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

IF 1.9 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2026-01-01 Epub Date: 2025-10-23 DOI:10.1159/000548669

Kengo Umehara, Yoshitaka Saito, Shinya Takada, Mitsugu Yamamoto, Nobumoto Tomioka, Kenichi Watanabe, Hiroyuki Kawaguchi

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引用次数: 0

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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阿贝马昔利诱发的血清肌酐升高对伴随用药剂量调整的影响。

Abemaciclib （ABE）是一种选择性细胞周期蛋白依赖性激酶4/6抑制剂，广泛用于乳腺癌治疗。ABE抑制肾小管转运蛋白如有机阳离子转运蛋白2、多药和毒素挤出蛋白（MATE） 1、MATE2-K，从而抑制肌酐排泄。这导致血清肌酐（Scr）可逆升高，而不引起真正的肾损伤。由于Scr通常用于评估肾功能和指导药物剂量调整，因此这种效应可能影响伴随肾排出药物的管理。我们的目的是评估在现实世界的临床实践中，abe诱导的Scr变化对伴随肾排泄药物剂量的影响。方法：在这项回顾性观察性研究中，我们纳入了2018年3月1日至2023年3月31日期间在北海道癌症中心接受ABE治疗的女性患者。肾功能根据肾脏疾病：改善全球结局指南进行分类，使用肌酐清除率（CCr）临界值为60 mL/min和30 mL/min。主要终点是基于治疗期间记录的最低CCr值，abe开始后肾功能分类改变的患者比例。结果：本研究纳入的221例患者中，30.8%的患者在abe启动后1个月Scr升高≥2级，2年后增加到56.6%。与基线相比，ABE启动后CCr显著降低（中位数[四分位数间距]:44.5 [34.7-55.7]mL/min vs. 61.6 [49.3-81.1] mL/min, P < 0.01）。停用ABE后，CCr值恢复到基线水平。总体而言，50.2%的患者在ABE开始后出现肾功能分级改变（P < 0.01）， 22.6%的患者因此需要调整剂量。结论：ABE给药导致约一半患者Scr升高和肾功能分级改变，影响了伴随肾排泄药物的剂量调整。因此，适当的管理方法是必要的，包括以胱抑素c为基础的肾脏评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.