Population Pharmacokinetics of PF-05280014 (A Trastuzumab Biosimilar) and Reference Trastuzumab (Herceptin®) in Patients with HER2-Positive Metastatic Breast Cancer

The biosimilar to trastuzumab, PF-05280014, possesses similar pharmacokinetic (PK) parameters and covariates in Japanese patients with HER2-positive metastatic breast cancer (mBC), according to a study published in Cancer Chemotherapy and Pharmacology.

The researchers of this study sought to demonstrate the PK similarity of PF-05280014 in healthy volunteers, and conducted a comparative clinical study in patients with HER2-positive mBC comparing the efficacy, safety and immunogenicity of the biosimilar and trastuzumab sourced from the EU (trastuzumab-EU), both in conjunction with paclitaxel. They treated 702 patients in total: PF-05280014 (n = 349) and trastuzumab-EU (n = 353).  The research team also gathered peak-and-trough serum drug concentration samples in selected doses following repeated intravenous (IV) administration of PF-05280014 or trastuzumab-EU.

The patient population PK analysis was performed with using nonlinear mixed effect modeling drug concentration–time data to cycle 17 for each compound.  Moreover, the researchers assessed potential baseline covariates which comprised circulating HER2 concentrations, body weight, Japanese race, Eastern Cooperative Oncology Group status, number of metastatic sites and antidrug antibody status.

Results of the study showed that concentration–time data of PF-05280014 and trastuzumab-EU were adequately described by a two-compartment model with first-order elimination, inter-individual variability (IIV) on clearance (CL), volumes of distribution in central compartment (V1) as well as peripheral compartments, and intercompartment clearance. Furthermore, the study showed that similar estimated PK parameters and IIV were obtained for both treatments. Additionally, for PF-05280014 and trastuzumab-EU, baseline body weight was an influential covariate on CL and V1; the magnitude was comparable between treatments.

The study authors wrote that “PK was consistent between the limited number of Japanese and non-Japanese patients for both compounds and added that “these results provided further evidence in patients for PK similarity between PF-05280014 and trastuzumab-EU.”