Exposure-response analysis using time-to-event data for bevacizumab biosimilar SB8 and the reference bevacizumab.
Journal:
Frontiers in pharmacology
Published Date:
Jan 16, 2024
Abstract
This analysis aimed to characterize the exposure-response relationship of bevacizumab in non-small-cell lung cancer (NSCLC) and evaluate the efficacy of SB8, a bevacizumab biosimilar, and Avastin, the reference bevacizumab sourced from the European Union (EU), based on the exposure reported in a comparative phase III efficacy and safety study (EudraCT, 2015-004026-34; NCT02754882). The overall survival (OS) and progression-free survival (PFS) data from 224 patients with steady-state trough concentrations (C) were analyzed. A parametric time-to-event (TTE) model was developed using NONMEM, and the effects of treatments (SB8 and bevacizumab-EU) and patient demographic and clinical covariates on OS and PFS were evaluated. Simulations of median OS and PFS by bevacizumab C were conducted, and concentrations required to achieve 50% and 90% of the maximum median TTE were computed. A log-logistics model with C best described the OS and PFS data. Treatment was not a predictor of the hazard for OS or PFS. Simulations revealed steep exposure-response curves with a phase of rapid rise before saturating to a plateau. The median C values of SB8 and bevacizumab-EU reported from the clinical study were on the plateaus of the exposure-response curves. The concentrations required to achieve 50% and 90% of the maximum effect were 82.4 and 92.2 μg/mL, respectively, for OS and 79.7 and 89.1 μg/mL, respectively, for PFS. Simulations based on the constructed TTE models for OS and PFS have well described the exposure-response relationship of bevacizumab in advanced NSCLC. The analysis demonstrated comparable efficacy between SB8 and bevacizumab-EU in terms of OS and PFS based on their exposure levels.
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