Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and Simulation Approach.

摘要: Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, pharmacokinetic-pharmacodynamic model was developed to describe time course of absolute neutrophil count (ANC) and quantify exposure-response relationship neutropenia. These analyses help understanding neutropenia associated its comparison chemotherapy-induced In model, plasma concentration related antiproliferative effect on precursor cells through drug-related parameters (ie, maximum estimated drug corresponding 50% effect), physiology mimicked system-related mean transit time, baseline ANC, feedback parameter). Sex albumin level were significant covariates ANC. It demonstrated by different evaluation approaches (eg, prediction-corrected visual predictive check standardized check) that final adequately described longitudinal ANC good capability. The established suggested higher exposure lower counts. nadir reached approximately 21 days after initiation. Consistent their mechanisms action, (cytostatic) rapidly reversible noncumulative, notably weaker relative chemotherapies (cytotoxic). This aids predicting optimizing dosing future trials regimen combinations.