Pertuzumab : evolving therapeutic strategies in the management of HER2-overexpressing breast cancer. [Review]

MedStar author(s):
Citation: Expert Opinion on Biological Therapy. 13(5):779-90, 2013 May.PMID: 23530718Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, Non-U.S. Gov't | ReviewSubject headings: *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use] | *Breast Neoplasms/dt [Drug Therapy] | *Breast Neoplasms/ge [Genetics] | *Receptor, erbB-2/ge [Genetics] | Antibodies, Monoclonal, Humanized/ae [Adverse Effects] | Antibodies, Monoclonal, Humanized/pd [Pharmacology] | Antibodies, Monoclonal, Humanized/pk [Pharmacokinetics] | Clinical Trials, Phase I as Topic | Clinical Trials, Phase II as Topic | Clinical Trials, Phase III as Topic | Drug Approval | Drug Evaluation, Preclinical | Female | Gene Expression Regulation, Neoplastic | Humans | Neoadjuvant Therapy | Product Surveillance, Postmarketing | Receptor, erbB-2/me [Metabolism]Year: 2013ISSN:
  • 1471-2598
Name of journal: Expert opinion on biological therapyAbstract: AREAS COVERED: This article provides an overview of preclinical investigations in addition to reviewing pertinent Phase I, Phase II and Phase III clinical trials.EXPERT OPINION: Pertuzumab, in combination with the humanized monoclonal antibody trastuzumab, and docetaxel is a standard of care for patients with previously untreated metastatic breast cancer based on the CLEOPATRA study showing a survival benefit. There is no increase in cardiac toxicity with the combined HER2-targeted therapy. Future issues will address appropriate sequencing and combination with other anti-HER2-targeted therapies and/or chemotherapy.INTRODUCTION: HER2 overexpression or amplification is present in approximately one-fifth of breast cancers and historically was associated with aggressive disease and poorer prognosis. The introduction of the humanized monoclonal antibody trastuzumab dramatically improved disease-free survival (DFS) and overall survival (OS) in this subgroup. As the majority of patients with metastatic disease ultimately develop resistance to trastuzumab, a need exists for more effective targeted therapies. Pertuzumab is an anti-HER2/neu-targeted therapy in the late stages of clinical development. The combination of pertuzumab, trastuzumab and docetaxel has been found to have an OS benefit in patients with HER2 positive metastatic breast cancer (MBC) when used in the first-line setting. This reflects a new standard of care, and pertuzumab was recently approved for this indication by the Food and Drug Administration (FDA). The efficacy of pertuzumab and trastuzumab in conjunction with chemotherapy is currently being evaluated in the adjuvant setting.All authors: O'Sullivan CC, Swain SMFiscal year: FY2013Digital Object Identifier: Date added to catalog: 2013-12-24
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Journal Article MedStar Authors Catalog Article 23530718 Available 23530718

AREAS COVERED: This article provides an overview of preclinical investigations in addition to reviewing pertinent Phase I, Phase II and Phase III clinical trials.

EXPERT OPINION: Pertuzumab, in combination with the humanized monoclonal antibody trastuzumab, and docetaxel is a standard of care for patients with previously untreated metastatic breast cancer based on the CLEOPATRA study showing a survival benefit. There is no increase in cardiac toxicity with the combined HER2-targeted therapy. Future issues will address appropriate sequencing and combination with other anti-HER2-targeted therapies and/or chemotherapy.

INTRODUCTION: HER2 overexpression or amplification is present in approximately one-fifth of breast cancers and historically was associated with aggressive disease and poorer prognosis. The introduction of the humanized monoclonal antibody trastuzumab dramatically improved disease-free survival (DFS) and overall survival (OS) in this subgroup. As the majority of patients with metastatic disease ultimately develop resistance to trastuzumab, a need exists for more effective targeted therapies. Pertuzumab is an anti-HER2/neu-targeted therapy in the late stages of clinical development. The combination of pertuzumab, trastuzumab and docetaxel has been found to have an OS benefit in patients with HER2 positive metastatic breast cancer (MBC) when used in the first-line setting. This reflects a new standard of care, and pertuzumab was recently approved for this indication by the Food and Drug Administration (FDA). The efficacy of pertuzumab and trastuzumab in conjunction with chemotherapy is currently being evaluated in the adjuvant setting.

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