Prospective monitoring of plasma abemaciclib in breast cancer patients: associations with age and adverse events

Abstract

Purpose: Plasma abemaciclib concentrations vary among individuals, and their association with hematologic toxicity has been reported in real-world settings. The incidence of interstitial lung disease (ILD), a serious adverse event of abemaciclib, is higher in clinical practice than in clinical trials. Here, to assess the potential usefulness of abemaciclib concentration monitoring, we conducted a prospective exploratory study of the association between plasma abemaciclib concentration, age, and the occurrence of adverse events in breast cancer patients.

Methods: Patients with hormone receptor-positive breast cancer who initiated abemaciclib with endocrine therapy between December 2022 and May 2025 were included. Plasma abemaciclib concentrations were measured using liquid chromatography-tandem mass spectrometry, and adverse events of grade ≥ 3 or those leading to treatment interruption were identified.

Results: A total of 322 plasma samples from 23 patients were analyzed. The median age was 52 years (range: 34-79), including four aged ≥ 65. Thirteen had metastatic disease, and six out of ten completed two-year adjuvant therapy. During a median follow-up of 344 days (range: 29-732), ILD occurred in five patients (21.7%). Abemaciclib concentrations on day 15 of cycle 1 were significantly higher in patients with ILD than in those without (p = 0.005, Mann-Whitney U test). A positive correlation was observed between age and concentration on day 15 of cycle 1 (Pearson's correlation coefficient = 0.54, p = 0.008), with increased variability in older patients.

Conclusion: Abemaciclib concentrations tend to be higher in elderly patients and may be associated with increased risk of ILD. These findings support the potential usefulness of abemaciclib concentration monitoring from a safety perspective in real-world practice.

Keywords: Abemaciclib; Adverse events; Breast cancer; Interstitial lung disease; Therapeutic drug monitoring.