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 Reǵionālā 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.
Anticancer Drugs. 2013 Nov;24(10):1084-92. doi: 10.1097/CAD.0000000000000016.
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.
帕妥珠单抗是一种新型的抗人表皮生长因子受体 2（HER2）人源化单克隆抗体。在 III 期 CLEOPATRA 试验（NCT00567190）中，与曲妥珠单抗联合多西他赛相比，帕妥珠单抗联合曲妥珠单抗加多西他赛改善了 HER2 阳性转移性乳腺癌一线治疗的无进展生存期和总生存期。37 例患者参与了 CLEOPATRA 的药代动力学（PK）/校正 QT 间期亚研究，评估了潜在的 PK 药物相互作用（DDI）。采用非房室法计算 PK 参数，并进行 DDI 分析。在曲妥珠单抗和多西他赛存在的情况下，第 3 周期帕妥珠单抗的 Cmin 和 Cmax 分别为 63.6 和 183µg/ml。观察到的帕妥珠单抗浓度与验证的群体 PK 模型的模拟结果一致，表明曲妥珠单抗和多西他赛不会改变帕妥珠单抗的 PK。臂间几何最小二乘均数 PK 参数的比较表明，帕妥珠单抗对曲妥珠单抗或多西他赛的 PK 无影响。结论：当帕妥珠单抗、曲妥珠单抗和多西他赛联合用于治疗 HER2 阳性转移性乳腺癌时，未观察到 PK DDI。
