Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer

• Published in: American journal of health-system pharmacy Vol. 70; no. 18; pp. 1579 - 1587
• Main Authors: CHUNG, CLEMENT, LAM, MASHA S. H.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society of Health-System Pharmacists 15.09.2013; Copyright American Society of Health-System Pharmacists, Inc. All rights reserved; American Society of Health Pharmacists; Oxford University Press
• Subjects: Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - economics; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dosage and administration; Drug Costs; Drug therapy; Epidermal growth factor; Female; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Licensing, certification and accreditation; Mammary gland diseases; Medical sciences; Metastasis; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Pertuzumab; Receptor, ErbB-2 - genetics; Tumors; United States; Human; Breast disease; Breast cancer; Monoclonal antibody; Malignant tumor; Metastasis; Epidermal growth factor receptor; Immunomodulator; Mammary gland diseases; Growth factor receptor; Treatment; Pertuzumab; Advanced stage; Cancer
• ISSN: 1079-2082; 1535-2900
• DOI: 10.2146/ajhp120735

PURPOSEThe pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of pertuzumab in patients with metastatic human epidermal growth factor receptor type 2 (HER2)-positive breast cancer are reviewed. SUMMARYDisease progression in HER2-positive breast cancer is often due to resistance to or a lack of efficacy of trastuzumab-based anti-HER2 therapy. Pertuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug Administration for the first-line treatment of patients with metastatic HER2-positive breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Since pertuzumab binds to a different epitope than trastuzumab, combination therapy with pertuzumab and trastuzumab results in a more complete blockade of HER2 signaling than trastuzumab monotherapy. The efficacy of adding pertuzumab to trastuzumab–docetaxel dual therapy was demonstrated in a pivotal randomized multicenter Phase III trial, which showed a significant benefit in terms of progression-free survival, with improved overall survival, in favor of the triple therapy as an initial regimen in treatment-naive patients with metastatic HER2-positive breast cancer. The combination of pertuzumab and trastuzumab has been found to have a tolerable toxicity profile. As clinical trials of pertuzumab for adjuvant, neoadjuvant, and metastatic-disease treatment continue, its role in the treatment of HER2-positive breast cancer will continue to evolve. CONCLUSIONPertuzumab, a novel HER2 dimerization inhibitor, has been shown to be effective in the treatment of metastatic HER2-positive breast cancer when used in combination with trastuzumab and docetaxel and is recommended for first-line therapy.