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Quantitative Relationship Between AUEC of Absolute Neutrophil Count and Duration of Severe Neutropenia for G‐CSF in Breast Cancer Patients
Author(s) -
Li Liang,
Ma Lian,
Schrieber Sarah J.,
Rahman Nam Atiqur,
Deisseroth Albert,
Farrell Ann T.,
Wang Yaning,
Sinha Vikram,
Marathe Anshu
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.991
Subject(s) - filgrastim , medicine , absolute neutrophil count , neutropenia , breast cancer , count data , oncology , granulocyte colony stimulating factor , clinical trial , poisson regression , cancer , chemotherapy , poisson distribution , statistics , population , mathematics , environmental health
The aim of the study was to evaluate the quantitative relationship between duration of severe neutropenia (DSN, the efficacy endpoint) and area under effect curve of absolute neutrophil counts (ANC‐AUEC, the pharmacodynamic endpoint), based on data from filgrastim products, a human granulocyte colony‐stimulating factor (G‐CSF). Clinical data from filgrastim product comparator and test arms of two randomized, parallel‐group, phase III studies in breast cancer patients treated with myelosuppressive chemotherapy were utilized. A zero‐inflated Poisson regression model best described the negative correlation between DSN and ANC‐AUEC. The models predicted that with 10 × 10 9 day/L of increase in ANC‐AUEC, the mean DSN would decrease from 1.1 days to 0.93 day in Trial 1 and from 1.2 days to 1.0 day in Trial 2. The findings of the analysis provide useful information regarding the relationship between ANC and DSN that can be used for dose selection and optimization of clinical trial design for G‐CSF.