Abstract
Aim: The adverse events of the CKD4/6 inhibitor abemaciclib are known to
be dose dependent. However, its pharmacokinetics vary among individuals.
Abemaciclib is reported to be transported by P-glycoprotein (P-gp) and
the breast cancer resistance protein (BCRP). Therefore, we evaluated
whether ABCB1 and ABCG2 gene polymorphisms could be pharmacokinetic
predictive factors of abemaciclib. Methods: A total of 45 patients with
breast cancer able to take abemaciclib (150 mg twice daily) for 2 weeks
were evaluated to determine the association among abemaciclib
concentrations, adverse events, and ABCB1 1236T>C,
2677G>T/A, 3435C>T, and ABCG2
421C>A gene polymorphisms. Results: The trough
concentrations of abemaciclib were higher in the group with grade 2 or
greater neutropenia, anemia, and thrombocytopenia as compared with the
group with grades 0 or 1. No significant association was observed
between ABCB1 1236T>C, 3435C>T, and ABCG2
421C>A gene polymorphisms and abemaciclib concentrations.
However, in ABCB1 2677G>T/A polymorphisms, the
concentrations of abemaciclib tended to be higher in the homozygous
group (AA + AT) as compared with that in the wild-type and heterozygous
group (GG + GA + GT) [222.8 (80.5–295.8) ng/mL vs. 115.8
(23.6–355.2) ng/mL, P = 0.11]. Hence, the ABCB1
2677G>T/A homozygous group had a significantly higher
incidence of abemaciclib withdrawal and dose reduction within 4 weeks as
compared than the wild-type and heterozygous group (67% vs. 33%, P =
0.03). Conclusions: The gene polymorphism of ABCB1 2677G>
T/A might be a predictor of the pharmacokinetics and tolerability of
abemaciclib.