Absence of pharmacokinetic drug-drug interaction of pertuzumab with trastuzumab and docetaxel.

Abstract

Pertuzumab is a novel antihuman epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody. Combined with trastuzumab plus docetaxel, pertuzumab improved progression-free and overall survival versus trastuzumab plus docetaxel in the phase III CLEOPATRA trial (NCT00567190) in first-line HER2-positive metastatic breast cancer. Thirty-seven patients participated in a pharmacokinetic (PK)/corrected QT interval substudy of CLEOPATRA, which evaluated potential PK drug-drug interaction (DDI). PK parameters were calculated using noncompartmental methods, and DDI analyses were carried out. In the presence of trastuzumab and docetaxel, the mean pertuzumab Cmin and Cmax in cycle 3 were 63.6 and 183 µg/ml, respectively. The pertuzumab concentrations observed were consistent with simulations from a validated population PK model, indicating that trastuzumab and docetaxel did not alter pertuzumab PK. Comparison of geometric least-squares mean PK parameters between arms showed no impact of pertuzumab on the PK of trastuzumab or docetaxel. In conclusion, no PK DDI was observed when pertuzumab, trastuzumab, and docetaxel were combined for the treatment of HER2-positive metastatic breast cancer.

• Authors: Javier Cortés, Sandra M Swain, Iveta Kudaba, Maik Hauschild, Taral Patel, Elza Grincuka, Norikazu Masuda, Virginia McNally, Graham Ross, Mike Brewster, Jean-François Marier, My My Trinh, Amit Garg, Ihsan Nijem, Jennifer Visich, Bert L Lum, José Baselga
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 24 Issue 10 Pg. 1084-92 (Nov 2013) ISSN: 1473-5741 [Electronic] England
• PMID: 23969513 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Taxoids
• Docetaxel
• ERBB2 protein, human
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, blood, pharmacokinetics, therapeutic use)
• Breast Neoplasms (blood, drug therapy, metabolism, pathology)
• Docetaxel
• Drug Administration Schedule
• Drug Interactions
• Female
• Humans
• Middle Aged
• Models, Biological
• Neoplasm Metastasis
• Receptor, ErbB-2 (metabolism)
• Taxoids (administration & dosage, pharmacokinetics, therapeutic use)
• Trastuzumab