Exposure-toxicity associations
Associations were found between palbociclib steady state pharmacokinetic variables and neutropenia. Higher values of palbociclib steady state Cmax and AUC0-24h were associated with severe (grade 3 or 4) neutropenia (p-values = 0.014 and 0.009, respectively). The odds ratio estimates (95% Wald confidence) were 7.49 (1.50-37.46) and 1.16 (1.04-1.30), respectively. In addition, associations were found between palbociclib pharmacokinetic variables and leukopenia. Higher values of single-dose palbociclib AUC0-48h, and steady state Cmax and AUC0-24h were associated with severe leukopenia (p-values = 0.038, 0.044 and 0.036, respectively). The odds ratio estimates were 1.10 (1.01-1.20), 3.95 (1.04-15.0) and 1.10 (1.01-1.19), respectively. No association was found between palbociclib pharmacokinetic variables and thrombocytopenia or lymphopenia.