Pharmacodynamic analysis of eribulin safety in breast cancer patients using real-world postmarketing surveillance data
Artikel i vetenskaplig tidskrift, 2018

Postmarketing surveillance is useful to collect safety data in real-world clinical settings. In this study, we applied postmarketing real-world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin-treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony-stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h−1, neutrophil elimination rate constant = 0.0295 h−1, and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model-based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin.




postmarketing surveillance



Takahisa Kawamura

Shizuoka Cancer Center

Keio University School of Medicine

Hidefumi Kasai

Certara USA, Inc.

Valentina Fermanelli

Keio University School of Medicine

Göteborgs universitet

Chalmers, Matematiska vetenskaper, Analys och sannolikhetsteori

Toshiaki Takahashi

Shizuoka Cancer Center

Yukinori Sakata

Eisai Co., Ltd.

Toshiyuki Matsuoka

Eisai Co., Ltd.

Mika Ishii

Eisai Co., Ltd.

Yusuke Tanigawara

Keio University School of Medicine

Cancer Science

1347-9032 (ISSN) 1349-7006 (eISSN)

Vol. 109 9 2822-2829


Farmaceutisk vetenskap

Urologi och njurmedicin

Cancer och onkologi



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