Absence of pharmacokinetic drug-drug interaction of pertuzumab with trastuzumab and docetaxel.
Absence of pharmacokinetic drug-drug interaction of pertuzumab with trastuzumab and docetaxel.
- 2013
Available online from MWHC library: 2000 - present
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 g/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.
English
0959-4973
*Antibodies, Monoclonal, Humanized/pk [Pharmacokinetics]
*Antineoplastic Combined Chemotherapy Protocols/pk [Pharmacokinetics]
*Breast Neoplasms/dt [Drug Therapy]
*Taxoids/pk [Pharmacokinetics]
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Antibodies, Monoclonal, Humanized/bl [Blood]
Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
Antineoplastic Combined Chemotherapy Protocols/bl [Blood]
Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
Breast Neoplasms/bl [Blood]
Breast Neoplasms/me [Metabolism]
Breast Neoplasms/pa [Pathology]
Drug Administration Schedule
Drug Interactions
Female
Humans
Middle Aged
Models, Biological
Neoplasm Metastasis
Receptor, erbB-2/me [Metabolism]
Taxoids/ad [Administration & Dosage]
Taxoids/tu [Therapeutic Use]
Washington Cancer Institute
Journal Article
Research Support, Non-U.S. Gov't
Available online from MWHC library: 2000 - present
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 g/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.
English
0959-4973
*Antibodies, Monoclonal, Humanized/pk [Pharmacokinetics]
*Antineoplastic Combined Chemotherapy Protocols/pk [Pharmacokinetics]
*Breast Neoplasms/dt [Drug Therapy]
*Taxoids/pk [Pharmacokinetics]
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Antibodies, Monoclonal, Humanized/bl [Blood]
Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
Antineoplastic Combined Chemotherapy Protocols/bl [Blood]
Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
Breast Neoplasms/bl [Blood]
Breast Neoplasms/me [Metabolism]
Breast Neoplasms/pa [Pathology]
Drug Administration Schedule
Drug Interactions
Female
Humans
Middle Aged
Models, Biological
Neoplasm Metastasis
Receptor, erbB-2/me [Metabolism]
Taxoids/ad [Administration & Dosage]
Taxoids/tu [Therapeutic Use]
Washington Cancer Institute
Journal Article
Research Support, Non-U.S. Gov't