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.