title: 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: aVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain bMedStar Washington Hospital Center, Washington Cancer Institute, Washington, District of Columbia cMid Ohio Oncology/Hematology Inc., The Mark H. Zangmeister Center, Columbus, Ohio dGenentech, South San Francisco, California eMemorial Sloan-Kettering Cancer Center, New York, New York, USA fRiga East University Hospital Oncology Center, Riga, Latvia gDaugavpils Re&gacute;ionālā Slimnīca, Daugavpils, Latvia hGesundheitszentrum Fricktal, Spital Rheinfelden & Laufenburg, Rheinfelden, Switzerland iNational Hospital Organization Osaka National Hospital, Osaka-City, Osaka, Japan jRoche Products Limited, Welwyn Garden City, UK kPharsight, Montreal, Quebec, Canada.
authors: Javier
authors: J
authors: Cortés
authors: Sandra M
authors: SM
authors: Swain
authors: Iveta
authors: I
authors: Kudaba
authors: Maik
authors: M
authors: Hauschild
authors: Taral
authors: T
authors: Patel
authors: Elza
authors: E
authors: Grincuka
authors: Norikazu
authors: N
authors: Masuda
authors: Virginia
authors: V
authors: McNally
authors: Graham
authors: G
authors: Ross
authors: Mike
authors: M
authors: Brewster
authors: Jean-François
authors: JF
authors: Marier
authors: My My
authors: MM
authors: Trinh
authors: Amit
authors: A
authors: Garg
authors: Ihsan
authors: I
authors: Nijem
authors: Jennifer
authors: J
authors: Visich
authors: Bert L
authors: BL
authors: Lum
authors: José
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authors: Baselga
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab