Pertuzumab : evolving therapeutic strategies in the management of HER2-overexpressing breast cancer. [Review]
Pertuzumab : evolving therapeutic strategies in the management of HER2-overexpressing breast cancer. [Review]
- 2013
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.
English
1471-2598
*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]
Washington Cancer Institute
Journal Article
Research Support, Non-U.S. Gov't
Review
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.
English
1471-2598
*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]
Washington Cancer Institute
Journal Article
Research Support, Non-U.S. Gov't
Review