The mechanistical PBPK model consists of the base model for each TKI, lysosomal sequestration for the strong bases (afatinib and osimertinib), tumor immune deprivation, unaltered tumor perfusion, EGFR target binding and a more acidic extracellular water (i.e., water located just outside the tumor cells in the tumor microenvironment) in tumor tissue. Here, EGFR is linked to neoplasm.