Analyzing the distribution of progression-free survival for combination therapies: A study of model-based translational predictive methods in oncology
Journal article, 2024
In this paper, we analyze the distribution of PFS for a frequently used tumor growth inhibition model with and without drug-resistance and highlight the translational implications of this. Moreover, we explore and compare how the PFS distribution for combination therapy differs under the hypotheses of additive and independent-drug action.
Furthermore, we calibrate the model to preclinical data and use a previously calibrated clinical model to show that our analytical conclusions are applicable to real-world setting. Finally, we demonstrate that independent-drug action can effectively describe the tumor dynamics of patient-derived xenografts (PDXs) given certain drug combinations.
Oncology
Progression-free survival
Nonlinear mixed effects
Combination therapy
Author
Marcus Baaz
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Tim Cardilin
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Mats Jirstrand
Chalmers, Electrical Engineering, Systems and control
European Journal of Pharmaceutical Sciences
0928-0987 (ISSN) 1879-0720 (eISSN)
Vol. 203 106901Subject Categories
Mathematics
Computational Mathematics
Probability Theory and Statistics
DOI
10.1016/j.ejps.2024.106901