Gene detection assay for improving the likelhood of an effective response to an ErbB antagonist cancer therapy

a gene detection and cancer technology, applied in the field of cancer treatment, can solve the problems of false negative, dilution of malignant cells, and loss of tissue architecture, and achieve the effects of accurate selection basis, high expression, and greater likelihood of respons

a gene detection and cancer technology, applied in the field of cancer treatment, can solve the problems of false negative, dilution of malignant cells, and loss of tissue architecture, and achieve the effects of accurate selection basis, high expression, and greater likelihood of respons

US20060228745A1Inactive Publication Date: 2006-10-12GENENTECH INC
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Examples

Experimental program
Comparison scheme
Effect test

example 1

Concordance Between the Clinical Trials Assay (CTA) and Fluorescence In Situ Hybridization (FISH) in the Herceptin® Pivotal Trials

[0088] Overexpression of HER2 at the 2+ or 3+ level by immunohistochemistry (IHC) was required for enrollment in the pivotal Herceptin® metastatic breast cancer trials. The Clinical Testing Assay (CTA) involves two separate IHC assays performed with either monoclonal antibodies 4D5 (after protease digestion of the formalin fixed sample) or CB11 (after heat treatment of the formalin fixed sample). Subjects were eligible if either assay was scored at 2+ or 3+. If both were performed, the final score was the higher of the two results.

[0089] Concordance between the CTA and another IHC, HercepTest (HT), is 79%. This was the basis for FDA approval of HT to aid in the selection of patients for Herceptin therapy.

[0090] This Example describes a similar concordance study, utilizing clinical material submitted for screening for the Herceptin® pivotal trials, that...

example 2

FISH / Clinical Outcome Study

[0094] This example links the results from three Herceptin® Trials with FISH status. In this study, 805 subjects were selected at random from all three trials. Of these, 167 lacked slides. Another 78 assays (9.7%) failed. Thus, formalin-fixed cut sections stored between 2.5 and 4.5 years from 540 subjects provided the sample pool for this study. There were no imbalances in demographics or prognostic indicators in these samples. Results are reported for different treatment groups.

[0095] Correlation of FISH status with response was evaluated for patients who received Herceptin® as a second or third line therapy. These data are reported for 2+ and 3+ (by CTA) subjects in Table 2.

TABLE 2FISH / Response with single agent Herceptin ®, 2nd or 3rd lineTherapy, 2+ / 3+ CombinedFISH+FISH−Response21 0No response8437response rate20%  0%(12.5-27.5%)(0.7%)

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Abstract

The invention provides a method for more effective treatment of patients susceptible to or diagnosed with tumors overexpressing ErbB, as determined by a gene amplification assay, with an ErbB antagonist. Such method comprises administering a cancer-treating dose of the ErbB antagonist, preferably in addition to chemotherapeutic agents, to a subject in whose tumor cells ErbB has been found to be amplified e.g., by fluorescent in situ hybridization. ErbB antagonists described include an anti-HER2 antibody. Pharmaceutical packaging for providing the components for such treatment is also provided.

Description

[0001] This is a divisional application of non-provisional application Ser. No.09 / 863,101 filed on May 18, 2001, which claims priority under 35 U.S.C. § 119(e) to provisional application Ser. No. 60 / 205,754, filed May 19, 2000, the entire disclosures of which are incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention concerns the treatment of cancers characterized by the overexpression of of a tumor antigen, such as an ErbB receptor, particularly HER2. More specifically, the invention concerns more effective treatment of human patients susceptible to or diagnosed with cancer, in which the tumor cells overexpress ErbB as determined by a gene amplification assay, with an ErbB antagonist, e.g., an anti-ErbB antibody. The invention further provides pharmaceutical packages for such treatment. BACKGROUND OF THE INVENTION [0003] Advancements in the understanding of genetics and developments in technology and epidemiology have allowed for the correlation of gen...

Claims

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Application Information

Patent Timeline
12 Oct 2006
Publication
US20060228745A1
IPC
C12Q1/68; G01N33/574; A61K39/395; A61K31/337; A61K45/00; A61K38/00; A61P35/00; A61P43/00; C07K16/32; C12Q1/6841; C12Q1/6886
CPC
A61K38/00; A61K39/39558; C07K16/32; C12Q1/6841; C12Q1/6886; C12Q2600/106; G01N33/5023; G01N33/57415
Inventors
MASS, ROBERT D.