Impact of Abemaciclib-Induced Serum Creatinine Elevation on Dose Adjustment of Concomitant Medications

Abemaciclib (ABE) is a selective cyclin-dependent kinase 4/6 inhibitor widely used in breast cancer treatment. ABE inhibits renal tubular transporters, such as organic cation transporter 2, multidrug and toxin extrusion protein (MATE) 1, and MATE2-K, thereby suppressing creatinine excretion. This leads to a reversible increase in serum creatinine (Scr) without causing true renal injury. Since Scr is commonly used to assess renal function and guide medication dose adjustments, this effect may influence the management of concomitant renally excreted drugs. We aimed to evaluate the impact of ABE-induced Scr changes on the dosing of concomitant renally excreted medications in real-world clinical practice.

In this retrospective observational study, we included female patients who initiated ABE at Hokkaido Cancer Center between March 1, 2018, and March 31, 2023. Renal function was classified based on the Kidney Disease: Improving Global Outcomes guidelines, using creatinine clearance (CCr) cutoff values of 60 mL/min and 30 mL/min. The primary endpoint was the proportion of patients whose renal function classification changed post-ABE initiation, based on the lowest CCr value recorded during treatment.

Of 221 patients included in this study, 30.8% had grade ≥2 Scr elevation at 1 month post-ABE initiation, increasing to 56.6% after 2 years. CCr significantly decreased after ABE initiation compared with that at baseline (median [interquartile range]: 44.5 [34.7-55.7] mL/min vs. 61.6 [49.3-81.1] mL/min, p < 0.01). After ABE discontinuation, CCr values returned to baseline levels. Overall, 50.2% of patients experienced a change in renal function classification after ABE initiation (p < 0.01), and 22.6% required dose adjustment owing to these changes.

ABE administration led to Scr elevation and changes in renal function classification in approximately half of patients, impacting dose adjustment of concomitant renally excreted medications. Therefore, appropriate management methods, including cystatin C-based renal evaluation, are necessary.