method of  claim 43 , wherein the early-stage breast cancer is >2 cm in diameter. 
     
     
         49 . The method of  claim 43 , wherein the early-stage breast cancer has not spread beyond the breast or the axillary lymph nodes. 
     
     
         50 . The method of  claim 43 , wherein the early-stage breast cancer is locally advanced or inflammatory breast cancer. 
     
     
         51 . The method of  claim 43 , wherein the patient has no metastases. 
     
     
         52 . The method of  claim 43 , wherein the early-stage breast cancer is estrogen receptor (ER) and progesterone receptor (PR) negative. 
     
     
         53 . The method of  claim 43 , wherein the neoadjuvant therapy results in a pathological complete response (pCR) in the patient. 
     
     
         54 . The method of  claim 53 , wherein the neoadjuvant treatment comprises Docetaxel/Carboplatin/Trastuzumab (TCH)+Pertuzumab (P) for 6 cycles. 
     
     
         55 . The method of  claim 54 , wherein the neoadjuvant treatment results in pathological complete response (pCR) rate greater than pCR rate with Fluorouracil/Epirubicin/Cyclophosphamide (FEC), Trastuzumab (H), and Pertuzumab (P) for 3 cycles followed by 3 cycles of Docetaxel (T), H, and P (FEC+H+P×3→T+P+H×3) and than pCR rate with FEC for 3 cycles followed by 3 cycles of T, H, and P (FEC×3→T+P+H×3). 
     
     
         56 . A method of treating a HER2-positive 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. 
     
     
         57 . The method of  claim 56 , further comprising administering 420 mg of Pertuzumab every 3 weeks after the re-administered 840 mg dose. 
     
     
         58 . The method of  claim 56 , wherein the cancer patient has HER2-positive breast cancer. 
     
     
         59 . A method of combining two HER2 antibodies to treat HER2-positive breast cancer without increasing cardiac toxicity in a HER2-positive breast cancer patient with a left ventricular ejection fraction (LVEF) of ≤50% pre-treatment, comprising administering Pertuzumab, Trastuzumab, and chemotherapy to the patient, and measuring cardiac toxicity in the patient for incidence of symptomatic left ventricular systolic dysfunction (LVSD), congestive heart failure (CHF), or decrease in left ventricular ejection fraction (LVEF), wherein the cardiac toxicity is not increased compared to cardiac toxicity in a patient treated with Trastuzumab and the chemotherapy. 
     
     
         60 . The method of  claim 59 , wherein the breast cancer is metastatic breast cancer. 
     
     
         61 . The method of  claim 59 , wherein the breast cancer is metastatic or locally recurrent, unresectable breast cancer, or de novo Stage IV disease. 
     
     
         62 . The method of  claim 59 , wherein the chemotherapy comprises taxane. 
     
     
         63 . The method of  claim 62 , wherein the taxane is Docetaxel. 
     
     
         64 . The method of  claim 59 , wherein the cardiac toxicity is LVSD. 
     
     
         65 . The method of  claim 59 , wherein the cardiac toxicity is CHF. 
     
     
         66 . The method of  claim 59 , wherein the cardiac toxicity is decrease in LVEF. 
     
     
         67 . The method of  claim 59 , wherein the patient has not received chemotherapy or biologic therapy for their metastatic disease prior to treatment. 
     
     
         68 . A method of treating a patient with HER2-positive breast cancer comprising administering Pertuzumab, Trastuzumab, and chemotherapy to the patient, and measuring left ventricular ejection fraction (LVEF) in the patient and withholding treatment with pertuzumab and trasutuzmab for at least 3 weeks if the patient has a drop in LVEF to less than 40%, or a LVEF of 40% to 45% with a 10% or greater absolute decrease below pre-treatment value. 
     
     
         69 . The method of  claim 68 , further comprising resuming treatment with pertuzumab if the LVEF has recovered to greater than 45%, or to 40% to 45% associated with less than a 10% absolute decrease below pretreatment value.