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; combining two HER2 antibodies to treat HER2-positive cancer without increasing cardiac toxicity; and treating HER2-positive cancer by co-administering a mixture of Pertuzumab and Trastuzumab from the same intravenous bag.

Description

[0001]This is a continuation application which claims priority under 35 USC §120 to non-provisional application Ser. No. 13 / 649,591, filed on Oct. 11, 2012, which claims the benefit under 35 USC §119(e) of U.S. Provisional Application Ser. No. 61 / 547,535, filed on Oct. 14, 2011, U.S. Provisional Application Ser. No. 61 / 567,015, filed on Dec. 5, 2011, U.S. Provisional Application Ser. No. 61 / 657,669, filed on Jun. 8, 2012, U.S. Provisional Application Ser. No. 61 / 682,037, filed on Aug. 10, 2012 and U.S. Provisional Application Ser. No. 61 / 694,584, filed on Aug. 29, 2012, which are incorporated by reference in entirety.FIELD OF THE INVENTION[0002]The present invention concerns uses for and articles of manufacture including Pertuzumab, a first-in-class HER2 dimerization inhibitor.[0003]In particular, the invention concerns extending progression free survival in a HER2-positive breast cancer patient population; combining two HER2 antibodies to treat HER2-positive cancer without increasi...

AI Technical Summary

Benefits of technology

[0017]In a first aspect, the invention concerns 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 (e.g. taxane, such as Docetaxel) to the patients in the population. Optionally the method results in an objective response rate of 80% or more in the patients in the population. The the breast cancer is optionally metastatic or locally recurrent, unresectable breast cancer, or de novo Stage IV disease. In one embodiment, the patients in the population: have not received previous treatment or have relapsed after adjuvant therapy, have a left ventricular ejection fraction (LVEF) of ≧50% at baseline, and / or have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Optionally, the HER2-positive breast cancer is defined as immunohistochemistry (IHC) 3+ and / or fluorescence in situ hybridization (FISH) amplification ratio≧2.0. Optionally, the method reduces the risk of death by about 34% or more relative to a patient treated with Trastuzumab and the chemotherapy.

[0038]In a particular aspect, the invention concerns a method of treating HER2-positive non-resectable or metastatic adenocarcinoma of the stomach or gastroesophageal junction in a human patient who did not receive prior chemotherapy for metastatic disease, except prior adjuvant or neoadjuvant therapy completed more than six months before the current treatment, comprising administering Pertuzumab, Trastuzumab, cisplatin, and capecitabine and / or fluorouracil (5-FU) to the patient in an amount to improve progression free survival (PFS) and / or overall survival (OS), wherein the patient has an ECOG PS of 0-1. In a particular embodiment, the patient did not receive prior treatment with a platin.

[0039]In another aspect, the invention concerns a method of improving progression free survival in a patient with HER2-positive non-resectable or metastatic adenocarcinoma of the stomach or gastroesophageal junction comprising administering Pertuzumab to the patient in combination with Trastuzumab and chemotherapy.

Problems solved by technology

Pertuzumab blockade of the formation of HER2-HER3 heterodimers in tumor cells has been demonstrated to inhibit critical cell signaling, which results in reduced tumor proliferation and survival (Agus et al.

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